WorldWideScience

Sample records for large biological networks

  1. Querying Large Biological Network Datasets

    Science.gov (United States)

    Gulsoy, Gunhan

    2013-01-01

    New experimental methods has resulted in increasing amount of genetic interaction data to be generated every day. Biological networks are used to store genetic interaction data gathered. Increasing amount of data available requires fast large scale analysis methods. Therefore, we address the problem of querying large biological network datasets.…

  2. Impact of heuristics in clustering large biological networks.

    Science.gov (United States)

    Shafin, Md Kishwar; Kabir, Kazi Lutful; Ridwan, Iffatur; Anannya, Tasmiah Tamzid; Karim, Rashid Saadman; Hoque, Mohammad Mozammel; Rahman, M Sohel

    2015-12-01

    Traditional clustering algorithms often exhibit poor performance for large networks. On the contrary, greedy algorithms are found to be relatively efficient while uncovering functional modules from large biological networks. The quality of the clusters produced by these greedy techniques largely depends on the underlying heuristics employed. Different heuristics based on different attributes and properties perform differently in terms of the quality of the clusters produced. This motivates us to design new heuristics for clustering large networks. In this paper, we have proposed two new heuristics and analyzed the performance thereof after incorporating those with three different combinations in a recently celebrated greedy clustering algorithm named SPICi. We have extensively analyzed the effectiveness of these new variants. The results are found to be promising. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Comparing biological networks via graph compression

    Directory of Open Access Journals (Sweden)

    Hayashida Morihiro

    2010-09-01

    Full Text Available Abstract Background Comparison of various kinds of biological data is one of the main problems in bioinformatics and systems biology. Data compression methods have been applied to comparison of large sequence data and protein structure data. Since it is still difficult to compare global structures of large biological networks, it is reasonable to try to apply data compression methods to comparison of biological networks. In existing compression methods, the uniqueness of compression results is not guaranteed because there is some ambiguity in selection of overlapping edges. Results This paper proposes novel efficient methods, CompressEdge and CompressVertices, for comparing large biological networks. In the proposed methods, an original network structure is compressed by iteratively contracting identical edges and sets of connected edges. Then, the similarity of two networks is measured by a compression ratio of the concatenated networks. The proposed methods are applied to comparison of metabolic networks of several organisms, H. sapiens, M. musculus, A. thaliana, D. melanogaster, C. elegans, E. coli, S. cerevisiae, and B. subtilis, and are compared with an existing method. These results suggest that our methods can efficiently measure the similarities between metabolic networks. Conclusions Our proposed algorithms, which compress node-labeled networks, are useful for measuring the similarity of large biological networks.

  4. Communication on the structure of biological networks

    Indian Academy of Sciences (India)

    Introduction. Over the past few years, network science has drawn attention from a large number of ... The qualitative properties of biological networks cannot ... Here, we study the underlying undirected structure of empirical biological networks.

  5. Review of Biological Network Data and Its Applications

    Directory of Open Access Journals (Sweden)

    Donghyeon Yu

    2013-12-01

    Full Text Available Studying biological networks, such as protein-protein interactions, is key to understanding complex biological activities. Various types of large-scale biological datasets have been collected and analyzed with high-throughput technologies, including DNA microarray, next-generation sequencing, and the two-hybrid screening system, for this purpose. In this review, we focus on network-based approaches that help in understanding biological systems and identifying biological functions. Accordingly, this paper covers two major topics in network biology: reconstruction of gene regulatory networks and network-based applications, including protein function prediction, disease gene prioritization, and network-based genome-wide association study.

  6. Measuring the evolutionary rewiring of biological networks.

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    Chong Shou

    Full Text Available We have accumulated a large amount of biological network data and expect even more to come. Soon, we anticipate being able to compare many different biological networks as we commonly do for molecular sequences. It has long been believed that many of these networks change, or "rewire", at different rates. It is therefore important to develop a framework to quantify the differences between networks in a unified fashion. We developed such a formalism based on analogy to simple models of sequence evolution, and used it to conduct a systematic study of network rewiring on all the currently available biological networks. We found that, similar to sequences, biological networks show a decreased rate of change at large time divergences, because of saturation in potential substitutions. However, different types of biological networks consistently rewire at different rates. Using comparative genomics and proteomics data, we found a consistent ordering of the rewiring rates: transcription regulatory, phosphorylation regulatory, genetic interaction, miRNA regulatory, protein interaction, and metabolic pathway network, from fast to slow. This ordering was found in all comparisons we did of matched networks between organisms. To gain further intuition on network rewiring, we compared our observed rewirings with those obtained from simulation. We also investigated how readily our formalism could be mapped to other network contexts; in particular, we showed how it could be applied to analyze changes in a range of "commonplace" networks such as family trees, co-authorships and linux-kernel function dependencies.

  7. The effect of network biology on drug toxicology

    DEFF Research Database (Denmark)

    Gautier, Laurent; Taboureau, Olivier; Audouze, Karine Marie Laure

    2013-01-01

    Introduction: The high failure rate of drug candidates due to toxicity, during clinical trials, is a critical issue in drug discovery. Network biology has become a promising approach, in this regard, using the increasingly large amount of biological and chemical data available and combining...... it with bioinformatics. With this approach, the assessment of chemical safety can be done across multiple scales of complexity from molecular to cellular and system levels in human health. Network biology can be used at several levels of complexity. Areas covered: This review describes the strengths and limitations...... of network biology. The authors specifically assess this approach across different biological scales when it is applied to toxicity. Expert opinion: There has been much progress made with the amount of data that is generated by various omics technologies. With this large amount of useful data, network...

  8. Large Scale Proteomic Data and Network-Based Systems Biology Approaches to Explore the Plant World.

    Science.gov (United States)

    Di Silvestre, Dario; Bergamaschi, Andrea; Bellini, Edoardo; Mauri, PierLuigi

    2018-06-03

    The investigation of plant organisms by means of data-derived systems biology approaches based on network modeling is mainly characterized by genomic data, while the potential of proteomics is largely unexplored. This delay is mainly caused by the paucity of plant genomic/proteomic sequences and annotations which are fundamental to perform mass-spectrometry (MS) data interpretation. However, Next Generation Sequencing (NGS) techniques are contributing to filling this gap and an increasing number of studies are focusing on plant proteome profiling and protein-protein interactions (PPIs) identification. Interesting results were obtained by evaluating the topology of PPI networks in the context of organ-associated biological processes as well as plant-pathogen relationships. These examples foreshadow well the benefits that these approaches may provide to plant research. Thus, in addition to providing an overview of the main-omic technologies recently used on plant organisms, we will focus on studies that rely on concepts of module, hub and shortest path, and how they can contribute to the plant discovery processes. In this scenario, we will also consider gene co-expression networks, and some examples of integration with metabolomic data and genome-wide association studies (GWAS) to select candidate genes will be mentioned.

  9. Controllability and observability of Boolean networks arising from biology

    Science.gov (United States)

    Li, Rui; Yang, Meng; Chu, Tianguang

    2015-02-01

    Boolean networks are currently receiving considerable attention as a computational scheme for system level analysis and modeling of biological systems. Studying control-related problems in Boolean networks may reveal new insights into the intrinsic control in complex biological systems and enable us to develop strategies for manipulating biological systems using exogenous inputs. This paper considers controllability and observability of Boolean biological networks. We propose a new approach, which draws from the rich theory of symbolic computation, to solve the problems. Consequently, simple necessary and sufficient conditions for reachability, controllability, and observability are obtained, and algorithmic tests for controllability and observability which are based on the Gröbner basis method are presented. As practical applications, we apply the proposed approach to several different biological systems, namely, the mammalian cell-cycle network, the T-cell activation network, the large granular lymphocyte survival signaling network, and the Drosophila segment polarity network, gaining novel insights into the control and/or monitoring of the specific biological systems.

  10. Towards the understanding of network information processing in biology

    Science.gov (United States)

    Singh, Vijay

    Living organisms perform incredibly well in detecting a signal present in the environment. This information processing is achieved near optimally and quite reliably, even though the sources of signals are highly variable and complex. The work in the last few decades has given us a fair understanding of how individual signal processing units like neurons and cell receptors process signals, but the principles of collective information processing on biological networks are far from clear. Information processing in biological networks, like the brain, metabolic circuits, cellular-signaling circuits, etc., involves complex interactions among a large number of units (neurons, receptors). The combinatorially large number of states such a system can exist in makes it impossible to study these systems from the first principles, starting from the interactions between the basic units. The principles of collective information processing on such complex networks can be identified using coarse graining approaches. This could provide insights into the organization and function of complex biological networks. Here I study models of biological networks using continuum dynamics, renormalization, maximum likelihood estimation and information theory. Such coarse graining approaches identify features that are essential for certain processes performed by underlying biological networks. We find that long-range connections in the brain allow for global scale feature detection in a signal. These also suppress the noise and remove any gaps present in the signal. Hierarchical organization with long-range connections leads to large-scale connectivity at low synapse numbers. Time delays can be utilized to separate a mixture of signals with temporal scales. Our observations indicate that the rules in multivariate signal processing are quite different from traditional single unit signal processing.

  11. Reconstructing Causal Biological Networks through Active Learning.

    Directory of Open Access Journals (Sweden)

    Hyunghoon Cho

    Full Text Available Reverse-engineering of biological networks is a central problem in systems biology. The use of intervention data, such as gene knockouts or knockdowns, is typically used for teasing apart causal relationships among genes. Under time or resource constraints, one needs to carefully choose which intervention experiments to carry out. Previous approaches for selecting most informative interventions have largely been focused on discrete Bayesian networks. However, continuous Bayesian networks are of great practical interest, especially in the study of complex biological systems and their quantitative properties. In this work, we present an efficient, information-theoretic active learning algorithm for Gaussian Bayesian networks (GBNs, which serve as important models for gene regulatory networks. In addition to providing linear-algebraic insights unique to GBNs, leading to significant runtime improvements, we demonstrate the effectiveness of our method on data simulated with GBNs and the DREAM4 network inference challenge data sets. Our method generally leads to faster recovery of underlying network structure and faster convergence to final distribution of confidence scores over candidate graph structures using the full data, in comparison to random selection of intervention experiments.

  12. Dominating biological networks.

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    Tijana Milenković

    Full Text Available Proteins are essential macromolecules of life that carry out most cellular processes. Since proteins aggregate to perform function, and since protein-protein interaction (PPI networks model these aggregations, one would expect to uncover new biology from PPI network topology. Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention. A debate remains open about whether network properties of "biologically central (BC" genes (i.e., their protein products, such as those involved in aging, cancer, infectious diseases, or signaling and drug-targeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network.To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease. We hypothesize that BC genes have a topologically central (TC role in the human PPI network. We propose two different concepts of topological centrality. We design a new centrality measure to capture complex wirings of proteins in the network that identifies as TC those proteins that reside in dense extended network neighborhoods. Also, we use the notion of domination and find dominating sets (DSs in the PPI network, i.e., sets of proteins such that every protein is either in the DS or is a neighbor of the DS. Clearly, a DS has a TC role, as it enables efficient communication between different network parts. We find statistically significant enrichment in BC genes of TC nodes and outperform the existing methods indicating that genes involved in key biological processes occupy topologically complex and dense regions of the network and correspond to its "spine" that connects all other network parts and can thus pass cellular signals efficiently throughout the network. To our knowledge, this is the first study that explores domination in the context of PPI networks.

  13. Network biology: Describing biological systems by complex networks. Comment on "Network science of biological systems at different scales: A review" by M. Gosak et al.

    Science.gov (United States)

    Jalili, Mahdi

    2018-03-01

    I enjoyed reading Gosak et al. review on analysing biological systems from network science perspective [1]. Network science, first started within Physics community, is now a mature multidisciplinary field of science with many applications ranging from Ecology to biology, medicine, social sciences, engineering and computer science. Gosak et al. discussed how biological systems can be modelled and described by complex network theory which is an important application of network science. Although there has been considerable progress in network biology over the past two decades, this is just the beginning and network science has a great deal to offer to biology and medical sciences.

  14. Synthetic biological networks

    International Nuclear Information System (INIS)

    Archer, Eric; Süel, Gürol M

    2013-01-01

    Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

  15. A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

    Science.gov (United States)

    Chen, Bor-Sen; Lin, Ying-Po

    2013-01-01

    Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental

  16. Characterizing Topology of Probabilistic Biological Networks.

    Science.gov (United States)

    Todor, Andrei; Dobra, Alin; Kahveci, Tamer

    2013-09-06

    Biological interactions are often uncertain events, that may or may not take place with some probability. Existing studies analyze the degree distribution of biological networks by assuming that all the given interactions take place under all circumstances. This strong and often incorrect assumption can lead to misleading results. Here, we address this problem and develop a sound mathematical basis to characterize networks in the presence of uncertain interactions. We develop a method that accurately describes the degree distribution of such networks. We also extend our method to accurately compute the joint degree distributions of node pairs connected by edges. The number of possible network topologies grows exponentially with the number of uncertain interactions. However, the mathematical model we develop allows us to compute these degree distributions in polynomial time in the number of interactions. It also helps us find an adequate mathematical model using maximum likelihood estimation. Our results demonstrate that power law and log-normal models best describe degree distributions for probabilistic networks. The inverse correlation of degrees of neighboring nodes shows that, in probabilistic networks, nodes with large number of interactions prefer to interact with those with small number of interactions more frequently than expected.

  17. On the origin of distribution patterns of motifs in biological networks

    Directory of Open Access Journals (Sweden)

    Lesk Arthur M

    2008-08-01

    Full Text Available Abstract Background Inventories of small subgraphs in biological networks have identified commonly-recurring patterns, called motifs. The inference that these motifs have been selected for function rests on the idea that their occurrences are significantly more frequent than random. Results Our analysis of several large biological networks suggests, in contrast, that the frequencies of appearance of common subgraphs are similar in natural and corresponding random networks. Conclusion Indeed, certain topological features of biological networks give rise naturally to the common appearance of the motifs. We therefore question whether frequencies of occurrences are reasonable evidence that the structures of motifs have been selected for their functional contribution to the operation of networks.

  18. Large-scale networks in engineering and life sciences

    CERN Document Server

    Findeisen, Rolf; Flockerzi, Dietrich; Reichl, Udo; Sundmacher, Kai

    2014-01-01

    This edited volume provides insights into and tools for the modeling, analysis, optimization, and control of large-scale networks in the life sciences and in engineering. Large-scale systems are often the result of networked interactions between a large number of subsystems, and their analysis and control are becoming increasingly important. The chapters of this book present the basic concepts and theoretical foundations of network theory and discuss its applications in different scientific areas such as biochemical reactions, chemical production processes, systems biology, electrical circuits, and mobile agents. The aim is to identify common concepts, to understand the underlying mathematical ideas, and to inspire discussions across the borders of the various disciplines.  The book originates from the interdisciplinary summer school “Large Scale Networks in Engineering and Life Sciences” hosted by the International Max Planck Research School Magdeburg, September 26-30, 2011, and will therefore be of int...

  19. Dense module enumeration in biological networks

    Science.gov (United States)

    Tsuda, Koji; Georgii, Elisabeth

    2009-12-01

    Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

  20. Dense module enumeration in biological networks

    International Nuclear Information System (INIS)

    Tsuda, Koji; Georgii, Elisabeth

    2009-01-01

    Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

  1. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach.

    Science.gov (United States)

    Li, Jun; Zhao, Patrick X

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/.

  2. Characterizing the topology of probabilistic biological networks.

    Science.gov (United States)

    Todor, Andrei; Dobra, Alin; Kahveci, Tamer

    2013-01-01

    Biological interactions are often uncertain events, that may or may not take place with some probability. This uncertainty leads to a massive number of alternative interaction topologies for each such network. The existing studies analyze the degree distribution of biological networks by assuming that all the given interactions take place under all circumstances. This strong and often incorrect assumption can lead to misleading results. In this paper, we address this problem and develop a sound mathematical basis to characterize networks in the presence of uncertain interactions. Using our mathematical representation, we develop a method that can accurately describe the degree distribution of such networks. We also take one more step and extend our method to accurately compute the joint-degree distributions of node pairs connected by edges. The number of possible network topologies grows exponentially with the number of uncertain interactions. However, the mathematical model we develop allows us to compute these degree distributions in polynomial time in the number of interactions. Our method works quickly even for entire protein-protein interaction (PPI) networks. It also helps us find an adequate mathematical model using MLE. We perform a comparative study of node-degree and joint-degree distributions in two types of biological networks: the classical deterministic networks and the more flexible probabilistic networks. Our results confirm that power-law and log-normal models best describe degree distributions for both probabilistic and deterministic networks. Moreover, the inverse correlation of degrees of neighboring nodes shows that, in probabilistic networks, nodes with large number of interactions prefer to interact with those with small number of interactions more frequently than expected. We also show that probabilistic networks are more robust for node-degree distribution computation than the deterministic ones. all the data sets used, the software

  3. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena

    2016-01-01

    The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

  4. Uncovering Biological Network Function via Graphlet Degree Signatures

    Directory of Open Access Journals (Sweden)

    Nataša Pržulj

    2008-01-01

    Full Text Available Motivation: Proteins are essential macromolecules of life and thus understanding their function is of great importance. The number of functionally unclassified proteins is large even for simple and well studied organisms such as baker’s yeast. Methods for determining protein function have shifted their focus from targeting specific proteins based solely on sequence homology to analyses of the entire proteome based on protein-protein interaction (PPI networks. Since proteins interact to perform a certain function, analyzing structural properties of PPI networks may provide useful clues about the biological function of individual proteins, protein complexes they participate in, and even larger subcellular machines.Results: We design a sensitive graph theoretic method for comparing local structures of node neighborhoods that demonstrates that in PPI networks, biological function of a node and its local network structure are closely related. The method summarizes a protein’s local topology in a PPI network into the vector of graphlet degrees called the signature of the protein and computes the signature similarities between all protein pairs. We group topologically similar proteins under this measure in a PPI network and show that these protein groups belong to the same protein complexes, perform the same biological functions, are localized in the same subcellular compartments, and have the same tissue expressions. Moreover, we apply our technique on a proteome-scale network data and infer biological function of yet unclassified proteins demonstrating that our method can provide valuable guidelines for future experimental research such as disease protein prediction.Availability: Data is available upon request.

  5. LARGE-SCALE TOPOLOGICAL PROPERTIES OF MOLECULAR NETWORKS.

    Energy Technology Data Exchange (ETDEWEB)

    MASLOV,S.SNEPPEN,K.

    2003-11-17

    Bio-molecular networks lack the top-down design. Instead, selective forces of biological evolution shape them from raw material provided by random events such as gene duplications and single gene mutations. As a result individual connections in these networks are characterized by a large degree of randomness. One may wonder which connectivity patterns are indeed random, while which arose due to the network growth, evolution, and/or its fundamental design principles and limitations? Here we introduce a general method allowing one to construct a random null-model version of a given network while preserving the desired set of its low-level topological features, such as, e.g., the number of neighbors of individual nodes, the average level of modularity, preferential connections between particular groups of nodes, etc. Such a null-model network can then be used to detect and quantify the non-random topological patterns present in large networks. In particular, we measured correlations between degrees of interacting nodes in protein interaction and regulatory networks in yeast. It was found that in both these networks, links between highly connected proteins are systematically suppressed. This effect decreases the likelihood of cross-talk between different functional modules of the cell, and increases the overall robustness of a network by localizing effects of deleterious perturbations. It also teaches us about the overall computational architecture of such networks and points at the origin of large differences in the number of neighbors of individual nodes.

  6. Modular analysis of biological networks.

    Science.gov (United States)

    Kaltenbach, Hans-Michael; Stelling, Jörg

    2012-01-01

    The analysis of complex biological networks has traditionally relied on decomposition into smaller, semi-autonomous units such as individual signaling pathways. With the increased scope of systems biology (models), rational approaches to modularization have become an important topic. With increasing acceptance of de facto modularity in biology, widely different definitions of what constitutes a module have sparked controversies. Here, we therefore review prominent classes of modular approaches based on formal network representations. Despite some promising research directions, several important theoretical challenges remain open on the way to formal, function-centered modular decompositions for dynamic biological networks.

  7. Limitations and tradeoffs in synchronization of large-scale networks with uncertain links

    Science.gov (United States)

    Diwadkar, Amit; Vaidya, Umesh

    2016-01-01

    The synchronization of nonlinear systems connected over large-scale networks has gained popularity in a variety of applications, such as power grids, sensor networks, and biology. Stochastic uncertainty in the interconnections is a ubiquitous phenomenon observed in these physical and biological networks. We provide a size-independent network sufficient condition for the synchronization of scalar nonlinear systems with stochastic linear interactions over large-scale networks. This sufficient condition, expressed in terms of nonlinear dynamics, the Laplacian eigenvalues of the nominal interconnections, and the variance and location of the stochastic uncertainty, allows us to define a synchronization margin. We provide an analytical characterization of important trade-offs between the internal nonlinear dynamics, network topology, and uncertainty in synchronization. For nearest neighbour networks, the existence of an optimal number of neighbours with a maximum synchronization margin is demonstrated. An analytical formula for the optimal gain that produces the maximum synchronization margin allows us to compare the synchronization properties of various complex network topologies. PMID:27067994

  8. RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry.

    Science.gov (United States)

    Kulka, Ulrike; Abend, Michael; Ainsbury, Elizabeth; Badie, Christophe; Barquinero, Joan Francesc; Barrios, Lleonard; Beinke, Christina; Bortolin, Emanuela; Cucu, Alexandra; De Amicis, Andrea; Domínguez, Inmaculada; Fattibene, Paola; Frøvig, Anne Marie; Gregoire, Eric; Guogyte, Kamile; Hadjidekova, Valeria; Jaworska, Alicja; Kriehuber, Ralf; Lindholm, Carita; Lloyd, David; Lumniczky, Katalin; Lyng, Fiona; Meschini, Roberta; Mörtl, Simone; Della Monaca, Sara; Monteiro Gil, Octávia; Montoro, Alegria; Moquet, Jayne; Moreno, Mercedes; Oestreicher, Ursula; Palitti, Fabrizio; Pantelias, Gabriel; Patrono, Clarice; Piqueret-Stephan, Laure; Port, Matthias; Prieto, María Jesus; Quintens, Roel; Ricoul, Michelle; Romm, Horst; Roy, Laurence; Sáfrány, Géza; Sabatier, Laure; Sebastià, Natividad; Sommer, Sylwester; Terzoudi, Georgia; Testa, Antonella; Thierens, Hubert; Turai, Istvan; Trompier, François; Valente, Marco; Vaz, Pedro; Voisin, Philippe; Vral, Anne; Woda, Clemens; Zafiropoulos, Demetre; Wojcik, Andrzej

    2017-01-01

    A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.

  9. Exploitation of complex network topology for link prediction in biological interactomes

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-06-01

    The network representation of the interactions between proteins and genes allows for a holistic perspective of the complex machinery underlying the living cell. However, the large number of interacting entities within the cell makes network construction a daunting and arduous task, prone to errors and missing information. Fortunately, the structure of biological networks is not different from that of other complex systems, such as social networks, the world-wide web or power grids, for which growth models have been proposed to better understand their structure and function. This means that we can design tools based on these models in order to exploit the topology of biological interactomes with the aim to construct more complete and reliable maps of the cell. In this work, we propose three novel and powerful approaches for the prediction of interactions in biological networks and conclude that it is possible to mine the topology of these complex system representations and produce reliable and biologically meaningful information that enriches the datasets to which we have access today.

  10. PyPathway: Python Package for Biological Network Analysis and Visualization.

    Science.gov (United States)

    Xu, Yang; Luo, Xiao-Chun

    2018-05-01

    Life science studies represent one of the biggest generators of large data sets, mainly because of rapid sequencing technological advances. Biological networks including interactive networks and human curated pathways are essential to understand these high-throughput data sets. Biological network analysis offers a method to explore systematically not only the molecular complexity of a particular disease but also the molecular relationships among apparently distinct phenotypes. Currently, several packages for Python community have been developed, such as BioPython and Goatools. However, tools to perform comprehensive network analysis and visualization are still needed. Here, we have developed PyPathway, an extensible free and open source Python package for functional enrichment analysis, network modeling, and network visualization. The network process module supports various interaction network and pathway databases such as Reactome, WikiPathway, STRING, and BioGRID. The network analysis module implements overrepresentation analysis, gene set enrichment analysis, network-based enrichment, and de novo network modeling. Finally, the visualization and data publishing modules enable users to share their analysis by using an easy web application. For package availability, see the first Reference.

  11. Identification of important nodes in directed biological networks: a network motif approach.

    Directory of Open Access Journals (Sweden)

    Pei Wang

    Full Text Available Identification of important nodes in complex networks has attracted an increasing attention over the last decade. Various measures have been proposed to characterize the importance of nodes in complex networks, such as the degree, betweenness and PageRank. Different measures consider different aspects of complex networks. Although there are numerous results reported on undirected complex networks, few results have been reported on directed biological networks. Based on network motifs and principal component analysis (PCA, this paper aims at introducing a new measure to characterize node importance in directed biological networks. Investigations on five real-world biological networks indicate that the proposed method can robustly identify actually important nodes in different networks, such as finding command interneurons, global regulators and non-hub but evolutionary conserved actually important nodes in biological networks. Receiver Operating Characteristic (ROC curves for the five networks indicate remarkable prediction accuracy of the proposed measure. The proposed index provides an alternative complex network metric. Potential implications of the related investigations include identifying network control and regulation targets, biological networks modeling and analysis, as well as networked medicine.

  12. Mapping change in large networks.

    Directory of Open Access Journals (Sweden)

    Martin Rosvall

    2010-01-01

    Full Text Available Change is a fundamental ingredient of interaction patterns in biology, technology, the economy, and science itself: Interactions within and between organisms change; transportation patterns by air, land, and sea all change; the global financial flow changes; and the frontiers of scientific research change. Networks and clustering methods have become important tools to comprehend instances of these large-scale structures, but without methods to distinguish between real trends and noisy data, these approaches are not useful for studying how networks change. Only if we can assign significance to the partitioning of single networks can we distinguish meaningful structural changes from random fluctuations. Here we show that bootstrap resampling accompanied by significance clustering provides a solution to this problem. To connect changing structures with the changing function of networks, we highlight and summarize the significant structural changes with alluvial diagrams and realize de Solla Price's vision of mapping change in science: studying the citation pattern between about 7000 scientific journals over the past decade, we find that neuroscience has transformed from an interdisciplinary specialty to a mature and stand-alone discipline.

  13. Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems.

    Science.gov (United States)

    Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com © The Author(s) 2015. Published by Oxford University Press.

  14. Network Analyses in Systems Biology: New Strategies for Dealing with Biological Complexity

    DEFF Research Database (Denmark)

    Green, Sara; Serban, Maria; Scholl, Raphael

    2018-01-01

    of biological networks using tools from graph theory to the application of dynamical systems theory to understand the behavior of complex biological systems. We show how network approaches support and extend traditional mechanistic strategies but also offer novel strategies for dealing with biological...... strategies? When and how can network and mechanistic approaches interact in productive ways? In this paper we address these questions by focusing on how biological networks are represented and analyzed in a diverse class of case studies. Our examples span from the investigation of organizational properties...

  15. Novel recurrent neural network for modelling biological networks: oscillatory p53 interaction dynamics.

    Science.gov (United States)

    Ling, Hong; Samarasinghe, Sandhya; Kulasiri, Don

    2013-12-01

    Understanding the control of cellular networks consisting of gene and protein interactions and their emergent properties is a central activity of Systems Biology research. For this, continuous, discrete, hybrid, and stochastic methods have been proposed. Currently, the most common approach to modelling accurate temporal dynamics of networks is ordinary differential equations (ODE). However, critical limitations of ODE models are difficulty in kinetic parameter estimation and numerical solution of a large number of equations, making them more suited to smaller systems. In this article, we introduce a novel recurrent artificial neural network (RNN) that addresses above limitations and produces a continuous model that easily estimates parameters from data, can handle a large number of molecular interactions and quantifies temporal dynamics and emergent systems properties. This RNN is based on a system of ODEs representing molecular interactions in a signalling network. Each neuron represents concentration change of one molecule represented by an ODE. Weights of the RNN correspond to kinetic parameters in the system and can be adjusted incrementally during network training. The method is applied to the p53-Mdm2 oscillation system - a crucial component of the DNA damage response pathways activated by a damage signal. Simulation results indicate that the proposed RNN can successfully represent the behaviour of the p53-Mdm2 oscillation system and solve the parameter estimation problem with high accuracy. Furthermore, we presented a modified form of the RNN that estimates parameters and captures systems dynamics from sparse data collected over relatively large time steps. We also investigate the robustness of the p53-Mdm2 system using the trained RNN under various levels of parameter perturbation to gain a greater understanding of the control of the p53-Mdm2 system. Its outcomes on robustness are consistent with the current biological knowledge of this system. As more

  16. Biological transportation networks: Modeling and simulation

    KAUST Repository

    Albi, Giacomo

    2015-09-15

    We present a model for biological network formation originally introduced by Cai and Hu [Adaptation and optimization of biological transport networks, Phys. Rev. Lett. 111 (2013) 138701]. The modeling of fluid transportation (e.g., leaf venation and angiogenesis) and ion transportation networks (e.g., neural networks) is explained in detail and basic analytical features like the gradient flow structure of the fluid transportation network model and the impact of the model parameters on the geometry and topology of network formation are analyzed. We also present a numerical finite-element based discretization scheme and discuss sample cases of network formation simulations.

  17. BiologicalNetworks 2.0 - an integrative view of genome biology data

    Directory of Open Access Journals (Sweden)

    Ponomarenko Julia

    2010-12-01

    Full Text Available Abstract Background A significant problem in the study of mechanisms of an organism's development is the elucidation of interrelated factors which are making an impact on the different levels of the organism, such as genes, biological molecules, cells, and cell systems. Numerous sources of heterogeneous data which exist for these subsystems are still not integrated sufficiently enough to give researchers a straightforward opportunity to analyze them together in the same frame of study. Systematic application of data integration methods is also hampered by a multitude of such factors as the orthogonal nature of the integrated data and naming problems. Results Here we report on a new version of BiologicalNetworks, a research environment for the integral visualization and analysis of heterogeneous biological data. BiologicalNetworks can be queried for properties of thousands of different types of biological entities (genes/proteins, promoters, COGs, pathways, binding sites, and other and their relations (interactions, co-expression, co-citations, and other. The system includes the build-pathways infrastructure for molecular interactions/relations and module discovery in high-throughput experiments. Also implemented in BiologicalNetworks are the Integrated Genome Viewer and Comparative Genomics Browser applications, which allow for the search and analysis of gene regulatory regions and their conservation in multiple species in conjunction with molecular pathways/networks, experimental data and functional annotations. Conclusions The new release of BiologicalNetworks together with its back-end database introduces extensive functionality for a more efficient integrated multi-level analysis of microarray, sequence, regulatory, and other data. BiologicalNetworks is freely available at http://www.biologicalnetworks.org.

  18. Biological transportation networks: Modeling and simulation

    KAUST Repository

    Albi, Giacomo; Artina, Marco; Foransier, Massimo; Markowich, Peter A.

    2015-01-01

    We present a model for biological network formation originally introduced by Cai and Hu [Adaptation and optimization of biological transport networks, Phys. Rev. Lett. 111 (2013) 138701]. The modeling of fluid transportation (e.g., leaf venation

  19. The Latin American Biological Dosimetry Network (LBDNet)

    International Nuclear Information System (INIS)

    Garcia, O.; Lamadrid, A.I.; Gonzalez, J.E.; Romero, I.; Mandina, T.; Di Giorgio, M.; Radl, A.; Taja, M.R.; Sapienza, C.E.; Deminge, M.M.; Fernandez Rearte, J.; Stuck Oliveira, M.; Valdivia, P.; Guerrero-Carbajal, C.; Arceo Maldonado, C.; Cortina Ramirez, G.E.; Espinoza, M.; Martinez-Lopez, W.; Di Tomasso, M.

    2016-01-01

    Biological Dosimetry is a necessary support for national radiation protection programmes and emergency response schemes. The Latin American Biological Dosimetry Network (LBDNet) was formally founded in 2007 to provide early biological dosimetry assistance in case of radiation emergencies in the Latin American Region. Here are presented the main topics considered in the foundational document of the network, which comprise: mission, partners, concept of operation, including the mechanism to request support for biological dosimetry assistance in the region, and the network capabilities. The process for network activation and the role of the coordinating laboratory during biological dosimetry emergency response is also presented. This information is preceded by historical remarks on biological dosimetry cooperation in Latin America. A summary of the main experimental and practical results already obtained by the LBDNet is also included. (authors)

  20. On the Interplay between the Evolvability and Network Robustness in an Evolutionary Biological Network: A Systems Biology Approach

    Science.gov (United States)

    Chen, Bor-Sen; Lin, Ying-Po

    2011-01-01

    In the evolutionary process, the random transmission and mutation of genes provide biological diversities for natural selection. In order to preserve functional phenotypes between generations, gene networks need to evolve robustly under the influence of random perturbations. Therefore, the robustness of the phenotype, in the evolutionary process, exerts a selection force on gene networks to keep network functions. However, gene networks need to adjust, by variations in genetic content, to generate phenotypes for new challenges in the network’s evolution, ie, the evolvability. Hence, there should be some interplay between the evolvability and network robustness in evolutionary gene networks. In this study, the interplay between the evolvability and network robustness of a gene network and a biochemical network is discussed from a nonlinear stochastic system point of view. It was found that if the genetic robustness plus environmental robustness is less than the network robustness, the phenotype of the biological network is robust in evolution. The tradeoff between the genetic robustness and environmental robustness in evolution is discussed from the stochastic stability robustness and sensitivity of the nonlinear stochastic biological network, which may be relevant to the statistical tradeoff between bias and variance, the so-called bias/variance dilemma. Further, the tradeoff could be considered as an antagonistic pleiotropic action of a gene network and discussed from the systems biology perspective. PMID:22084563

  1. Mining biological networks from full-text articles.

    Science.gov (United States)

    Czarnecki, Jan; Shepherd, Adrian J

    2014-01-01

    The study of biological networks is playing an increasingly important role in the life sciences. Many different kinds of biological system can be modelled as networks; perhaps the most important examples are protein-protein interaction (PPI) networks, metabolic pathways, gene regulatory networks, and signalling networks. Although much useful information is easily accessible in publicly databases, a lot of extra relevant data lies scattered in numerous published papers. Hence there is a pressing need for automated text-mining methods capable of extracting such information from full-text articles. Here we present practical guidelines for constructing a text-mining pipeline from existing code and software components capable of extracting PPI networks from full-text articles. This approach can be adapted to tackle other types of biological network.

  2. Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology

    Directory of Open Access Journals (Sweden)

    Jose A. Santiago

    2017-05-01

    Full Text Available Neurodegenerative diseases are rarely caused by a mutation in a single gene but rather influenced by a combination of genetic, epigenetic and environmental factors. Emerging high-throughput technologies such as RNA sequencing have been instrumental in deciphering the molecular landscape of neurodegenerative diseases, however, the interpretation of such large amounts of data remains a challenge. Network biology has become a powerful platform to integrate multiple omics data to comprehensively explore the molecular networks in the context of health and disease. In this review article, we highlight recent advances in network biology approaches with an emphasis in brain-networks that have provided insights into the molecular mechanisms leading to the most prevalent neurodegenerative diseases including Alzheimer’s (AD, Parkinson’s (PD and Huntington’s diseases (HD. We discuss how integrative approaches using multi-omics data from different tissues have been valuable for identifying biomarkers and therapeutic targets. In addition, we discuss the challenges the field of network medicine faces toward the translation of network-based findings into clinically actionable tools for personalized medicine applications.

  3. OWL Reasoning Framework over Big Biological Knowledge Network

    Science.gov (United States)

    Chen, Huajun; Chen, Xi; Gu, Peiqin; Wu, Zhaohui; Yu, Tong

    2014-01-01

    Recently, huge amounts of data are generated in the domain of biology. Embedded with domain knowledge from different disciplines, the isolated biological resources are implicitly connected. Thus it has shaped a big network of versatile biological knowledge. Faced with such massive, disparate, and interlinked biological data, providing an efficient way to model, integrate, and analyze the big biological network becomes a challenge. In this paper, we present a general OWL (web ontology language) reasoning framework to study the implicit relationships among biological entities. A comprehensive biological ontology across traditional Chinese medicine (TCM) and western medicine (WM) is used to create a conceptual model for the biological network. Then corresponding biological data is integrated into a biological knowledge network as the data model. Based on the conceptual model and data model, a scalable OWL reasoning method is utilized to infer the potential associations between biological entities from the biological network. In our experiment, we focus on the association discovery between TCM and WM. The derived associations are quite useful for biologists to promote the development of novel drugs and TCM modernization. The experimental results show that the system achieves high efficiency, accuracy, scalability, and effectivity. PMID:24877076

  4. Exploring biological network structure with clustered random networks

    Directory of Open Access Journals (Sweden)

    Bansal Shweta

    2009-12-01

    Full Text Available Abstract Background Complex biological systems are often modeled as networks of interacting units. Networks of biochemical interactions among proteins, epidemiological contacts among hosts, and trophic interactions in ecosystems, to name a few, have provided useful insights into the dynamical processes that shape and traverse these systems. The degrees of nodes (numbers of interactions and the extent of clustering (the tendency for a set of three nodes to be interconnected are two of many well-studied network properties that can fundamentally shape a system. Disentangling the interdependent effects of the various network properties, however, can be difficult. Simple network models can help us quantify the structure of empirical networked systems and understand the impact of various topological properties on dynamics. Results Here we develop and implement a new Markov chain simulation algorithm to generate simple, connected random graphs that have a specified degree sequence and level of clustering, but are random in all other respects. The implementation of the algorithm (ClustRNet: Clustered Random Networks provides the generation of random graphs optimized according to a local or global, and relative or absolute measure of clustering. We compare our algorithm to other similar methods and show that ours more successfully produces desired network characteristics. Finding appropriate null models is crucial in bioinformatics research, and is often difficult, particularly for biological networks. As we demonstrate, the networks generated by ClustRNet can serve as random controls when investigating the impacts of complex network features beyond the byproduct of degree and clustering in empirical networks. Conclusion ClustRNet generates ensembles of graphs of specified edge structure and clustering. These graphs allow for systematic study of the impacts of connectivity and redundancies on network function and dynamics. This process is a key step in

  5. Hierarchical thinking in network biology: the unbiased modularization of biochemical networks.

    Science.gov (United States)

    Papin, Jason A; Reed, Jennifer L; Palsson, Bernhard O

    2004-12-01

    As reconstructed biochemical reaction networks continue to grow in size and scope, there is a growing need to describe the functional modules within them. Such modules facilitate the study of biological processes by deconstructing complex biological networks into conceptually simple entities. The definition of network modules is often based on intuitive reasoning. As an alternative, methods are being developed for defining biochemical network modules in an unbiased fashion. These unbiased network modules are mathematically derived from the structure of the whole network under consideration.

  6. Network Reconstruction of Dynamic Biological Systems

    OpenAIRE

    Asadi, Behrang

    2013-01-01

    Inference of network topology from experimental data is a central endeavor in biology, since knowledge of the underlying signaling mechanisms a requirement for understanding biological phenomena. As one of the most important tools in bioinformatics area, development of methods to reconstruct biological networks has attracted remarkable attention in the current decade. Integration of different data types can lead to remarkable improvements in our ability to identify the connectivity of differe...

  7. Canadian Cytogenetic Emergency network (CEN) for biological dosimetry following radiological/nuclear accidents.

    Science.gov (United States)

    Miller, Susan M; Ferrarotto, Catherine L; Vlahovich, Slavica; Wilkins, Ruth C; Boreham, Douglas R; Dolling, Jo-Anna

    2007-07-01

    To test the ability of the cytogenetic emergency network (CEN) of laboratories, currently under development across Canada, to provide rapid biological dosimetry using the dicentric assay for triage assessment, that could be implemented in the event of a large-scale radiation/nuclear emergency. A workshop was held in May 2004 in Toronto, Canada, to introduce the concept of CEN and recruit clinical cytogenetic laboratories at hospitals across the country. Slides were prepared for dicentric assay analysis following in vitro irradiation of blood to a range of gamma-ray doses. A minimum of 50 metaphases per slide were analyzed by 41 people at 22 different laboratories to estimate the exposure level. Dose estimates were calculated based on a dose response curve generated at Health Canada. There were a total of 104 dose estimates and 96 (92.3%) of them fell within the expected range using triage scoring criteria. Half of the laboratories analyzed 50 metaphases in network were acceptable for emergency biological dosimetry. When this network is fully operational, it will be the first of its kind in Canada able to respond to radiological/nuclear emergencies by providing triage quality biological dosimetry for a large number of samples. This network represents an alternate expansion of existing international emergency biological dosimetry cytogenetic networks.

  8. BioNSi: A Discrete Biological Network Simulator Tool.

    Science.gov (United States)

    Rubinstein, Amir; Bracha, Noga; Rudner, Liat; Zucker, Noga; Sloin, Hadas E; Chor, Benny

    2016-08-05

    Modeling and simulation of biological networks is an effective and widely used research methodology. The Biological Network Simulator (BioNSi) is a tool for modeling biological networks and simulating their discrete-time dynamics, implemented as a Cytoscape App. BioNSi includes a visual representation of the network that enables researchers to construct, set the parameters, and observe network behavior under various conditions. To construct a network instance in BioNSi, only partial, qualitative biological data suffices. The tool is aimed for use by experimental biologists and requires no prior computational or mathematical expertise. BioNSi is freely available at http://bionsi.wix.com/bionsi , where a complete user guide and a step-by-step manual can also be found.

  9. The Latin American Biological Dosimetry Network (LBDNet).

    Science.gov (United States)

    García, O; Di Giorgio, M; Radl, A; Taja, M R; Sapienza, C E; Deminge, M M; Fernández Rearte, J; Stuck Oliveira, M; Valdivia, P; Lamadrid, A I; González, J E; Romero, I; Mandina, T; Guerrero-Carbajal, C; ArceoMaldonado, C; Cortina Ramírez, G E; Espinoza, M; Martínez-López, W; Di Tomasso, M

    2016-09-01

    Biological Dosimetry is a necessary support for national radiation protection programmes and emergency response schemes. The Latin American Biological Dosimetry Network (LBDNet) was formally founded in 2007 to provide early biological dosimetry assistance in case of radiation emergencies in the Latin American Region. Here are presented the main topics considered in the foundational document of the network, which comprise: mission, partners, concept of operation, including the mechanism to request support for biological dosimetry assistance in the region, and the network capabilities. The process for network activation and the role of the coordinating laboratory during biological dosimetry emergency response is also presented. This information is preceded by historical remarks on biological dosimetry cooperation in Latin America. A summary of the main experimental and practical results already obtained by the LBDNet is also included. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. A generic algorithm for layout of biological networks.

    Science.gov (United States)

    Schreiber, Falk; Dwyer, Tim; Marriott, Kim; Wybrow, Michael

    2009-11-12

    Biological networks are widely used to represent processes in biological systems and to capture interactions and dependencies between biological entities. Their size and complexity is steadily increasing due to the ongoing growth of knowledge in the life sciences. To aid understanding of biological networks several algorithms for laying out and graphically representing networks and network analysis results have been developed. However, current algorithms are specialized to particular layout styles and therefore different algorithms are required for each kind of network and/or style of layout. This increases implementation effort and means that new algorithms must be developed for new layout styles. Furthermore, additional effort is necessary to compose different layout conventions in the same diagram. Also the user cannot usually customize the placement of nodes to tailor the layout to their particular need or task and there is little support for interactive network exploration. We present a novel algorithm to visualize different biological networks and network analysis results in meaningful ways depending on network types and analysis outcome. Our method is based on constrained graph layout and we demonstrate how it can handle the drawing conventions used in biological networks. The presented algorithm offers the ability to produce many of the fundamental popular drawing styles while allowing the exibility of constraints to further tailor these layouts.

  11. Learning and coding in biological neural networks

    Science.gov (United States)

    Fiete, Ila Rani

    How can large groups of neurons that locally modify their activities learn to collectively perform a desired task? Do studies of learning in small networks tell us anything about learning in the fantastically large collection of neurons that make up a vertebrate brain? What factors do neurons optimize by encoding sensory inputs or motor commands in the way they do? In this thesis I present a collection of four theoretical works: each of the projects was motivated by specific constraints and complexities of biological neural networks, as revealed by experimental studies; together, they aim to partially address some of the central questions of neuroscience posed above. We first study the role of sparse neural activity, as seen in the coding of sequential commands in a premotor area responsible for birdsong. We show that the sparse coding of temporal sequences in the songbird brain can, in a network where the feedforward plastic weights must translate the sparse sequential code into a time-varying muscle code, facilitate learning by minimizing synaptic interference. Next, we propose a biologically plausible synaptic plasticity rule that can perform goal-directed learning in recurrent networks of voltage-based spiking neurons that interact through conductances. Learning is based on the correlation of noisy local activity with a global reward signal; we prove that this rule performs stochastic gradient ascent on the reward. Thus, if the reward signal quantifies network performance on some desired task, the plasticity rule provably drives goal-directed learning in the network. To assess the convergence properties of the learning rule, we compare it with a known example of learning in the brain. Song-learning in finches is a clear example of a learned behavior, with detailed available neurophysiological data. With our learning rule, we train an anatomically accurate model birdsong network that drives a sound source to mimic an actual zebrafinch song. Simulation and

  12. Nonlinear signaling on biological networks: The role of stochasticity and spectral clustering

    Science.gov (United States)

    Hernandez-Hernandez, Gonzalo; Myers, Jesse; Alvarez-Lacalle, Enrique; Shiferaw, Yohannes

    2017-03-01

    Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switchlike properties which are critical to their biological function. In this study we investigate how the properties of these signaling systems depend on the network architecture. Our main result is that these nonlinear networks exhibit bistability where the network activity can switch between states that correspond to a low and high activity level. We show that this bistable regime emerges at a critical coupling strength that is determined by the spectral structure of the network. In particular, the set of nodes that correspond to large components of the leading eigenvector of the adjacency matrix determines the onset of bistability. Above this transition the eigenvectors of the adjacency matrix determine a hierarchy of clusters, defined by its spectral properties, which are activated sequentially with increasing network activity. We argue further that the onset of bistability occurs either continuously or discontinuously depending upon whether the leading eigenvector is localized or delocalized. Finally, we show that at low network coupling stochastic transitions to the active branch are also driven by the set of nodes that contribute more strongly to the leading eigenvector. However, at high coupling, transitions are insensitive to network structure since the network can be activated by stochastic transitions of a few nodes. Thus this work identifies important features of biological signaling networks that may underlie their biological

  13. Knowledge-fused differential dependency network models for detecting significant rewiring in biological networks.

    Science.gov (United States)

    Tian, Ye; Zhang, Bai; Hoffman, Eric P; Clarke, Robert; Zhang, Zhen; Shih, Ie-Ming; Xuan, Jianhua; Herrington, David M; Wang, Yue

    2014-07-24

    Modeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context-specific and dynamic in nature. To systematically characterize the selectively activated regulatory components and mechanisms, modeling tools must be able to effectively distinguish significant rewiring from random background fluctuations. While differential networks cannot be constructed by existing knowledge alone, novel incorporation of prior knowledge into data-driven approaches can improve the robustness and biological relevance of network inference. However, the major unresolved roadblocks include: big solution space but a small sample size; highly complex networks; imperfect prior knowledge; missing significance assessment; and heuristic structural parameter learning. To address these challenges, we formulated the inference of differential dependency networks that incorporate both conditional data and prior knowledge as a convex optimization problem, and developed an efficient learning algorithm to jointly infer the conserved biological network and the significant rewiring across different conditions. We used a novel sampling scheme to estimate the expected error rate due to "random" knowledge. Based on that scheme, we developed a strategy that fully exploits the benefit of this data-knowledge integrated approach. We demonstrated and validated the principle and performance of our method using synthetic datasets. We then applied our method to yeast cell line and breast cancer microarray data and obtained biologically plausible results. The open-source R software package and the experimental data are freely available at http://www.cbil.ece.vt.edu/software.htm. Experiments on both synthetic and real data demonstrate the effectiveness of the knowledge-fused differential dependency network in revealing the statistically significant rewiring in biological

  14. Pythoscape: a framework for generation of large protein similarity networks.

    Science.gov (United States)

    Barber, Alan E; Babbitt, Patricia C

    2012-11-01

    Pythoscape is a framework implemented in Python for processing large protein similarity networks for visualization in other software packages. Protein similarity networks are graphical representations of sequence, structural and other similarities among proteins for which pairwise all-by-all similarity connections have been calculated. Mapping of biological and other information to network nodes or edges enables hypothesis creation about sequence-structure-function relationships across sets of related proteins. Pythoscape provides several options to calculate pairwise similarities for input sequences or structures, applies filters to network edges and defines sets of similar nodes and their associated data as single nodes (termed representative nodes) for compression of network information and output data or formatted files for visualization.

  15. Perturbation Biology: Inferring Signaling Networks in Cellular Systems

    Science.gov (United States)

    Miller, Martin L.; Gauthier, Nicholas P.; Jing, Xiaohong; Kaushik, Poorvi; He, Qin; Mills, Gordon; Solit, David B.; Pratilas, Christine A.; Weigt, Martin; Braunstein, Alfredo; Pagnani, Andrea; Zecchina, Riccardo; Sander, Chris

    2013-01-01

    We present a powerful experimental-computational technology for inferring network models that predict the response of cells to perturbations, and that may be useful in the design of combinatorial therapy against cancer. The experiments are systematic series of perturbations of cancer cell lines by targeted drugs, singly or in combination. The response to perturbation is quantified in terms of relative changes in the measured levels of proteins, phospho-proteins and cellular phenotypes such as viability. Computational network models are derived de novo, i.e., without prior knowledge of signaling pathways, and are based on simple non-linear differential equations. The prohibitively large solution space of all possible network models is explored efficiently using a probabilistic algorithm, Belief Propagation (BP), which is three orders of magnitude faster than standard Monte Carlo methods. Explicit executable models are derived for a set of perturbation experiments in SKMEL-133 melanoma cell lines, which are resistant to the therapeutically important inhibitor of RAF kinase. The resulting network models reproduce and extend known pathway biology. They empower potential discoveries of new molecular interactions and predict efficacious novel drug perturbations, such as the inhibition of PLK1, which is verified experimentally. This technology is suitable for application to larger systems in diverse areas of molecular biology. PMID:24367245

  16. Reconstruction of biological networks based on life science data integration.

    Science.gov (United States)

    Kormeier, Benjamin; Hippe, Klaus; Arrigo, Patrizio; Töpel, Thoralf; Janowski, Sebastian; Hofestädt, Ralf

    2010-10-27

    For the implementation of the virtual cell, the fundamental question is how to model and simulate complex biological networks. Therefore, based on relevant molecular database and information systems, biological data integration is an essential step in constructing biological networks. In this paper, we will motivate the applications BioDWH--an integration toolkit for building life science data warehouses, CardioVINEdb--a information system for biological data in cardiovascular-disease and VANESA--a network editor for modeling and simulation of biological networks. Based on this integration process, the system supports the generation of biological network models. A case study of a cardiovascular-disease related gene-regulated biological network is also presented.

  17. Networks in Cell Biology

    Science.gov (United States)

    Buchanan, Mark; Caldarelli, Guido; De Los Rios, Paolo; Rao, Francesco; Vendruscolo, Michele

    2010-05-01

    Introduction; 1. Network views of the cell Paolo De Los Rios and Michele Vendruscolo; 2. Transcriptional regulatory networks Sarath Chandra Janga and M. Madan Babu; 3. Transcription factors and gene regulatory networks Matteo Brilli, Elissa Calistri and Pietro Lió; 4. Experimental methods for protein interaction identification Peter Uetz, Björn Titz, Seesandra V. Rajagopala and Gerard Cagney; 5. Modeling protein interaction networks Francesco Rao; 6. Dynamics and evolution of metabolic networks Daniel Segré; 7. Hierarchical modularity in biological networks: the case of metabolic networks Erzsébet Ravasz Regan; 8. Signalling networks Gian Paolo Rossini; Appendix 1. Complex networks: from local to global properties D. Garlaschelli and G. Caldarelli; Appendix 2. Modelling the local structure of networks D. Garlaschelli and G. Caldarelli; Appendix 3. Higher-order topological properties S. Ahnert, T. Fink and G. Caldarelli; Appendix 4. Elementary mathematical concepts A. Gabrielli and G. Caldarelli; References.

  18. Reconstruction of biological networks based on life science data integration

    Directory of Open Access Journals (Sweden)

    Kormeier Benjamin

    2010-06-01

    Full Text Available For the implementation of the virtual cell, the fundamental question is how to model and simulate complex biological networks. Therefore, based on relevant molecular database and information systems, biological data integration is an essential step in constructing biological networks. In this paper, we will motivate the applications BioDWH - an integration toolkit for building life science data warehouses, CardioVINEdb - a information system for biological data in cardiovascular-disease and VANESA- a network editor for modeling and simulation of biological networks. Based on this integration process, the system supports the generation of biological network models. A case study of a cardiovascular-disease related gene-regulated biological network is also presented.

  19. Evaluation of gene association methods for coexpression network construction and biological knowledge discovery.

    Directory of Open Access Journals (Sweden)

    Sapna Kumari

    Full Text Available BACKGROUND: Constructing coexpression networks and performing network analysis using large-scale gene expression data sets is an effective way to uncover new biological knowledge; however, the methods used for gene association in constructing these coexpression networks have not been thoroughly evaluated. Since different methods lead to structurally different coexpression networks and provide different information, selecting the optimal gene association method is critical. METHODS AND RESULTS: In this study, we compared eight gene association methods - Spearman rank correlation, Weighted Rank Correlation, Kendall, Hoeffding's D measure, Theil-Sen, Rank Theil-Sen, Distance Covariance, and Pearson - and focused on their true knowledge discovery rates in associating pathway genes and construction coordination networks of regulatory genes. We also examined the behaviors of different methods to microarray data with different properties, and whether the biological processes affect the efficiency of different methods. CONCLUSIONS: We found that the Spearman, Hoeffding and Kendall methods are effective in identifying coexpressed pathway genes, whereas the Theil-sen, Rank Theil-Sen, Spearman, and Weighted Rank methods perform well in identifying coordinated transcription factors that control the same biological processes and traits. Surprisingly, the widely used Pearson method is generally less efficient, and so is the Distance Covariance method that can find gene pairs of multiple relationships. Some analyses we did clearly show Pearson and Distance Covariance methods have distinct behaviors as compared to all other six methods. The efficiencies of different methods vary with the data properties to some degree and are largely contingent upon the biological processes, which necessitates the pre-analysis to identify the best performing method for gene association and coexpression network construction.

  20. Node fingerprinting: an efficient heuristic for aligning biological networks.

    Science.gov (United States)

    Radu, Alex; Charleston, Michael

    2014-10-01

    With the continuing increase in availability of biological data and improvements to biological models, biological network analysis has become a promising area of research. An emerging technique for the analysis of biological networks is through network alignment. Network alignment has been used to calculate genetic distance, similarities between regulatory structures, and the effect of external forces on gene expression, and to depict conditional activity of expression modules in cancer. Network alignment is algorithmically complex, and therefore we must rely on heuristics, ideally as efficient and accurate as possible. The majority of current techniques for network alignment rely on precomputed information, such as with protein sequence alignment, or on tunable network alignment parameters, which may introduce an increased computational overhead. Our presented algorithm, which we call Node Fingerprinting (NF), is appropriate for performing global pairwise network alignment without precomputation or tuning, can be fully parallelized, and is able to quickly compute an accurate alignment between two biological networks. It has performed as well as or better than existing algorithms on biological and simulated data, and with fewer computational resources. The algorithmic validation performed demonstrates the low computational resource requirements of NF.

  1. Inferring hidden causal relations between pathway members using reduced Google matrix of directed biological networks

    Science.gov (United States)

    2018-01-01

    Signaling pathways represent parts of the global biological molecular network which connects them into a seamless whole through complex direct and indirect (hidden) crosstalk whose structure can change during development or in pathological conditions. We suggest a novel methodology, called Googlomics, for the structural analysis of directed biological networks using spectral analysis of their Google matrices, using parallels with quantum scattering theory, developed for nuclear and mesoscopic physics and quantum chaos. We introduce analytical “reduced Google matrix” method for the analysis of biological network structure. The method allows inferring hidden causal relations between the members of a signaling pathway or a functionally related group of genes. We investigate how the structure of hidden causal relations can be reprogrammed as a result of changes in the transcriptional network layer during cancerogenesis. The suggested Googlomics approach rigorously characterizes complex systemic changes in the wiring of large causal biological networks in a computationally efficient way. PMID:29370181

  2. Power Laws, Scale-Free Networks and Genome Biology

    CERN Document Server

    Koonin, Eugene V; Karev, Georgy P

    2006-01-01

    Power Laws, Scale-free Networks and Genome Biology deals with crucial aspects of the theoretical foundations of systems biology, namely power law distributions and scale-free networks which have emerged as the hallmarks of biological organization in the post-genomic era. The chapters in the book not only describe the interesting mathematical properties of biological networks but moves beyond phenomenology, toward models of evolution capable of explaining the emergence of these features. The collection of chapters, contributed by both physicists and biologists, strives to address the problems in this field in a rigorous but not excessively mathematical manner and to represent different viewpoints, which is crucial in this emerging discipline. Each chapter includes, in addition to technical descriptions of properties of biological networks and evolutionary models, a more general and accessible introduction to the respective problems. Most chapters emphasize the potential of theoretical systems biology for disco...

  3. Design principles in biological networks

    Science.gov (United States)

    Goyal, Sidhartha

    Much of biology emerges from networks of interactions. Even in a single bacterium such as Escherichia coli, there are hundreds of coexisting gene and protein networks. Although biological networks are the outcome of evolution, various physical and biological constraints limit their functional capacity. The focus of this thesis is to understand how functional constraints such as optimal growth in mircoorganisms and information flow in signaling pathways shape the metabolic network of bacterium E. coli and the quorum sensing network of marine bacterium Vibrio harveyi, respectively. Metabolic networks convert basic elemental sources into complex building-blocks eventually leading to cell's growth. Therefore, typically, metabolic pathways are often coupled both by the use of a common substrate and by stoichiometric utilization of their products for cell growth. We showed that such a coupled network with product-feedback inhibition may exhibit limit-cycle oscillations which arise via a Hopf bifurcation. Furthermore, we analyzed several representative metabolic modules and find that, in all cases, simple product-feedback inhibition allows nearly optimal growth, in agreement with the predicted growth-rate by the flux-balance analysis (FBA). Bacteria have fascinating and diverse social lives. They display coordinated group behaviors regulated by quorum sensing (QS) systems. The QS circuit of V. harveyi integrates and funnels different ecological information through a common phosphorelay cascade to a set of small regulatory RNAs (sRNAs) that enables collective behavior. We analyzed the signaling properties and information flow in the QS circuit, which provides a model for information flow in signaling networks more generally. A comparative study of post-transcriptional and conventional transcriptional regulation suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. Furthermore, we develop a new framework for analyzing signal

  4. A Multilevel Gamma-Clustering Layout Algorithm for Visualization of Biological Networks

    Science.gov (United States)

    Hruz, Tomas; Lucas, Christoph; Laule, Oliver; Zimmermann, Philip

    2013-01-01

    Visualization of large complex networks has become an indispensable part of systems biology, where organisms need to be considered as one complex system. The visualization of the corresponding network is challenging due to the size and density of edges. In many cases, the use of standard visualization algorithms can lead to high running times and poorly readable visualizations due to many edge crossings. We suggest an approach that analyzes the structure of the graph first and then generates a new graph which contains specific semantic symbols for regular substructures like dense clusters. We propose a multilevel gamma-clustering layout visualization algorithm (MLGA) which proceeds in three subsequent steps: (i) a multilevel γ-clustering is used to identify the structure of the underlying network, (ii) the network is transformed to a tree, and (iii) finally, the resulting tree which shows the network structure is drawn using a variation of a force-directed algorithm. The algorithm has a potential to visualize very large networks because it uses modern clustering heuristics which are optimized for large graphs. Moreover, most of the edges are removed from the visual representation which allows keeping the overview over complex graphs with dense subgraphs. PMID:23864855

  5. Large-scale simulations of plastic neural networks on neuromorphic hardware

    Directory of Open Access Journals (Sweden)

    James Courtney Knight

    2016-04-01

    Full Text Available SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Rather than using bespoke analog or digital hardware, the basic computational unit of a SpiNNaker system is a general-purpose ARM processor, allowing it to be programmed to simulate a wide variety of neuron and synapse models. This flexibility is particularly valuable in the study of biological plasticity phenomena. A recently proposed learning rule based on the Bayesian Confidence Propagation Neural Network (BCPNN paradigm offers a generic framework for modeling the interaction of different plasticity mechanisms using spiking neurons. However, it can be computationally expensive to simulate large networks with BCPNN learning since it requires multiple state variables for each synapse, each of which needs to be updated every simulation time-step. We discuss the trade-offs in efficiency and accuracy involved in developing an event-based BCPNN implementation for SpiNNaker based on an analytical solution to the BCPNN equations, and detail the steps taken to fit this within the limited computational and memory resources of the SpiNNaker architecture. We demonstrate this learning rule by learning temporal sequences of neural activity within a recurrent attractor network which we simulate at scales of up to 20000 neurons and 51200000 plastic synapses: the largest plastic neural network ever to be simulated on neuromorphic hardware. We also run a comparable simulation on a Cray XC-30 supercomputer system and find that, if it is to match the run-time of our SpiNNaker simulation, the super computer system uses approximately more power. This suggests that cheaper, more power efficient neuromorphic systems are becoming useful discovery tools in the study of plasticity in large-scale brain models.

  6. Integration of genomic information with biological networks using Cytoscape.

    Science.gov (United States)

    Bauer-Mehren, Anna

    2013-01-01

    Cytoscape is an open-source software for visualizing, analyzing, and modeling biological networks. This chapter explains how to use Cytoscape to analyze the functional effect of sequence variations in the context of biological networks such as protein-protein interaction networks and signaling pathways. The chapter is divided into five parts: (1) obtaining information about the functional effect of sequence variation in a Cytoscape readable format, (2) loading and displaying different types of biological networks in Cytoscape, (3) integrating the genomic information (SNPs and mutations) with the biological networks, and (4) analyzing the effect of the genomic perturbation onto the network structure using Cytoscape built-in functions. Finally, we briefly outline how the integrated data can help in building mathematical network models for analyzing the effect of the sequence variation onto the dynamics of the biological system. Each part is illustrated by step-by-step instructions on an example use case and visualized by many screenshots and figures.

  7. Microarray Data Processing Techniques for Genome-Scale Network Inference from Large Public Repositories.

    Science.gov (United States)

    Chockalingam, Sriram; Aluru, Maneesha; Aluru, Srinivas

    2016-09-19

    Pre-processing of microarray data is a well-studied problem. Furthermore, all popular platforms come with their own recommended best practices for differential analysis of genes. However, for genome-scale network inference using microarray data collected from large public repositories, these methods filter out a considerable number of genes. This is primarily due to the effects of aggregating a diverse array of experiments with different technical and biological scenarios. Here we introduce a pre-processing pipeline suitable for inferring genome-scale gene networks from large microarray datasets. We show that partitioning of the available microarray datasets according to biological relevance into tissue- and process-specific categories significantly extends the limits of downstream network construction. We demonstrate the effectiveness of our pre-processing pipeline by inferring genome-scale networks for the model plant Arabidopsis thaliana using two different construction methods and a collection of 11,760 Affymetrix ATH1 microarray chips. Our pre-processing pipeline and the datasets used in this paper are made available at http://alurulab.cc.gatech.edu/microarray-pp.

  8. [Network structures in biological systems].

    Science.gov (United States)

    Oleskin, A V

    2013-01-01

    Network structures (networks) that have been extensively studied in the humanities are characterized by cohesion, a lack of a central control unit, and predominantly fractal properties. They are contrasted with structures that contain a single centre (hierarchies) as well as with those whose elements predominantly compete with one another (market-type structures). As far as biological systems are concerned, their network structures can be subdivided into a number of types involving different organizational mechanisms. Network organization is characteristic of various structural levels of biological systems ranging from single cells to integrated societies. These networks can be classified into two main subgroups: (i) flat (leaderless) network structures typical of systems that are composed of uniform elements and represent modular organisms or at least possess manifest integral properties and (ii) three-dimensional, partly hierarchical structures characterized by significant individual and/or intergroup (intercaste) differences between their elements. All network structures include an element that performs structural, protective, and communication-promoting functions. By analogy to cell structures, this element is denoted as the matrix of a network structure. The matrix includes a material and an immaterial component. The material component comprises various structures that belong to the whole structure and not to any of its elements per se. The immaterial (ideal) component of the matrix includes social norms and rules regulating network elements' behavior. These behavioral rules can be described in terms of algorithms. Algorithmization enables modeling the behavior of various network structures, particularly of neuron networks and their artificial analogs.

  9. From biological and social network metaphors to coupled bio-social wireless networks

    Science.gov (United States)

    Barrett, Christopher L.; Eubank, Stephen; Anil Kumar, V.S.; Marathe, Madhav V.

    2010-01-01

    Biological and social analogies have been long applied to complex systems. Inspiration has been drawn from biological solutions to solve problems in engineering products and systems, ranging from Velcro to camouflage to robotics to adaptive and learning computing methods. In this paper, we present an overview of recent advances in understanding biological systems as networks and use this understanding to design and analyse wireless communication networks. We expand on two applications, namely cognitive sensing and control and wireless epidemiology. We discuss how our work in these two applications is motivated by biological metaphors. We believe that recent advances in computing and communications coupled with advances in health and social sciences raise the possibility of studying coupled bio-social communication networks. We argue that we can better utilise the advances in our understanding of one class of networks to better our understanding of the other. PMID:21643462

  10. Functional model of biological neural networks.

    Science.gov (United States)

    Lo, James Ting-Ho

    2010-12-01

    A functional model of biological neural networks, called temporal hierarchical probabilistic associative memory (THPAM), is proposed in this paper. THPAM comprises functional models of dendritic trees for encoding inputs to neurons, a first type of neuron for generating spike trains, a second type of neuron for generating graded signals to modulate neurons of the first type, supervised and unsupervised Hebbian learning mechanisms for easy learning and retrieving, an arrangement of dendritic trees for maximizing generalization, hardwiring for rotation-translation-scaling invariance, and feedback connections with different delay durations for neurons to make full use of present and past informations generated by neurons in the same and higher layers. These functional models and their processing operations have many functions of biological neural networks that have not been achieved by other models in the open literature and provide logically coherent answers to many long-standing neuroscientific questions. However, biological justifications of these functional models and their processing operations are required for THPAM to qualify as a macroscopic model (or low-order approximate) of biological neural networks.

  11. ProteoLens: a visual analytic tool for multi-scale database-driven biological network data mining.

    Science.gov (United States)

    Huan, Tianxiao; Sivachenko, Andrey Y; Harrison, Scott H; Chen, Jake Y

    2008-08-12

    New systems biology studies require researchers to understand how interplay among myriads of biomolecular entities is orchestrated in order to achieve high-level cellular and physiological functions. Many software tools have been developed in the past decade to help researchers visually navigate large networks of biomolecular interactions with built-in template-based query capabilities. To further advance researchers' ability to interrogate global physiological states of cells through multi-scale visual network explorations, new visualization software tools still need to be developed to empower the analysis. A robust visual data analysis platform driven by database management systems to perform bi-directional data processing-to-visualizations with declarative querying capabilities is needed. We developed ProteoLens as a JAVA-based visual analytic software tool for creating, annotating and exploring multi-scale biological networks. It supports direct database connectivity to either Oracle or PostgreSQL database tables/views, on which SQL statements using both Data Definition Languages (DDL) and Data Manipulation languages (DML) may be specified. The robust query languages embedded directly within the visualization software help users to bring their network data into a visualization context for annotation and exploration. ProteoLens supports graph/network represented data in standard Graph Modeling Language (GML) formats, and this enables interoperation with a wide range of other visual layout tools. The architectural design of ProteoLens enables the de-coupling of complex network data visualization tasks into two distinct phases: 1) creating network data association rules, which are mapping rules between network node IDs or edge IDs and data attributes such as functional annotations, expression levels, scores, synonyms, descriptions etc; 2) applying network data association rules to build the network and perform the visual annotation of graph nodes and edges

  12. Applying differential dynamic logic to reconfigurable biological networks.

    Science.gov (United States)

    Figueiredo, Daniel; Martins, Manuel A; Chaves, Madalena

    2017-09-01

    Qualitative and quantitative modeling frameworks are widely used for analysis of biological regulatory networks, the former giving a preliminary overview of the system's global dynamics and the latter providing more detailed solutions. Another approach is to model biological regulatory networks as hybrid systems, i.e., systems which can display both continuous and discrete dynamic behaviors. Actually, the development of synthetic biology has shown that this is a suitable way to think about biological systems, which can often be constructed as networks with discrete controllers, and present hybrid behaviors. In this paper we discuss this approach as a special case of the reconfigurability paradigm, well studied in Computer Science (CS). In CS there are well developed computational tools to reason about hybrid systems. We argue that it is worth applying such tools in a biological context. One interesting tool is differential dynamic logic (dL), which has recently been developed by Platzer and applied to many case-studies. In this paper we discuss some simple examples of biological regulatory networks to illustrate how dL can be used as an alternative, or also as a complement to methods already used. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Computing chemical organizations in biological networks.

    Science.gov (United States)

    Centler, Florian; Kaleta, Christoph; di Fenizio, Pietro Speroni; Dittrich, Peter

    2008-07-15

    Novel techniques are required to analyze computational models of intracellular processes as they increase steadily in size and complexity. The theory of chemical organizations has recently been introduced as such a technique that links the topology of biochemical reaction network models to their dynamical repertoire. The network is decomposed into algebraically closed and self-maintaining subnetworks called organizations. They form a hierarchy representing all feasible system states including all steady states. We present three algorithms to compute the hierarchy of organizations for network models provided in SBML format. Two of them compute the complete organization hierarchy, while the third one uses heuristics to obtain a subset of all organizations for large models. While the constructive approach computes the hierarchy starting from the smallest organization in a bottom-up fashion, the flux-based approach employs self-maintaining flux distributions to determine organizations. A runtime comparison on 16 different network models of natural systems showed that none of the two exhaustive algorithms is superior in all cases. Studying a 'genome-scale' network model with 762 species and 1193 reactions, we demonstrate how the organization hierarchy helps to uncover the model structure and allows to evaluate the model's quality, for example by detecting components and subsystems of the model whose maintenance is not explained by the model. All data and a Java implementation that plugs into the Systems Biology Workbench is available from http://www.minet.uni-jena.de/csb/prj/ot/tools.

  14. Organization of excitable dynamics in hierarchical biological networks.

    Directory of Open Access Journals (Sweden)

    Mark Müller-Linow

    Full Text Available This study investigates the contributions of network topology features to the dynamic behavior of hierarchically organized excitable networks. Representatives of different types of hierarchical networks as well as two biological neural networks are explored with a three-state model of node activation for systematically varying levels of random background network stimulation. The results demonstrate that two principal topological aspects of hierarchical networks, node centrality and network modularity, correlate with the network activity patterns at different levels of spontaneous network activation. The approach also shows that the dynamic behavior of the cerebral cortical systems network in the cat is dominated by the network's modular organization, while the activation behavior of the cellular neuronal network of Caenorhabditis elegans is strongly influenced by hub nodes. These findings indicate the interaction of multiple topological features and dynamic states in the function of complex biological networks.

  15. Application of random matrix theory to biological networks

    Energy Technology Data Exchange (ETDEWEB)

    Luo Feng [Department of Computer Science, Clemson University, 100 McAdams Hall, Clemson, SC 29634 (United States); Department of Pathology, U.T. Southwestern Medical Center, 5323 Harry Hines Blvd. Dallas, TX 75390-9072 (United States); Zhong Jianxin [Department of Physics, Xiangtan University, Hunan 411105 (China) and Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States)]. E-mail: zhongjn@ornl.gov; Yang Yunfeng [Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Scheuermann, Richard H. [Department of Pathology, U.T. Southwestern Medical Center, 5323 Harry Hines Blvd. Dallas, TX 75390-9072 (United States); Zhou Jizhong [Department of Botany and Microbiology, University of Oklahoma, Norman, OK 73019 (United States) and Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States)]. E-mail: zhouj@ornl.gov

    2006-09-25

    We show that spectral fluctuation of interaction matrices of a yeast protein-protein interaction network and a yeast metabolic network follows the description of the Gaussian orthogonal ensemble (GOE) of random matrix theory (RMT). Furthermore, we demonstrate that while the global biological networks evaluated belong to GOE, removal of interactions between constituents transitions the networks to systems of isolated modules described by the Poisson distribution. Our results indicate that although biological networks are very different from other complex systems at the molecular level, they display the same statistical properties at network scale. The transition point provides a new objective approach for the identification of functional modules.

  16. Probabilistic biological network alignment.

    Science.gov (United States)

    Todor, Andrei; Dobra, Alin; Kahveci, Tamer

    2013-01-01

    Interactions between molecules are probabilistic events. An interaction may or may not happen with some probability, depending on a variety of factors such as the size, abundance, or proximity of the interacting molecules. In this paper, we consider the problem of aligning two biological networks. Unlike existing methods, we allow one of the two networks to contain probabilistic interactions. Allowing interaction probabilities makes the alignment more biologically relevant at the expense of explosive growth in the number of alternative topologies that may arise from different subsets of interactions that take place. We develop a novel method that efficiently and precisely characterizes this massive search space. We represent the topological similarity between pairs of aligned molecules (i.e., proteins) with the help of random variables and compute their expected values. We validate our method showing that, without sacrificing the running time performance, it can produce novel alignments. Our results also demonstrate that our method identifies biologically meaningful mappings under a comprehensive set of criteria used in the literature as well as the statistical coherence measure that we developed to analyze the statistical significance of the similarity of the functions of the aligned protein pairs.

  17. Using Facebook Groups to Encourage Science Discussions in a Large-Enrollment Biology Class

    Science.gov (United States)

    Pai, Aditi; McGinnis, Gene; Bryant, Dana; Cole, Megan; Kovacs, Jennifer; Stovall, Kyndra; Lee, Mark

    2017-01-01

    This case study reports the instructional development, impact, and lessons learned regarding the use of Facebook as an educational tool within a large enrollment Biology class at Spelman College (Atlanta, GA). We describe the use of this social networking site to (a) engage students in active scientific discussions, (b) build community within the…

  18. Building gene co-expression networks using transcriptomics data for systems biology investigations

    DEFF Research Database (Denmark)

    Kadarmideen, Haja; Watson-Haigh, Nathan S.

    2012-01-01

    Gene co-expression networks (GCN), built using high-throughput gene expression data are fundamental aspects of systems biology. The main aims of this study were to compare two popular approaches to building and analysing GCN. We use real ovine microarray transcriptomics datasets representing four......) is connected within a network. The two GCN construction methods used were, Weighted Gene Co-expression Network Analysis (WGCNA) and Partial Correlation and Information Theory (PCIT) methods. Nodes were ranked based on their connectivity measures in each of the four different networks created by WGCNA and PCIT...... (with > 20000 genes) access to large computer clusters, particularly those with larger amounts of shared memory is recommended....

  19. An efficient grid layout algorithm for biological networks utilizing various biological attributes

    Directory of Open Access Journals (Sweden)

    Kato Mitsuru

    2007-03-01

    Full Text Available Abstract Background Clearly visualized biopathways provide a great help in understanding biological systems. However, manual drawing of large-scale biopathways is time consuming. We proposed a grid layout algorithm that can handle gene-regulatory networks and signal transduction pathways by considering edge-edge crossing, node-edge crossing, distance measure between nodes, and subcellular localization information from Gene Ontology. Consequently, the layout algorithm succeeded in drastically reducing these crossings in the apoptosis model. However, for larger-scale networks, we encountered three problems: (i the initial layout is often very far from any local optimum because nodes are initially placed at random, (ii from a biological viewpoint, human layouts still exceed automatic layouts in understanding because except subcellular localization, it does not fully utilize biological information of pathways, and (iii it employs a local search strategy in which the neighborhood is obtained by moving one node at each step, and automatic layouts suggest that simultaneous movements of multiple nodes are necessary for better layouts, while such extension may face worsening the time complexity. Results We propose a new grid layout algorithm. To address problem (i, we devised a new force-directed algorithm whose output is suitable as the initial layout. For (ii, we considered that an appropriate alignment of nodes having the same biological attribute is one of the most important factors of the comprehension, and we defined a new score function that gives an advantage to such configurations. For solving problem (iii, we developed a search strategy that considers swapping nodes as well as moving a node, while keeping the order of the time complexity. Though a naïve implementation increases by one order, the time complexity, we solved this difficulty by devising a method that caches differences between scores of a layout and its possible updates

  20. Large scale network-centric distributed systems

    CERN Document Server

    Sarbazi-Azad, Hamid

    2014-01-01

    A highly accessible reference offering a broad range of topics and insights on large scale network-centric distributed systems Evolving from the fields of high-performance computing and networking, large scale network-centric distributed systems continues to grow as one of the most important topics in computing and communication and many interdisciplinary areas. Dealing with both wired and wireless networks, this book focuses on the design and performance issues of such systems. Large Scale Network-Centric Distributed Systems provides in-depth coverage ranging from ground-level hardware issu

  1. Emergence of switch-like behavior in a large family of simple biochemical networks.

    Directory of Open Access Journals (Sweden)

    Dan Siegal-Gaskins

    2011-05-01

    Full Text Available Bistability plays a central role in the gene regulatory networks (GRNs controlling many essential biological functions, including cellular differentiation and cell cycle control. However, establishing the network topologies that can exhibit bistability remains a challenge, in part due to the exceedingly large variety of GRNs that exist for even a small number of components. We begin to address this problem by employing chemical reaction network theory in a comprehensive in silico survey to determine the capacity for bistability of more than 40,000 simple networks that can be formed by two transcription factor-coding genes and their associated proteins (assuming only the most elementary biochemical processes. We find that there exist reaction rate constants leading to bistability in ∼90% of these GRN models, including several circuits that do not contain any of the TF cooperativity commonly associated with bistable systems, and the majority of which could only be identified as bistable through an original subnetwork-based analysis. A topological sorting of the two-gene family of networks based on the presence or absence of biochemical reactions reveals eleven minimal bistable networks (i.e., bistable networks that do not contain within them a smaller bistable subnetwork. The large number of previously unknown bistable network topologies suggests that the capacity for switch-like behavior in GRNs arises with relative ease and is not easily lost through network evolution. To highlight the relevance of the systematic application of CRNT to bistable network identification in real biological systems, we integrated publicly available protein-protein interaction, protein-DNA interaction, and gene expression data from Saccharomyces cerevisiae, and identified several GRNs predicted to behave in a bistable fashion.

  2. Multilayer network modeling of integrated biological systems. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

    Science.gov (United States)

    De Domenico, Manlio

    2018-03-01

    Biological systems, from a cell to the human brain, are inherently complex. A powerful representation of such systems, described by an intricate web of relationships across multiple scales, is provided by complex networks. Recently, several studies are highlighting how simple networks - obtained by aggregating or neglecting temporal or categorical description of biological data - are not able to account for the richness of information characterizing biological systems. More complex models, namely multilayer networks, are needed to account for interdependencies, often varying across time, of biological interacting units within a cell, a tissue or parts of an organism.

  3. Biological Networks Entropies: Examples in Neural Memory Networks, Genetic Regulation Networks and Social Epidemic Networks

    Directory of Open Access Journals (Sweden)

    Jacques Demongeot

    2018-01-01

    Full Text Available Networks used in biological applications at different scales (molecule, cell and population are of different types: neuronal, genetic, and social, but they share the same dynamical concepts, in their continuous differential versions (e.g., non-linear Wilson-Cowan system as well as in their discrete Boolean versions (e.g., non-linear Hopfield system; in both cases, the notion of interaction graph G(J associated to its Jacobian matrix J, and also the concepts of frustrated nodes, positive or negative circuits of G(J, kinetic energy, entropy, attractors, structural stability, etc., are relevant and useful for studying the dynamics and the robustness of these systems. We will give some general results available for both continuous and discrete biological networks, and then study some specific applications of three new notions of entropy: (i attractor entropy, (ii isochronal entropy and (iii entropy centrality; in three domains: a neural network involved in the memory evocation, a genetic network responsible of the iron control and a social network accounting for the obesity spread in high school environment.

  4. Networks in biological systems: An investigation of the Gene Ontology as an evolving network

    International Nuclear Information System (INIS)

    Coronnello, C; Tumminello, M; Micciche, S; Mantegna, R.N.

    2009-01-01

    Many biological systems can be described as networks where different elements interact, in order to perform biological processes. We introduce a network associated with the Gene Ontology. Specifically, we construct a correlation-based network where the vertices are the terms of the Gene Ontology and the link between each two terms is weighted on the basis of the number of genes that they have in common. We analyze a filtered network obtained from the correlation-based network and we characterize its evolution over different releases of the Gene Ontology.

  5. Large Pelagics Biological Survey

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Large Pelagics Biological Survey (LPBS) collects additional length and weight information and body parts such as otoliths, caudal vertebrae, dorsal spines, and...

  6. Biological and Environmental Research Network Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Balaji, V. [Princeton Univ., NJ (United States). Earth Science Grid Federation (ESGF); Boden, Tom [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cowley, Dave [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dart, Eli [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). ESNet; Dattoria, Vince [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). ESNet; Desai, Narayan [Argonne National Lab. (ANL), Argonne, IL (United States); Egan, Rob [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Foster, Ian [Argonne National Lab. (ANL), Argonne, IL (United States); Goldstone, Robin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Gregurick, Susan [U.S. Dept. of Energy, Washington, DC (United States). Biological Systems Science Division; Houghton, John [U.S. Dept. of Energy, Washington, DC (United States). Biological and Environmental Research (BER) Program; Izaurralde, Cesar [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Johnston, Bill [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). ESNet; Joseph, Renu [U.S. Dept. of Energy, Washington, DC (United States). Climate and Environmental Sciences Division; Kleese-van Dam, Kerstin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lipton, Mary [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Monga, Inder [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). ESNet; Pritchard, Matt [British Atmospheric Data Centre (BADC), Oxon (United Kingdom); Rotman, Lauren [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). ESNet; Strand, Gary [National Center for Atmospheric Research (NCAR), Boulder, CO (United States); Stuart, Cory [Argonne National Lab. (ANL), Argonne, IL (United States); Tatusova, Tatiana [National Inst. of Health (NIH), Bethesda, MD (United States); Tierney, Brian [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). ESNet; Thomas, Brian [Univ. of California, Berkeley, CA (United States); Williams, Dean N. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zurawski, Jason [Internet2, Washington, DC (United States)

    2013-09-01

    The Energy Sciences Network (ESnet) is the primary provider of network connectivity for the U.S. Department of Energy (DOE) Office of Science (SC), the single largest supporter of basic research in the physical sciences in the United States. In support of SC programs, ESnet regularly updates and refreshes its understanding of the networking requirements of the instruments, facilities, scientists, and science programs that it serves. This focus has helped ESnet be a highly successful enabler of scientific discovery for over 25 years. In November 2012, ESnet and the Office of Biological and Environmental Research (BER) of the DOE SC organized a review to characterize the networking requirements of the programs funded by the BER program office. Several key findings resulted from the review. Among them: 1) The scale of data sets available to science collaborations continues to increase exponentially. This has broad impact, both on the network and on the computational and storage systems connected to the network. 2) Many science collaborations require assistance to cope with the systems and network engineering challenges inherent in managing the rapid growth in data scale. 3) Several science domains operate distributed facilities that rely on high-performance networking for success. Key examples illustrated in this report include the Earth System Grid Federation (ESGF) and the Systems Biology Knowledgebase (KBase). This report expands on these points, and addresses others as well. The report contains a findings section as well as the text of the case studies discussed at the review.

  7. PREFACE: Complex Networks: from Biology to Information Technology

    Science.gov (United States)

    Barrat, A.; Boccaletti, S.; Caldarelli, G.; Chessa, A.; Latora, V.; Motter, A. E.

    2008-06-01

    networks consists of an overview of recent studies on hierarchical networks of phase oscillators. By analysing the evolution of the synchronous dynamics, one can infer details about the underlying network topology. Thus a connection between the dynamical and topological properties of the system is established. The paper Network synchronisation: optimal and pessimal scale-free topologies by Donetti et al explores an optimisation algorithm to study the properties of optimally synchronisable unweighted networks with scale-free degree distribution. It is shown that optimisation leads to a tendency towards disassortativity while networks that are optimally 'un-synchronisable' have a highly assortative string-like structure. The paper Critical line in undirected Kauffman Boolean networks—the role of percolation by Fronczak and Fronczak demonstrates that the percolation underlying the process of damage spreading impacts the position of the critical line in random boolean networks. The critical line results from the fact that the ordered behaviour of small clusters shields the chaotic behaviour of the giant component. In Impact of the updating scheme on stationary states of networks, Radicchi et al explore an interpolation between synchronous and asynchronous updating in a one-dimensional chain of Ising spins to locate a phase transition between phases with an absorbing and a fluctuating stationary state. The properties of attractors in the yeast cell-cycle network are also shown to depend sensitively on the updating mode. As this last contribution shows, a large part of the theoretical activity in the field can be applied to the study of biological systems. The section Biological Applications brings together the following contributions: In Applying weighted network measures to microarray distance matrices, Ahnert et al present a new approach to the analysis of weighted networks, which provides a generalisation to any network measure defined on unweighted networks. The

  8. SBEToolbox: A Matlab Toolbox for Biological Network Analysis.

    Science.gov (United States)

    Konganti, Kranti; Wang, Gang; Yang, Ence; Cai, James J

    2013-01-01

    We present SBEToolbox (Systems Biology and Evolution Toolbox), an open-source Matlab toolbox for biological network analysis. It takes a network file as input, calculates a variety of centralities and topological metrics, clusters nodes into modules, and displays the network using different graph layout algorithms. Straightforward implementation and the inclusion of high-level functions allow the functionality to be easily extended or tailored through developing custom plugins. SBEGUI, a menu-driven graphical user interface (GUI) of SBEToolbox, enables easy access to various network and graph algorithms for programmers and non-programmers alike. All source code and sample data are freely available at https://github.com/biocoder/SBEToolbox/releases.

  9. Content-rich biological network constructed by mining PubMed abstracts

    Directory of Open Access Journals (Sweden)

    Sharp Burt M

    2004-10-01

    Full Text Available Abstract Background The integration of the rapidly expanding corpus of information about the genome, transcriptome, and proteome, engendered by powerful technological advances, such as microarrays, and the availability of genomic sequence from multiple species, challenges the grasp and comprehension of the scientific community. Despite the existence of text-mining methods that identify biological relationships based on the textual co-occurrence of gene/protein terms or similarities in abstract texts, knowledge of the underlying molecular connections on a large scale, which is prerequisite to understanding novel biological processes, lags far behind the accumulation of data. While computationally efficient, the co-occurrence-based approaches fail to characterize (e.g., inhibition or stimulation, directionality biological interactions. Programs with natural language processing (NLP capability have been created to address these limitations, however, they are in general not readily accessible to the public. Results We present a NLP-based text-mining approach, Chilibot, which constructs content-rich relationship networks among biological concepts, genes, proteins, or drugs. Amongst its features, suggestions for new hypotheses can be generated. Lastly, we provide evidence that the connectivity of molecular networks extracted from the biological literature follows the power-law distribution, indicating scale-free topologies consistent with the results of previous experimental analyses. Conclusions Chilibot distills scientific relationships from knowledge available throughout a wide range of biological domains and presents these in a content-rich graphical format, thus integrating general biomedical knowledge with the specialized knowledge and interests of the user. Chilibot http://www.chilibot.net can be accessed free of charge to academic users.

  10. Activating and inhibiting connections in biological network dynamics

    Directory of Open Access Journals (Sweden)

    Knight Rob

    2008-12-01

    Full Text Available Abstract Background Many studies of biochemical networks have analyzed network topology. Such work has suggested that specific types of network wiring may increase network robustness and therefore confer a selective advantage. However, knowledge of network topology does not allow one to predict network dynamical behavior – for example, whether deleting a protein from a signaling network would maintain the network's dynamical behavior, or induce oscillations or chaos. Results Here we report that the balance between activating and inhibiting connections is important in determining whether network dynamics reach steady state or oscillate. We use a simple dynamical model of a network of interacting genes or proteins. Using the model, we study random networks, networks selected for robust dynamics, and examples of biological network topologies. The fraction of activating connections influences whether the network dynamics reach steady state or oscillate. Conclusion The activating fraction may predispose a network to oscillate or reach steady state, and neutral evolution or selection of this parameter may affect the behavior of biological networks. This principle may unify the dynamics of a wide range of cellular networks. Reviewers Reviewed by Sergei Maslov, Eugene Koonin, and Yu (Brandon Xia (nominated by Mark Gerstein. For the full reviews, please go to the Reviewers' comments section.

  11. Emergence of communication in socio-biological networks

    CERN Document Server

    Berea, Anamaria

    2018-01-01

    This book integrates current advances in biology, economics of information and linguistics research through applications using agent-based modeling and social network analysis to develop scenarios of communication and language emergence in the social aspects of biological communications. The book presents a model of communication emergence that can be applied both to human and non-human living organism networks. The model is based on economic concepts and individual behavior fundamental for the study of trust and reputation networks in social science, particularly in economics; it is also based on the theory of the emergence of norms and historical path dependence that has been influential in institutional economics. Also included are mathematical models and code for agent-based models to explore various scenarios of language evolution, as well as a computer application that explores language and communication in biological versus social organisms, and the emergence of various meanings and grammars in human ...

  12. Directed partial correlation: inferring large-scale gene regulatory network through induced topology disruptions.

    Directory of Open Access Journals (Sweden)

    Yinyin Yuan

    Full Text Available Inferring regulatory relationships among many genes based on their temporal variation in transcript abundance has been a popular research topic. Due to the nature of microarray experiments, classical tools for time series analysis lose power since the number of variables far exceeds the number of the samples. In this paper, we describe some of the existing multivariate inference techniques that are applicable to hundreds of variables and show the potential challenges for small-sample, large-scale data. We propose a directed partial correlation (DPC method as an efficient and effective solution to regulatory network inference using these data. Specifically for genomic data, the proposed method is designed to deal with large-scale datasets. It combines the efficiency of partial correlation for setting up network topology by testing conditional independence, and the concept of Granger causality to assess topology change with induced interruptions. The idea is that when a transcription factor is induced artificially within a gene network, the disruption of the network by the induction signifies a genes role in transcriptional regulation. The benchmarking results using GeneNetWeaver, the simulator for the DREAM challenges, provide strong evidence of the outstanding performance of the proposed DPC method. When applied to real biological data, the inferred starch metabolism network in Arabidopsis reveals many biologically meaningful network modules worthy of further investigation. These results collectively suggest DPC is a versatile tool for genomics research. The R package DPC is available for download (http://code.google.com/p/dpcnet/.

  13. Growth Limits in Large Scale Networks

    DEFF Research Database (Denmark)

    Knudsen, Thomas Phillip

    limitations. The rising complexity of network management with the convergence of communications platforms is shown as problematic for both automatic management feasibility and for manpower resource management. In the fourth step the scope is extended to include the present society with the DDN project as its......The Subject of large scale networks is approached from the perspective of the network planner. An analysis of the long term planning problems is presented with the main focus on the changing requirements for large scale networks and the potential problems in meeting these requirements. The problems...... the fundamental technological resources in network technologies are analysed for scalability. Here several technological limits to continued growth are presented. The third step involves a survey of major problems in managing large scale networks given the growth of user requirements and the technological...

  14. Network Biology (http://www.iaees.org/publications/journals/nb/online-version.asp

    Directory of Open Access Journals (Sweden)

    networkbiology@iaees.org

    Full Text Available Network Biology ISSN 2220-8879 URL: http://www.iaees.org/publications/journals/nb/online-version.asp RSS: http://www.iaees.org/publications/journals/nb/rss.xml E-mail: networkbiology@iaees.org Editor-in-Chief: WenJun Zhang Aims and Scope NETWORK BIOLOGY (ISSN 2220-8879; CODEN NBEICS is an open access, peer-reviewed international journal that considers scientific articles in all different areas of network biology. It is the transactions of the International Society of Network Biology. It dedicates to the latest advances in network biology. The goal of this journal is to keep a record of the state-of-the-art research and promote the research work in these fast moving areas. The topics to be covered by Network Biology include, but are not limited to: •Theories, algorithms and programs of network analysis •Innovations and applications of biological networks •Ecological networks, food webs and natural equilibrium •Co-evolution, co-extinction, biodiversity conservation •Metabolic networks, protein-protein interaction networks, biochemical reaction networks, gene networks, transcriptional regulatory networks, cell cycle networks, phylogenetic networks, network motifs •Physiological networksNetwork regulation of metabolic processes, human diseases and ecological systems •Social networks, epidemiological networks •System complexity, self-organized systems, emergence of biological systems, agent-based modeling, individual-based modeling, neural network modeling, and other network-based modeling, etc. We are also interested in short communications that clearly address a specific issue or completely present a new ecological network, food web, or metabolic or gene network, etc. Authors can submit their works to the email box of this journal, networkbiology@iaees.org. All manuscripts submitted to this journal must be previously unpublished and may not be considered for publication elsewhere at any time during review period of this journal

  15. Assessment of network perturbation amplitudes by applying high-throughput data to causal biological networks

    Directory of Open Access Journals (Sweden)

    Martin Florian

    2012-05-01

    Full Text Available Abstract Background High-throughput measurement technologies produce data sets that have the potential to elucidate the biological impact of disease, drug treatment, and environmental agents on humans. The scientific community faces an ongoing challenge in the analysis of these rich data sources to more accurately characterize biological processes that have been perturbed at the mechanistic level. Here, a new approach is built on previous methodologies in which high-throughput data was interpreted using prior biological knowledge of cause and effect relationships. These relationships are structured into network models that describe specific biological processes, such as inflammatory signaling or cell cycle progression. This enables quantitative assessment of network perturbation in response to a given stimulus. Results Four complementary methods were devised to quantify treatment-induced activity changes in processes described by network models. In addition, companion statistics were developed to qualify significance and specificity of the results. This approach is called Network Perturbation Amplitude (NPA scoring because the amplitudes of treatment-induced perturbations are computed for biological network models. The NPA methods were tested on two transcriptomic data sets: normal human bronchial epithelial (NHBE cells treated with the pro-inflammatory signaling mediator TNFα, and HCT116 colon cancer cells treated with the CDK cell cycle inhibitor R547. Each data set was scored against network models representing different aspects of inflammatory signaling and cell cycle progression, and these scores were compared with independent measures of pathway activity in NHBE cells to verify the approach. The NPA scoring method successfully quantified the amplitude of TNFα-induced perturbation for each network model when compared against NF-κB nuclear localization and cell number. In addition, the degree and specificity to which CDK

  16. BFL: a node and edge betweenness based fast layout algorithm for large scale networks

    Science.gov (United States)

    Hashimoto, Tatsunori B; Nagasaki, Masao; Kojima, Kaname; Miyano, Satoru

    2009-01-01

    Background Network visualization would serve as a useful first step for analysis. However, current graph layout algorithms for biological pathways are insensitive to biologically important information, e.g. subcellular localization, biological node and graph attributes, or/and not available for large scale networks, e.g. more than 10000 elements. Results To overcome these problems, we propose the use of a biologically important graph metric, betweenness, a measure of network flow. This metric is highly correlated with many biological phenomena such as lethality and clusters. We devise a new fast parallel algorithm calculating betweenness to minimize the preprocessing cost. Using this metric, we also invent a node and edge betweenness based fast layout algorithm (BFL). BFL places the high-betweenness nodes to optimal positions and allows the low-betweenness nodes to reach suboptimal positions. Furthermore, BFL reduces the runtime by combining a sequential insertion algorim with betweenness. For a graph with n nodes, this approach reduces the expected runtime of the algorithm to O(n2) when considering edge crossings, and to O(n log n) when considering only density and edge lengths. Conclusion Our BFL algorithm is compared against fast graph layout algorithms and approaches requiring intensive optimizations. For gene networks, we show that our algorithm is faster than all layout algorithms tested while providing readability on par with intensive optimization algorithms. We achieve a 1.4 second runtime for a graph with 4000 nodes and 12000 edges on a standard desktop computer. PMID:19146673

  17. Network Analysis Tools: from biological networks to clusters and pathways.

    Science.gov (United States)

    Brohée, Sylvain; Faust, Karoline; Lima-Mendez, Gipsi; Vanderstocken, Gilles; van Helden, Jacques

    2008-01-01

    Network Analysis Tools (NeAT) is a suite of computer tools that integrate various algorithms for the analysis of biological networks: comparison between graphs, between clusters, or between graphs and clusters; network randomization; analysis of degree distribution; network-based clustering and path finding. The tools are interconnected to enable a stepwise analysis of the network through a complete analytical workflow. In this protocol, we present a typical case of utilization, where the tasks above are combined to decipher a protein-protein interaction network retrieved from the STRING database. The results returned by NeAT are typically subnetworks, networks enriched with additional information (i.e., clusters or paths) or tables displaying statistics. Typical networks comprising several thousands of nodes and arcs can be analyzed within a few minutes. The complete protocol can be read and executed in approximately 1 h.

  18. Phylogenetically informed logic relationships improve detection of biological network organization

    Science.gov (United States)

    2011-01-01

    Background A "phylogenetic profile" refers to the presence or absence of a gene across a set of organisms, and it has been proven valuable for understanding gene functional relationships and network organization. Despite this success, few studies have attempted to search beyond just pairwise relationships among genes. Here we search for logic relationships involving three genes, and explore its potential application in gene network analyses. Results Taking advantage of a phylogenetic matrix constructed from the large orthologs database Roundup, we invented a method to create balanced profiles for individual triplets of genes that guarantee equal weight on the different phylogenetic scenarios of coevolution between genes. When we applied this idea to LAPP, the method to search for logic triplets of genes, the balanced profiles resulted in significant performance improvement and the discovery of hundreds of thousands more putative triplets than unadjusted profiles. We found that logic triplets detected biological network organization and identified key proteins and their functions, ranging from neighbouring proteins in local pathways, to well separated proteins in the whole pathway, and to the interactions among different pathways at the system level. Finally, our case study suggested that the directionality in a logic relationship and the profile of a triplet could disclose the connectivity between the triplet and surrounding networks. Conclusion Balanced profiles are superior to the raw profiles employed by traditional methods of phylogenetic profiling in searching for high order gene sets. Gene triplets can provide valuable information in detection of biological network organization and identification of key genes at different levels of cellular interaction. PMID:22172058

  19. Multilevel compression of random walks on networks reveals hierarchical organization in large integrated systems.

    Directory of Open Access Journals (Sweden)

    Martin Rosvall

    Full Text Available To comprehend the hierarchical organization of large integrated systems, we introduce the hierarchical map equation, which reveals multilevel structures in networks. In this information-theoretic approach, we exploit the duality between compression and pattern detection; by compressing a description of a random walker as a proxy for real flow on a network, we find regularities in the network that induce this system-wide flow. Finding the shortest multilevel description of the random walker therefore gives us the best hierarchical clustering of the network--the optimal number of levels and modular partition at each level--with respect to the dynamics on the network. With a novel search algorithm, we extract and illustrate the rich multilevel organization of several large social and biological networks. For example, from the global air traffic network we uncover countries and continents, and from the pattern of scientific communication we reveal more than 100 scientific fields organized in four major disciplines: life sciences, physical sciences, ecology and earth sciences, and social sciences. In general, we find shallow hierarchical structures in globally interconnected systems, such as neural networks, and rich multilevel organizations in systems with highly separated regions, such as road networks.

  20. Novel topological descriptors for analyzing biological networks

    Directory of Open Access Journals (Sweden)

    Varmuza Kurt K

    2010-06-01

    Full Text Available Abstract Background Topological descriptors, other graph measures, and in a broader sense, graph-theoretical methods, have been proven as powerful tools to perform biological network analysis. However, the majority of the developed descriptors and graph-theoretical methods does not have the ability to take vertex- and edge-labels into account, e.g., atom- and bond-types when considering molecular graphs. Indeed, this feature is important to characterize biological networks more meaningfully instead of only considering pure topological information. Results In this paper, we put the emphasis on analyzing a special type of biological networks, namely bio-chemical structures. First, we derive entropic measures to calculate the information content of vertex- and edge-labeled graphs and investigate some useful properties thereof. Second, we apply the mentioned measures combined with other well-known descriptors to supervised machine learning methods for predicting Ames mutagenicity. Moreover, we investigate the influence of our topological descriptors - measures for only unlabeled vs. measures for labeled graphs - on the prediction performance of the underlying graph classification problem. Conclusions Our study demonstrates that the application of entropic measures to molecules representing graphs is useful to characterize such structures meaningfully. For instance, we have found that if one extends the measures for determining the structural information content of unlabeled graphs to labeled graphs, the uniqueness of the resulting indices is higher. Because measures to structurally characterize labeled graphs are clearly underrepresented so far, the further development of such methods might be valuable and fruitful for solving problems within biological network analysis.

  1. Expectation propagation for large scale Bayesian inference of non-linear molecular networks from perturbation data.

    Science.gov (United States)

    Narimani, Zahra; Beigy, Hamid; Ahmad, Ashar; Masoudi-Nejad, Ali; Fröhlich, Holger

    2017-01-01

    Inferring the structure of molecular networks from time series protein or gene expression data provides valuable information about the complex biological processes of the cell. Causal network structure inference has been approached using different methods in the past. Most causal network inference techniques, such as Dynamic Bayesian Networks and ordinary differential equations, are limited by their computational complexity and thus make large scale inference infeasible. This is specifically true if a Bayesian framework is applied in order to deal with the unavoidable uncertainty about the correct model. We devise a novel Bayesian network reverse engineering approach using ordinary differential equations with the ability to include non-linearity. Besides modeling arbitrary, possibly combinatorial and time dependent perturbations with unknown targets, one of our main contributions is the use of Expectation Propagation, an algorithm for approximate Bayesian inference over large scale network structures in short computation time. We further explore the possibility of integrating prior knowledge into network inference. We evaluate the proposed model on DREAM4 and DREAM8 data and find it competitive against several state-of-the-art existing network inference methods.

  2. IR wireless cluster synapses of HYDRA very large neural networks

    Science.gov (United States)

    Jannson, Tomasz; Forrester, Thomas

    2008-04-01

    RF/IR wireless (virtual) synapses are critical components of HYDRA (Hyper-Distributed Robotic Autonomy) neural networks, already discussed in two earlier papers. The HYDRA network has the potential to be very large, up to 10 11-neurons and 10 18-synapses, based on already established technologies (cellular RF telephony and IR-wireless LANs). It is organized into almost fully connected IR-wireless clusters. The HYDRA neurons and synapses are very flexible, simple, and low-cost. They can be modified into a broad variety of biologically-inspired brain-like computing capabilities. In this third paper, we focus on neural hardware in general, and on IR-wireless synapses in particular. Such synapses, based on LED/LD-connections, dominate the HYDRA neural cluster.

  3. OmicsNet: a web-based tool for creation and visual analysis of biological networks in 3D space.

    Science.gov (United States)

    Zhou, Guangyan; Xia, Jianguo

    2018-06-07

    Biological networks play increasingly important roles in omics data integration and systems biology. Over the past decade, many excellent tools have been developed to support creation, analysis and visualization of biological networks. However, important limitations remain: most tools are standalone programs, the majority of them focus on protein-protein interaction (PPI) or metabolic networks, and visualizations often suffer from 'hairball' effects when networks become large. To help address these limitations, we developed OmicsNet - a novel web-based tool that allows users to easily create different types of molecular interaction networks and visually explore them in a three-dimensional (3D) space. Users can upload one or multiple lists of molecules of interest (genes/proteins, microRNAs, transcription factors or metabolites) to create and merge different types of biological networks. The 3D network visualization system was implemented using the powerful Web Graphics Library (WebGL) technology that works natively in most major browsers. OmicsNet supports force-directed layout, multi-layered perspective layout, as well as spherical layout to help visualize and navigate complex networks. A rich set of functions have been implemented to allow users to perform coloring, shading, topology analysis, and enrichment analysis. OmicsNet is freely available at http://www.omicsnet.ca.

  4. Social network size relates to developmental neural sensitivity to biological motion

    Directory of Open Access Journals (Sweden)

    L.A. Kirby

    2018-04-01

    Full Text Available The ability to perceive others’ actions and goals from human motion (i.e., biological motion perception is a critical component of social perception and may be linked to the development of real-world social relationships. Adult research demonstrates two key nodes of the brain’s biological motion perception system—amygdala and posterior superior temporal sulcus (pSTS—are linked to variability in social network properties. The relation between social perception and social network properties, however, has not yet been investigated in middle childhood—a time when individual differences in social experiences and social perception are growing. The aims of this study were to (1 replicate past work showing amygdala and pSTS sensitivity to biological motion in middle childhood; (2 examine age-related changes in the neural sensitivity for biological motion, and (3 determine whether neural sensitivity for biological motion relates to social network characteristics in children. Consistent with past work, we demonstrate a significant relation between social network size and neural sensitivity for biological motion in left pSTS, but do not find age-related change in biological motion perception. This finding offers evidence for the interplay between real-world social experiences and functional brain development and has important implications for understanding disorders of atypical social experience. Keywords: Biological motion, Social networks, Middle childhood, Neural specialization, Brain-behavior relations, pSTS

  5. Discriminative topological features reveal biological network mechanisms

    Directory of Open Access Journals (Sweden)

    Levovitz Chaya

    2004-11-01

    Full Text Available Abstract Background Recent genomic and bioinformatic advances have motivated the development of numerous network models intending to describe graphs of biological, technological, and sociological origin. In most cases the success of a model has been evaluated by how well it reproduces a few key features of the real-world data, such as degree distributions, mean geodesic lengths, and clustering coefficients. Often pairs of models can reproduce these features with indistinguishable fidelity despite being generated by vastly different mechanisms. In such cases, these few target features are insufficient to distinguish which of the different models best describes real world networks of interest; moreover, it is not clear a priori that any of the presently-existing algorithms for network generation offers a predictive description of the networks inspiring them. Results We present a method to assess systematically which of a set of proposed network generation algorithms gives the most accurate description of a given biological network. To derive discriminative classifiers, we construct a mapping from the set of all graphs to a high-dimensional (in principle infinite-dimensional "word space". This map defines an input space for classification schemes which allow us to state unambiguously which models are most descriptive of a given network of interest. Our training sets include networks generated from 17 models either drawn from the literature or introduced in this work. We show that different duplication-mutation schemes best describe the E. coli genetic network, the S. cerevisiae protein interaction network, and the C. elegans neuronal network, out of a set of network models including a linear preferential attachment model and a small-world model. Conclusions Our method is a first step towards systematizing network models and assessing their predictability, and we anticipate its usefulness for a number of communities.

  6. Continuum Modeling of Biological Network Formation

    KAUST Repository

    Albi, Giacomo; Burger, Martin; Haskovec, Jan; Markowich, Peter A.; Schlottbom, Matthias

    2017-01-01

    We present an overview of recent analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transportation networks. The model describes

  7. Network science of biological systems at different scales: A review

    Science.gov (United States)

    Gosak, Marko; Markovič, Rene; Dolenšek, Jurij; Slak Rupnik, Marjan; Marhl, Marko; Stožer, Andraž; Perc, Matjaž

    2018-03-01

    Network science is today established as a backbone for description of structure and function of various physical, chemical, biological, technological, and social systems. Here we review recent advances in the study of complex biological systems that were inspired and enabled by methods of network science. First, we present

  8. Use artificial neural network to align biological ontologies.

    Science.gov (United States)

    Huang, Jingshan; Dang, Jiangbo; Huhns, Michael N; Zheng, W Jim

    2008-09-16

    Being formal, declarative knowledge representation models, ontologies help to address the problem of imprecise terminologies in biological and biomedical research. However, ontologies constructed under the auspices of the Open Biomedical Ontologies (OBO) group have exhibited a great deal of variety, because different parties can design ontologies according to their own conceptual views of the world. It is therefore becoming critical to align ontologies from different parties. During automated/semi-automated alignment across biological ontologies, different semantic aspects, i.e., concept name, concept properties, and concept relationships, contribute in different degrees to alignment results. Therefore, a vector of weights must be assigned to these semantic aspects. It is not trivial to determine what those weights should be, and current methodologies depend a lot on human heuristics. In this paper, we take an artificial neural network approach to learn and adjust these weights, and thereby support a new ontology alignment algorithm, customized for biological ontologies, with the purpose of avoiding some disadvantages in both rule-based and learning-based aligning algorithms. This approach has been evaluated by aligning two real-world biological ontologies, whose features include huge file size, very few instances, concept names in numerical strings, and others. The promising experiment results verify our proposed hypothesis, i.e., three weights for semantic aspects learned from a subset of concepts are representative of all concepts in the same ontology. Therefore, our method represents a large leap forward towards automating biological ontology alignment.

  9. Logic-based models in systems biology: a predictive and parameter-free network analysis method.

    Science.gov (United States)

    Wynn, Michelle L; Consul, Nikita; Merajver, Sofia D; Schnell, Santiago

    2012-11-01

    Highly complex molecular networks, which play fundamental roles in almost all cellular processes, are known to be dysregulated in a number of diseases, most notably in cancer. As a consequence, there is a critical need to develop practical methodologies for constructing and analysing molecular networks at a systems level. Mathematical models built with continuous differential equations are an ideal methodology because they can provide a detailed picture of a network's dynamics. To be predictive, however, differential equation models require that numerous parameters be known a priori and this information is almost never available. An alternative dynamical approach is the use of discrete logic-based models that can provide a good approximation of the qualitative behaviour of a biochemical system without the burden of a large parameter space. Despite their advantages, there remains significant resistance to the use of logic-based models in biology. Here, we address some common concerns and provide a brief tutorial on the use of logic-based models, which we motivate with biological examples.

  10. Statistical assessment of crosstalk enrichment between gene groups in biological networks.

    Science.gov (United States)

    McCormack, Theodore; Frings, Oliver; Alexeyenko, Andrey; Sonnhammer, Erik L L

    2013-01-01

    Analyzing groups of functionally coupled genes or proteins in the context of global interaction networks has become an important aspect of bioinformatic investigations. Assessing the statistical significance of crosstalk enrichment between or within groups of genes can be a valuable tool for functional annotation of experimental gene sets. Here we present CrossTalkZ, a statistical method and software to assess the significance of crosstalk enrichment between pairs of gene or protein groups in large biological networks. We demonstrate that the standard z-score is generally an appropriate and unbiased statistic. We further evaluate the ability of four different methods to reliably recover crosstalk within known biological pathways. We conclude that the methods preserving the second-order topological network properties perform best. Finally, we show how CrossTalkZ can be used to annotate experimental gene sets using known pathway annotations and that its performance at this task is superior to gene enrichment analysis (GEA). CrossTalkZ (available at http://sonnhammer.sbc.su.se/download/software/CrossTalkZ/) is implemented in C++, easy to use, fast, accepts various input file formats, and produces a number of statistics. These include z-score, p-value, false discovery rate, and a test of normality for the null distributions.

  11. The potential of text mining in data integration and network biology for plant research: a case study on Arabidopsis.

    Science.gov (United States)

    Van Landeghem, Sofie; De Bodt, Stefanie; Drebert, Zuzanna J; Inzé, Dirk; Van de Peer, Yves

    2013-03-01

    Despite the availability of various data repositories for plant research, a wealth of information currently remains hidden within the biomolecular literature. Text mining provides the necessary means to retrieve these data through automated processing of texts. However, only recently has advanced text mining methodology been implemented with sufficient computational power to process texts at a large scale. In this study, we assess the potential of large-scale text mining for plant biology research in general and for network biology in particular using a state-of-the-art text mining system applied to all PubMed abstracts and PubMed Central full texts. We present extensive evaluation of the textual data for Arabidopsis thaliana, assessing the overall accuracy of this new resource for usage in plant network analyses. Furthermore, we combine text mining information with both protein-protein and regulatory interactions from experimental databases. Clusters of tightly connected genes are delineated from the resulting network, illustrating how such an integrative approach is essential to grasp the current knowledge available for Arabidopsis and to uncover gene information through guilt by association. All large-scale data sets, as well as the manually curated textual data, are made publicly available, hereby stimulating the application of text mining data in future plant biology studies.

  12. Limits to the development of feed-forward structures in large recurrent neuronal networks

    Directory of Open Access Journals (Sweden)

    Susanne Kunkel

    2011-02-01

    Full Text Available Spike-timing dependent plasticity (STDP has traditionally been of great interest to theoreticians, as it seems to provide an answer to the question of how the brain can develop functional structure in response to repeated stimuli. However, despite this high level of interest, convincing demonstrations of this capacity in large, initially random networks have not been forthcoming. Such demonstrations as there are typically rely on constraining the problem artificially. Techniques include employing additional pruning mechanisms or STDP rules that enhance symmetry breaking, simulating networks with low connectivity that magnify competition between synapses, or combinations of the above. In this paper we first review modeling choices that carry particularly high risks of producing non-generalizable results in the context of STDP in recurrent networks. We then develop a theory for the development of feed-forward structure in random networks and conclude that an unstable fixed point in the dynamics prevents the stable propagation of structure in recurrent networks with weight-dependent STDP. We demonstrate that the key predictions of the theory hold in large-scale simulations. The theory provides insight into the reasons why such development does not take place in unconstrained systems and enables us to identify candidate biologically motivated adaptations to the balanced random network model that might enable it.

  13. From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data.

    Science.gov (United States)

    Vella, Danila; Zoppis, Italo; Mauri, Giancarlo; Mauri, Pierluigi; Di Silvestre, Dario

    2017-12-01

    The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.

  14. A new asynchronous parallel algorithm for inferring large-scale gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Xiangyun Xiao

    Full Text Available The reconstruction of gene regulatory networks (GRNs from high-throughput experimental data has been considered one of the most important issues in systems biology research. With the development of high-throughput technology and the complexity of biological problems, we need to reconstruct GRNs that contain thousands of genes. However, when many existing algorithms are used to handle these large-scale problems, they will encounter two important issues: low accuracy and high computational cost. To overcome these difficulties, the main goal of this study is to design an effective parallel algorithm to infer large-scale GRNs based on high-performance parallel computing environments. In this study, we proposed a novel asynchronous parallel framework to improve the accuracy and lower the time complexity of large-scale GRN inference by combining splitting technology and ordinary differential equation (ODE-based optimization. The presented algorithm uses the sparsity and modularity of GRNs to split whole large-scale GRNs into many small-scale modular subnetworks. Through the ODE-based optimization of all subnetworks in parallel and their asynchronous communications, we can easily obtain the parameters of the whole network. To test the performance of the proposed approach, we used well-known benchmark datasets from Dialogue for Reverse Engineering Assessments and Methods challenge (DREAM, experimentally determined GRN of Escherichia coli and one published dataset that contains more than 10 thousand genes to compare the proposed approach with several popular algorithms on the same high-performance computing environments in terms of both accuracy and time complexity. The numerical results demonstrate that our parallel algorithm exhibits obvious superiority in inferring large-scale GRNs.

  15. A new asynchronous parallel algorithm for inferring large-scale gene regulatory networks.

    Science.gov (United States)

    Xiao, Xiangyun; Zhang, Wei; Zou, Xiufen

    2015-01-01

    The reconstruction of gene regulatory networks (GRNs) from high-throughput experimental data has been considered one of the most important issues in systems biology research. With the development of high-throughput technology and the complexity of biological problems, we need to reconstruct GRNs that contain thousands of genes. However, when many existing algorithms are used to handle these large-scale problems, they will encounter two important issues: low accuracy and high computational cost. To overcome these difficulties, the main goal of this study is to design an effective parallel algorithm to infer large-scale GRNs based on high-performance parallel computing environments. In this study, we proposed a novel asynchronous parallel framework to improve the accuracy and lower the time complexity of large-scale GRN inference by combining splitting technology and ordinary differential equation (ODE)-based optimization. The presented algorithm uses the sparsity and modularity of GRNs to split whole large-scale GRNs into many small-scale modular subnetworks. Through the ODE-based optimization of all subnetworks in parallel and their asynchronous communications, we can easily obtain the parameters of the whole network. To test the performance of the proposed approach, we used well-known benchmark datasets from Dialogue for Reverse Engineering Assessments and Methods challenge (DREAM), experimentally determined GRN of Escherichia coli and one published dataset that contains more than 10 thousand genes to compare the proposed approach with several popular algorithms on the same high-performance computing environments in terms of both accuracy and time complexity. The numerical results demonstrate that our parallel algorithm exhibits obvious superiority in inferring large-scale GRNs.

  16. Using biological networks to improve our understanding of infectious diseases

    Directory of Open Access Journals (Sweden)

    Nicola J. Mulder

    2014-08-01

    Full Text Available Infectious diseases are the leading cause of death, particularly in developing countries. Although many drugs are available for treating the most common infectious diseases, in many cases the mechanism of action of these drugs or even their targets in the pathogen remain unknown. In addition, the key factors or processes in pathogens that facilitate infection and disease progression are often not well understood. Since proteins do not work in isolation, understanding biological systems requires a better understanding of the interconnectivity between proteins in different pathways and processes, which includes both physical and other functional interactions. Such biological networks can be generated within organisms or between organisms sharing a common environment using experimental data and computational predictions. Though different data sources provide different levels of accuracy, confidence in interactions can be measured using interaction scores. Connections between interacting proteins in biological networks can be represented as graphs and edges, and thus studied using existing algorithms and tools from graph theory. There are many different applications of biological networks, and here we discuss three such applications, specifically applied to the infectious disease tuberculosis, with its causative agent Mycobacterium tuberculosis and host, Homo sapiens. The applications include the use of the networks for function prediction, comparison of networks for evolutionary studies, and the generation and use of host–pathogen interaction networks.

  17. Community Detection for Large Graphs

    KAUST Repository

    Peng, Chengbin; Kolda, Tamara G.; Pinar, Ali; Zhang, Zhihua; Keyes, David E.

    2014-01-01

    Many real world networks have inherent community structures, including social networks, transportation networks, biological networks, etc. For large scale networks with millions or billions of nodes in real-world applications, accelerating current

  18. Revisiting the variation of clustering coefficient of biological networks suggests new modular structure.

    Science.gov (United States)

    Hao, Dapeng; Ren, Cong; Li, Chuanxing

    2012-05-01

    A central idea in biology is the hierarchical organization of cellular processes. A commonly used method to identify the hierarchical modular organization of network relies on detecting a global signature known as variation of clustering coefficient (so-called modularity scaling). Although several studies have suggested other possible origins of this signature, it is still widely used nowadays to identify hierarchical modularity, especially in the analysis of biological networks. Therefore, a further and systematical investigation of this signature for different types of biological networks is necessary. We analyzed a variety of biological networks and found that the commonly used signature of hierarchical modularity is actually the reflection of spoke-like topology, suggesting a different view of network architecture. We proved that the existence of super-hubs is the origin that the clustering coefficient of a node follows a particular scaling law with degree k in metabolic networks. To study the modularity of biological networks, we systematically investigated the relationship between repulsion of hubs and variation of clustering coefficient. We provided direct evidences for repulsion between hubs being the underlying origin of the variation of clustering coefficient, and found that for biological networks having no anti-correlation between hubs, such as gene co-expression network, the clustering coefficient doesn't show dependence of degree. Here we have shown that the variation of clustering coefficient is neither sufficient nor exclusive for a network to be hierarchical. Our results suggest the existence of spoke-like modules as opposed to "deterministic model" of hierarchical modularity, and suggest the need to reconsider the organizational principle of biological hierarchy.

  19. PKI security in large-scale healthcare networks.

    Science.gov (United States)

    Mantas, Georgios; Lymberopoulos, Dimitrios; Komninos, Nikos

    2012-06-01

    During the past few years a lot of PKI (Public Key Infrastructures) infrastructures have been proposed for healthcare networks in order to ensure secure communication services and exchange of data among healthcare professionals. However, there is a plethora of challenges in these healthcare PKI infrastructures. Especially, there are a lot of challenges for PKI infrastructures deployed over large-scale healthcare networks. In this paper, we propose a PKI infrastructure to ensure security in a large-scale Internet-based healthcare network connecting a wide spectrum of healthcare units geographically distributed within a wide region. Furthermore, the proposed PKI infrastructure facilitates the trust issues that arise in a large-scale healthcare network including multi-domain PKI infrastructures.

  20. Automatic Generation of Connectivity for Large-Scale Neuronal Network Models through Structural Plasticity.

    Science.gov (United States)

    Diaz-Pier, Sandra; Naveau, Mikaël; Butz-Ostendorf, Markus; Morrison, Abigail

    2016-01-01

    With the emergence of new high performance computation technology in the last decade, the simulation of large scale neural networks which are able to reproduce the behavior and structure of the brain has finally become an achievable target of neuroscience. Due to the number of synaptic connections between neurons and the complexity of biological networks, most contemporary models have manually defined or static connectivity. However, it is expected that modeling the dynamic generation and deletion of the links among neurons, locally and between different regions of the brain, is crucial to unravel important mechanisms associated with learning, memory and healing. Moreover, for many neural circuits that could potentially be modeled, activity data is more readily and reliably available than connectivity data. Thus, a framework that enables networks to wire themselves on the basis of specified activity targets can be of great value in specifying network models where connectivity data is incomplete or has large error margins. To address these issues, in the present work we present an implementation of a model of structural plasticity in the neural network simulator NEST. In this model, synapses consist of two parts, a pre- and a post-synaptic element. Synapses are created and deleted during the execution of the simulation following local homeostatic rules until a mean level of electrical activity is reached in the network. We assess the scalability of the implementation in order to evaluate its potential usage in the self generation of connectivity of large scale networks. We show and discuss the results of simulations on simple two population networks and more complex models of the cortical microcircuit involving 8 populations and 4 layers using the new framework.

  1. Color encoding in biologically-inspired convolutional neural networks.

    Science.gov (United States)

    Rafegas, Ivet; Vanrell, Maria

    2018-05-11

    Convolutional Neural Networks have been proposed as suitable frameworks to model biological vision. Some of these artificial networks showed representational properties that rival primate performances in object recognition. In this paper we explore how color is encoded in a trained artificial network. It is performed by estimating a color selectivity index for each neuron, which allows us to describe the neuron activity to a color input stimuli. The index allows us to classify whether they are color selective or not and if they are of a single or double color. We have determined that all five convolutional layers of the network have a large number of color selective neurons. Color opponency clearly emerges in the first layer, presenting 4 main axes (Black-White, Red-Cyan, Blue-Yellow and Magenta-Green), but this is reduced and rotated as we go deeper into the network. In layer 2 we find a denser hue sampling of color neurons and opponency is reduced almost to one new main axis, the Bluish-Orangish coinciding with the dataset bias. In layers 3, 4 and 5 color neurons are similar amongst themselves, presenting different type of neurons that detect specific colored objects (e.g., orangish faces), specific surrounds (e.g., blue sky) or specific colored or contrasted object-surround configurations (e.g. blue blob in a green surround). Overall, our work concludes that color and shape representation are successively entangled through all the layers of the studied network, revealing certain parallelisms with the reported evidences in primate brains that can provide useful insight into intermediate hierarchical spatio-chromatic representations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Social traits, social networks and evolutionary biology.

    Science.gov (United States)

    Fisher, D N; McAdam, A G

    2017-12-01

    effects) provides the potential to understand how entire networks of social interactions in populations influence phenotypes and predict how these traits may evolve. By theoretical integration of social network analysis and quantitative genetics, we hope to identify areas of compatibility and incompatibility and to direct research efforts towards the most promising areas. Continuing this synthesis could provide important insights into the evolution of traits expressed in a social context and the evolutionary consequences of complex and nuanced social phenotypes. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  3. Spatiotemporal network motif reveals the biological traits of developmental gene regulatory networks in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Kim Man-Sun

    2012-05-01

    Full Text Available Abstract Background Network motifs provided a “conceptual tool” for understanding the functional principles of biological networks, but such motifs have primarily been used to consider static network structures. Static networks, however, cannot be used to reveal time- and region-specific traits of biological systems. To overcome this limitation, we proposed the concept of a “spatiotemporal network motif,” a spatiotemporal sequence of network motifs of sub-networks which are active only at specific time points and body parts. Results On the basis of this concept, we analyzed the developmental gene regulatory network of the Drosophila melanogaster embryo. We identified spatiotemporal network motifs and investigated their distribution pattern in time and space. As a result, we found how key developmental processes are temporally and spatially regulated by the gene network. In particular, we found that nested feedback loops appeared frequently throughout the entire developmental process. From mathematical simulations, we found that mutual inhibition in the nested feedback loops contributes to the formation of spatial expression patterns. Conclusions Taken together, the proposed concept and the simulations can be used to unravel the design principle of developmental gene regulatory networks.

  4. APPLICATION OF UKRAINIAN GRID INFRASTRUCTURE FOR INVESTIGATION OF NONLINEAR DYNAMICS IN LARGE NEURONAL NETWORKS

    Directory of Open Access Journals (Sweden)

    O. О. Sudakov

    2015-12-01

    Full Text Available In present work the Ukrainian National Grid (UNG infrastructure was applied for investigation of synchronization in large networks of interacting neurons. This application is important for solving of modern neuroscience problems related to mechanisms of nervous system activities (memory, cognition etc. and nervous pathologies (epilepsy, Parkinsonism, etc.. Modern non-linear dynamics theories and applications provides powerful basis for computer simulations of biological neuronal networks and investigation of phenomena which mechanisms hardly could be clarified by other approaches. Cubic millimeter of brain tissue contains about 105 neurons, so realistic (Hodgkin-Huxley model and phenomenological (Kuramoto-Sakaguchi, FitzHugh-Nagumo, etc. models simulations require consideration of large neurons numbers.

  5. Revisiting the variation of clustering coefficient of biological networks suggests new modular structure

    Directory of Open Access Journals (Sweden)

    Hao Dapeng

    2012-05-01

    Full Text Available Abstract Background A central idea in biology is the hierarchical organization of cellular processes. A commonly used method to identify the hierarchical modular organization of network relies on detecting a global signature known as variation of clustering coefficient (so-called modularity scaling. Although several studies have suggested other possible origins of this signature, it is still widely used nowadays to identify hierarchical modularity, especially in the analysis of biological networks. Therefore, a further and systematical investigation of this signature for different types of biological networks is necessary. Results We analyzed a variety of biological networks and found that the commonly used signature of hierarchical modularity is actually the reflection of spoke-like topology, suggesting a different view of network architecture. We proved that the existence of super-hubs is the origin that the clustering coefficient of a node follows a particular scaling law with degree k in metabolic networks. To study the modularity of biological networks, we systematically investigated the relationship between repulsion of hubs and variation of clustering coefficient. We provided direct evidences for repulsion between hubs being the underlying origin of the variation of clustering coefficient, and found that for biological networks having no anti-correlation between hubs, such as gene co-expression network, the clustering coefficient doesn’t show dependence of degree. Conclusions Here we have shown that the variation of clustering coefficient is neither sufficient nor exclusive for a network to be hierarchical. Our results suggest the existence of spoke-like modules as opposed to “deterministic model” of hierarchical modularity, and suggest the need to reconsider the organizational principle of biological hierarchy.

  6. Visual analysis of transcriptome data in the context of anatomical structures and biological networks

    Directory of Open Access Journals (Sweden)

    Astrid eJunker

    2012-11-01

    Full Text Available The complexity and temporal as well as spatial resolution of transcriptome datasets is constantly increasing due to extensive technological developments. Here we present methods for advanced visualization and intuitive exploration of transcriptomics data as necessary prerequisites in order to facilitate the gain of biological knowledge. Color-coding of structural images based on the expression level enables a fast visual data analysis in the background of the examined biological system. The network-based exploration of these visualizations allows for comparative analysis of genes with specific transcript patterns and supports the extraction of functional relationships even from large datasets. In order to illustrate the presented methods, the tool HIVE was applied for visualization and exploration of database-retrieved expression data for master regulators of Arabidopsis thaliana flower and seed development in the context of corresponding tissue-specific regulatory networks.

  7. Epigenetics and Why Biological Networks are More Controllable than Expected

    Science.gov (United States)

    Motter, Adilson

    2013-03-01

    A fundamental property of networks is that perturbations to one node can affect other nodes, potentially causing the entire system to change behavior or fail. In this talk, I will show that it is possible to exploit this same principle to control network behavior. This approach takes advantage of the nonlinear dynamics inherent to real networks, and allows bringing the system to a desired target state even when this state is not directly accessible or the linear counterpart is not controllable. Applications show that this framework permits both reprogramming a network to a desired task as well as rescuing networks from the brink of failure, which I will illustrate through various biological problems. I will also briefly review the progress our group has made over the past 5 years on related control of complex networks in non-biological domains.

  8. Analysis and logical modeling of biological signaling transduction networks

    Science.gov (United States)

    Sun, Zhongyao

    The study of network theory and its application span across a multitude of seemingly disparate fields of science and technology: computer science, biology, social science, linguistics, etc. It is the intrinsic similarities embedded in the entities and the way they interact with one another in these systems that link them together. In this dissertation, I present from both the aspect of theoretical analysis and the aspect of application three projects, which primarily focus on signal transduction networks in biology. In these projects, I assembled a network model through extensively perusing literature, performed model-based simulations and validation, analyzed network topology, and proposed a novel network measure. The application of network modeling to the system of stomatal opening in plants revealed a fundamental question about the process that has been left unanswered in decades. The novel measure of the redundancy of signal transduction networks with Boolean dynamics by calculating its maximum node-independent elementary signaling mode set accurately predicts the effect of single node knockout in such signaling processes. The three projects as an organic whole advance the understanding of a real system as well as the behavior of such network models, giving me an opportunity to take a glimpse at the dazzling facets of the immense world of network science.

  9. Identifying influential nodes in large-scale directed networks: the role of clustering.

    Science.gov (United States)

    Chen, Duan-Bing; Gao, Hui; Lü, Linyuan; Zhou, Tao

    2013-01-01

    Identifying influential nodes in very large-scale directed networks is a big challenge relevant to disparate applications, such as accelerating information propagation, controlling rumors and diseases, designing search engines, and understanding hierarchical organization of social and biological networks. Known methods range from node centralities, such as degree, closeness and betweenness, to diffusion-based processes, like PageRank and LeaderRank. Some of these methods already take into account the influences of a node's neighbors but do not directly make use of the interactions among it's neighbors. Local clustering is known to have negative impacts on the information spreading. We further show empirically that it also plays a negative role in generating local connections. Inspired by these facts, we propose a local ranking algorithm named ClusterRank, which takes into account not only the number of neighbors and the neighbors' influences, but also the clustering coefficient. Subject to the susceptible-infected-recovered (SIR) spreading model with constant infectivity, experimental results on two directed networks, a social network extracted from delicious.com and a large-scale short-message communication network, demonstrate that the ClusterRank outperforms some benchmark algorithms such as PageRank and LeaderRank. Furthermore, ClusterRank can also be applied to undirected networks where the superiority of ClusterRank is significant compared with degree centrality and k-core decomposition. In addition, ClusterRank, only making use of local information, is much more efficient than global methods: It takes only 191 seconds for a network with about [Formula: see text] nodes, more than 15 times faster than PageRank.

  10. Identifying influential nodes in large-scale directed networks: the role of clustering.

    Directory of Open Access Journals (Sweden)

    Duan-Bing Chen

    Full Text Available Identifying influential nodes in very large-scale directed networks is a big challenge relevant to disparate applications, such as accelerating information propagation, controlling rumors and diseases, designing search engines, and understanding hierarchical organization of social and biological networks. Known methods range from node centralities, such as degree, closeness and betweenness, to diffusion-based processes, like PageRank and LeaderRank. Some of these methods already take into account the influences of a node's neighbors but do not directly make use of the interactions among it's neighbors. Local clustering is known to have negative impacts on the information spreading. We further show empirically that it also plays a negative role in generating local connections. Inspired by these facts, we propose a local ranking algorithm named ClusterRank, which takes into account not only the number of neighbors and the neighbors' influences, but also the clustering coefficient. Subject to the susceptible-infected-recovered (SIR spreading model with constant infectivity, experimental results on two directed networks, a social network extracted from delicious.com and a large-scale short-message communication network, demonstrate that the ClusterRank outperforms some benchmark algorithms such as PageRank and LeaderRank. Furthermore, ClusterRank can also be applied to undirected networks where the superiority of ClusterRank is significant compared with degree centrality and k-core decomposition. In addition, ClusterRank, only making use of local information, is much more efficient than global methods: It takes only 191 seconds for a network with about [Formula: see text] nodes, more than 15 times faster than PageRank.

  11. Identifying Influential Nodes in Large-Scale Directed Networks: The Role of Clustering

    Science.gov (United States)

    Chen, Duan-Bing; Gao, Hui; Lü, Linyuan; Zhou, Tao

    2013-01-01

    Identifying influential nodes in very large-scale directed networks is a big challenge relevant to disparate applications, such as accelerating information propagation, controlling rumors and diseases, designing search engines, and understanding hierarchical organization of social and biological networks. Known methods range from node centralities, such as degree, closeness and betweenness, to diffusion-based processes, like PageRank and LeaderRank. Some of these methods already take into account the influences of a node’s neighbors but do not directly make use of the interactions among it’s neighbors. Local clustering is known to have negative impacts on the information spreading. We further show empirically that it also plays a negative role in generating local connections. Inspired by these facts, we propose a local ranking algorithm named ClusterRank, which takes into account not only the number of neighbors and the neighbors’ influences, but also the clustering coefficient. Subject to the susceptible-infected-recovered (SIR) spreading model with constant infectivity, experimental results on two directed networks, a social network extracted from delicious.com and a large-scale short-message communication network, demonstrate that the ClusterRank outperforms some benchmark algorithms such as PageRank and LeaderRank. Furthermore, ClusterRank can also be applied to undirected networks where the superiority of ClusterRank is significant compared with degree centrality and k-core decomposition. In addition, ClusterRank, only making use of local information, is much more efficient than global methods: It takes only 191 seconds for a network with about nodes, more than 15 times faster than PageRank. PMID:24204833

  12. Two classes of bipartite networks: nested biological and social systems.

    Science.gov (United States)

    Burgos, Enrique; Ceva, Horacio; Hernández, Laura; Perazzo, R P J; Devoto, Mariano; Medan, Diego

    2008-10-01

    Bipartite graphs have received some attention in the study of social networks and of biological mutualistic systems. A generalization of a previous model is presented, that evolves the topology of the graph in order to optimally account for a given contact preference rule between the two guilds of the network. As a result, social and biological graphs are classified as belonging to two clearly different classes. Projected graphs, linking the agents of only one guild, are obtained from the original bipartite graph. The corresponding evolution of its statistical properties is also studied. An example of a biological mutualistic network is analyzed in detail, and it is found that the model provides a very good fitting of all the main statistical features. The model also provides a proper qualitative description of the same features observed in social webs, suggesting the possible reasons underlying the difference in the organization of these two kinds of bipartite networks.

  13. Bayesian Network Webserver: a comprehensive tool for biological network modeling.

    Science.gov (United States)

    Ziebarth, Jesse D; Bhattacharya, Anindya; Cui, Yan

    2013-11-01

    The Bayesian Network Webserver (BNW) is a platform for comprehensive network modeling of systems genetics and other biological datasets. It allows users to quickly and seamlessly upload a dataset, learn the structure of the network model that best explains the data and use the model to understand relationships between network variables. Many datasets, including those used to create genetic network models, contain both discrete (e.g. genotype) and continuous (e.g. gene expression traits) variables, and BNW allows for modeling hybrid datasets. Users of BNW can incorporate prior knowledge during structure learning through an easy-to-use structural constraint interface. After structure learning, users are immediately presented with an interactive network model, which can be used to make testable hypotheses about network relationships. BNW, including a downloadable structure learning package, is available at http://compbio.uthsc.edu/BNW. (The BNW interface for adding structural constraints uses HTML5 features that are not supported by current version of Internet Explorer. We suggest using other browsers (e.g. Google Chrome or Mozilla Firefox) when accessing BNW). ycui2@uthsc.edu. Supplementary data are available at Bioinformatics online.

  14. Fast grid layout algorithm for biological networks with sweep calculation.

    Science.gov (United States)

    Kojima, Kaname; Nagasaki, Masao; Miyano, Satoru

    2008-06-15

    Properly drawn biological networks are of great help in the comprehension of their characteristics. The quality of the layouts for retrieved biological networks is critical for pathway databases. However, since it is unrealistic to manually draw biological networks for every retrieval, automatic drawing algorithms are essential. Grid layout algorithms handle various biological properties such as aligning vertices having the same attributes and complicated positional constraints according to their subcellular localizations; thus, they succeed in providing biologically comprehensible layouts. However, existing grid layout algorithms are not suitable for real-time drawing, which is one of requisites for applications to pathway databases, due to their high-computational cost. In addition, they do not consider edge directions and their resulting layouts lack traceability for biochemical reactions and gene regulations, which are the most important features in biological networks. We devise a new calculation method termed sweep calculation and reduce the time complexity of the current grid layout algorithms through its encoding and decoding processes. We conduct practical experiments by using 95 pathway models of various sizes from TRANSPATH and show that our new grid layout algorithm is much faster than existing grid layout algorithms. For the cost function, we introduce a new component that penalizes undesirable edge directions to avoid the lack of traceability in pathways due to the differences in direction between in-edges and out-edges of each vertex. Java implementations of our layout algorithms are available in Cell Illustrator. masao@ims.u-tokyo.ac.jp Supplementary data are available at Bioinformatics online.

  15. GraphAlignment: Bayesian pairwise alignment of biological networks

    Czech Academy of Sciences Publication Activity Database

    Kolář, Michal; Meier, J.; Mustonen, V.; Lässig, M.; Berg, J.

    2012-01-01

    Roč. 6, November 21 (2012) ISSN 1752-0509 Grant - others:Deutsche Forschungsgemeinschaft(DE) SFB 680; Deutsche Forschungsgemeinschaft(DE) SFB-TR12; Deutsche Forschungsgemeinschaft(DE) BE 2478/2-1 Institutional research plan: CEZ:AV0Z50520514 Keywords : Graph alignment * Biological networks * Parameter estimation * Bioconductor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.982, year: 2012

  16. The Potential of Text Mining in Data Integration and Network Biology for Plant Research: A Case Study on Arabidopsis[C][W

    Science.gov (United States)

    Van Landeghem, Sofie; De Bodt, Stefanie; Drebert, Zuzanna J.; Inzé, Dirk; Van de Peer, Yves

    2013-01-01

    Despite the availability of various data repositories for plant research, a wealth of information currently remains hidden within the biomolecular literature. Text mining provides the necessary means to retrieve these data through automated processing of texts. However, only recently has advanced text mining methodology been implemented with sufficient computational power to process texts at a large scale. In this study, we assess the potential of large-scale text mining for plant biology research in general and for network biology in particular using a state-of-the-art text mining system applied to all PubMed abstracts and PubMed Central full texts. We present extensive evaluation of the textual data for Arabidopsis thaliana, assessing the overall accuracy of this new resource for usage in plant network analyses. Furthermore, we combine text mining information with both protein–protein and regulatory interactions from experimental databases. Clusters of tightly connected genes are delineated from the resulting network, illustrating how such an integrative approach is essential to grasp the current knowledge available for Arabidopsis and to uncover gene information through guilt by association. All large-scale data sets, as well as the manually curated textual data, are made publicly available, hereby stimulating the application of text mining data in future plant biology studies. PMID:23532071

  17. Visual data mining of biological networks: one size does not fit all.

    Directory of Open Access Journals (Sweden)

    Chiara Pastrello

    Full Text Available High-throughput technologies produce massive amounts of data. However, individual methods yield data specific to the technique used and biological setup. The integration of such diverse data is necessary for the qualitative analysis of information relevant to hypotheses or discoveries. It is often useful to integrate these datasets using pathways and protein interaction networks to get a broader view of the experiment. The resulting network needs to be able to focus on either the large-scale picture or on the more detailed small-scale subsets, depending on the research question and goals. In this tutorial, we illustrate a workflow useful to integrate, analyze, and visualize data from different sources, and highlight important features of tools to support such analyses.

  18. CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks.

    Science.gov (United States)

    Li, Min; Li, Dongyan; Tang, Yu; Wu, Fangxiang; Wang, Jianxin

    2017-08-31

    Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster.

  19. Learning Local Components to Understand Large Bayesian Networks

    DEFF Research Database (Denmark)

    Zeng, Yifeng; Xiang, Yanping; Cordero, Jorge

    2009-01-01

    (domain experts) to extract accurate information from a large Bayesian network due to dimensional difficulty. We define a formulation of local components and propose a clustering algorithm to learn such local components given complete data. The algorithm groups together most inter-relevant attributes......Bayesian networks are known for providing an intuitive and compact representation of probabilistic information and allowing the creation of models over a large and complex domain. Bayesian learning and reasoning are nontrivial for a large Bayesian network. In parallel, it is a tough job for users...... in a domain. We evaluate its performance on three benchmark Bayesian networks and provide results in support. We further show that the learned components may represent local knowledge more precisely in comparison to the full Bayesian networks when working with a small amount of data....

  20. Local and global control of ecological and biological networks

    OpenAIRE

    Alessandro Ferrarini

    2014-01-01

    Recently, I introduced a methodological framework so that ecological and biological networks can be controlled both from inside and outside by coupling network dynamics and evolutionary modelling. The endogenous control requires the network to be optimized at the beginning of its dynamics (by acting upon nodes, edges or both) so that it will then go inertially to the desired state. Instead, the exogenous control requires that exogenous controllers act upon the network at each time step. By th...

  1. Quantifying the connectivity of scale-free and biological networks

    Energy Technology Data Exchange (ETDEWEB)

    Shiner, J.S. E-mail: shiner@alumni.duke.edu; Davison, Matt E-mail: mdavison@uwo.ca

    2004-07-01

    Scale-free and biological networks follow a power law distribution p{sub k}{proportional_to}k{sup -{alpha}} for the probability that a node is connected to k other nodes; the corresponding ranges for {alpha} (biological: 1<{alpha}<2; scale-free: 2<{alpha}{<=}3) yield a diverging variance for the connectivity k and lack of predictability for the average connectivity. Predictability can be achieved with the Renyi, Tsallis and Landsberg-Vedral extended entropies and corresponding 'disorders' for correctly chosen values of the entropy index q. Escort distributions p{sub k}{proportional_to}k{sup -{alpha}}{sup q} with q>3/{alpha} also yield a nondiverging variance and predictability. It is argued that the Tsallis entropies may be the appropriate quantities for the study of scale-free and biological networks.

  2. Towards a comprehensive understanding of emerging dynamics and function of pancreatic islets: A complex network approach. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

    Science.gov (United States)

    Loppini, Alessandro

    2018-03-01

    Complex network theory represents a comprehensive mathematical framework to investigate biological systems, ranging from sub-cellular and cellular scales up to large-scale networks describing species interactions and ecological systems. In their exhaustive and comprehensive work [1], Gosak et al. discuss several scenarios in which the network approach was able to uncover general properties and underlying mechanisms of cells organization and regulation, tissue functions and cell/tissue failure in pathology, by the study of chemical reaction networks, structural networks and functional connectivities.

  3. Methods of Model Reduction for Large-Scale Biological Systems: A Survey of Current Methods and Trends.

    Science.gov (United States)

    Snowden, Thomas J; van der Graaf, Piet H; Tindall, Marcus J

    2017-07-01

    Complex models of biochemical reaction systems have become increasingly common in the systems biology literature. The complexity of such models can present a number of obstacles for their practical use, often making problems difficult to intuit or computationally intractable. Methods of model reduction can be employed to alleviate the issue of complexity by seeking to eliminate those portions of a reaction network that have little or no effect upon the outcomes of interest, hence yielding simplified systems that retain an accurate predictive capacity. This review paper seeks to provide a brief overview of a range of such methods and their application in the context of biochemical reaction network models. To achieve this, we provide a brief mathematical account of the main methods including timescale exploitation approaches, reduction via sensitivity analysis, optimisation methods, lumping, and singular value decomposition-based approaches. Methods are reviewed in the context of large-scale systems biology type models, and future areas of research are briefly discussed.

  4. Network biology concepts in complex disease comorbidities

    DEFF Research Database (Denmark)

    Hu, Jessica Xin; Thomas, Cecilia Engel; Brunak, Søren

    2016-01-01

    collected electronically, disease co-occurrences are starting to be quantitatively characterized. Linking network dynamics to the real-life, non-ideal patient in whom diseases co-occur and interact provides a valuable basis for generating hypotheses on molecular disease mechanisms, and provides knowledge......The co-occurrence of diseases can inform the underlying network biology of shared and multifunctional genes and pathways. In addition, comorbidities help to elucidate the effects of external exposures, such as diet, lifestyle and patient care. With worldwide health transaction data now often being...

  5. CellNetVis: a web tool for visualization of biological networks using force-directed layout constrained by cellular components.

    Science.gov (United States)

    Heberle, Henry; Carazzolle, Marcelo Falsarella; Telles, Guilherme P; Meirelles, Gabriela Vaz; Minghim, Rosane

    2017-09-13

    The advent of "omics" science has brought new perspectives in contemporary biology through the high-throughput analyses of molecular interactions, providing new clues in protein/gene function and in the organization of biological pathways. Biomolecular interaction networks, or graphs, are simple abstract representations where the components of a cell (e.g. proteins, metabolites etc.) are represented by nodes and their interactions are represented by edges. An appropriate visualization of data is crucial for understanding such networks, since pathways are related to functions that occur in specific regions of the cell. The force-directed layout is an important and widely used technique to draw networks according to their topologies. Placing the networks into cellular compartments helps to quickly identify where network elements are located and, more specifically, concentrated. Currently, only a few tools provide the capability of visually organizing networks by cellular compartments. Most of them cannot handle large and dense networks. Even for small networks with hundreds of nodes the available tools are not able to reposition the network while the user is interacting, limiting the visual exploration capability. Here we propose CellNetVis, a web tool to easily display biological networks in a cell diagram employing a constrained force-directed layout algorithm. The tool is freely available and open-source. It was originally designed for networks generated by the Integrated Interactome System and can be used with networks from others databases, like InnateDB. CellNetVis has demonstrated to be applicable for dynamic investigation of complex networks over a consistent representation of a cell on the Web, with capabilities not matched elsewhere.

  6. Practical characterization of large networks using neighborhood information

    KAUST Repository

    Wang, Pinghui

    2018-02-14

    Characterizing large complex networks such as online social networks through node querying is a challenging task. Network service providers often impose severe constraints on the query rate, hence limiting the sample size to a small fraction of the total network of interest. Various ad hoc subgraph sampling methods have been proposed, but many of them give biased estimates and no theoretical basis on the accuracy. In this work, we focus on developing sampling methods for large networks where querying a node also reveals partial structural information about its neighbors. Our methods are optimized for NoSQL graph databases (if the database can be accessed directly), or utilize Web APIs available on most major large networks for graph sampling. We show that our sampling method has provable convergence guarantees on being an unbiased estimator, and it is more accurate than state-of-the-art methods. We also explore methods to uncover shortest paths between a subset of nodes and detect high degree nodes by sampling only a small fraction of the network of interest. Our results demonstrate that utilizing neighborhood information yields methods that are two orders of magnitude faster than state-of-the-art methods.

  7. QUAL-NET, a high temporal-resolution eutrophication model for large hydrographic networks

    Science.gov (United States)

    Minaudo, Camille; Curie, Florence; Jullian, Yann; Gassama, Nathalie; Moatar, Florentina

    2018-04-01

    To allow climate change impact assessment of water quality in river systems, the scientific community lacks efficient deterministic models able to simulate hydrological and biogeochemical processes in drainage networks at the regional scale, with high temporal resolution and water temperature explicitly determined. The model QUALity-NETwork (QUAL-NET) was developed and tested on the Middle Loire River Corridor, a sub-catchment of the Loire River in France, prone to eutrophication. Hourly variations computed efficiently by the model helped disentangle the complex interactions existing between hydrological and biological processes across different timescales. Phosphorus (P) availability was the most constraining factor for phytoplankton development in the Loire River, but simulating bacterial dynamics in QUAL-NET surprisingly evidenced large amounts of organic matter recycled within the water column through the microbial loop, which delivered significant fluxes of available P and enhanced phytoplankton growth. This explained why severe blooms still occur in the Loire River despite large P input reductions since 1990. QUAL-NET could be used to study past evolutions or predict future trajectories under climate change and land use scenarios.

  8. QUAL-NET, a high temporal-resolution eutrophication model for large hydrographic networks

    Directory of Open Access Journals (Sweden)

    C. Minaudo

    2018-04-01

    Full Text Available To allow climate change impact assessment of water quality in river systems, the scientific community lacks efficient deterministic models able to simulate hydrological and biogeochemical processes in drainage networks at the regional scale, with high temporal resolution and water temperature explicitly determined. The model QUALity-NETwork (QUAL-NET was developed and tested on the Middle Loire River Corridor, a sub-catchment of the Loire River in France, prone to eutrophication. Hourly variations computed efficiently by the model helped disentangle the complex interactions existing between hydrological and biological processes across different timescales. Phosphorus (P availability was the most constraining factor for phytoplankton development in the Loire River, but simulating bacterial dynamics in QUAL-NET surprisingly evidenced large amounts of organic matter recycled within the water column through the microbial loop, which delivered significant fluxes of available P and enhanced phytoplankton growth. This explained why severe blooms still occur in the Loire River despite large P input reductions since 1990. QUAL-NET could be used to study past evolutions or predict future trajectories under climate change and land use scenarios.

  9. Harnessing diversity towards the reconstructing of large scale gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Takeshi Hase

    Full Text Available Elucidating gene regulatory network (GRN from large scale experimental data remains a central challenge in systems biology. Recently, numerous techniques, particularly consensus driven approaches combining different algorithms, have become a potentially promising strategy to infer accurate GRNs. Here, we develop a novel consensus inference algorithm, TopkNet that can integrate multiple algorithms to infer GRNs. Comprehensive performance benchmarking on a cloud computing framework demonstrated that (i a simple strategy to combine many algorithms does not always lead to performance improvement compared to the cost of consensus and (ii TopkNet integrating only high-performance algorithms provide significant performance improvement compared to the best individual algorithms and community prediction. These results suggest that a priori determination of high-performance algorithms is a key to reconstruct an unknown regulatory network. Similarity among gene-expression datasets can be useful to determine potential optimal algorithms for reconstruction of unknown regulatory networks, i.e., if expression-data associated with known regulatory network is similar to that with unknown regulatory network, optimal algorithms determined for the known regulatory network can be repurposed to infer the unknown regulatory network. Based on this observation, we developed a quantitative measure of similarity among gene-expression datasets and demonstrated that, if similarity between the two expression datasets is high, TopkNet integrating algorithms that are optimal for known dataset perform well on the unknown dataset. The consensus framework, TopkNet, together with the similarity measure proposed in this study provides a powerful strategy towards harnessing the wisdom of the crowds in reconstruction of unknown regulatory networks.

  10. Neural network models: from biology to many - body phenomenology

    International Nuclear Information System (INIS)

    Clark, J.W.

    1993-01-01

    Theoretical work in neural networks has a strange feel for most physicists. In some cases the aspect of design becomes paramount. More comfortable ground at least for many body theorists may be found in realistic biological simulation, although the complexity of most problems is so awesome that incisive results will be hard won. It has also shown the impressive capabilities of artificial networks in pattern recognition and classification may be exploited to solve management problems in experimental physics and for discovery of radically new theoretical description of physical systems. This advance represents an important step towards the ultimate goal of neuro biological paradigm. (A.B.)

  11. Network analysis reveals stage-specific changes in zebrafish embryo development using time course whole transcriptome profiling and prior biological knowledge.

    Science.gov (United States)

    Zhang, Yuji

    2015-01-01

    Molecular networks act as the backbone of molecular activities within cells, offering a unique opportunity to better understand the mechanism of diseases. While network data usually constitute only static network maps, integrating them with time course gene expression information can provide clues to the dynamic features of these networks and unravel the mechanistic driver genes characterizing cellular responses. Time course gene expression data allow us to broadly "watch" the dynamics of the system. However, one challenge in the analysis of such data is to establish and characterize the interplay among genes that are altered at different time points in the context of a biological process or functional category. Integrative analysis of these data sources will lead us a more complete understanding of how biological entities (e.g., genes and proteins) coordinately perform their biological functions in biological systems. In this paper, we introduced a novel network-based approach to extract functional knowledge from time-dependent biological processes at a system level using time course mRNA sequencing data in zebrafish embryo development. The proposed method was applied to investigate 1α, 25(OH)2D3-altered mechanisms in zebrafish embryo development. We applied the proposed method to a public zebrafish time course mRNA-Seq dataset, containing two different treatments along four time points. We constructed networks between gene ontology biological process categories, which were enriched in differential expressed genes between consecutive time points and different conditions. The temporal propagation of 1α, 25-Dihydroxyvitamin D3-altered transcriptional changes started from a few genes that were altered initially at earlier stage, to large groups of biological coherent genes at later stages. The most notable biological processes included neuronal and retinal development and generalized stress response. In addition, we also investigated the relationship among

  12. Group Centric Networking: Large Scale Over the Air Testing of Group Centric Networking

    Science.gov (United States)

    2016-11-01

    Large Scale Over-the-Air Testing of Group Centric Networking Logan Mercer, Greg Kuperman, Andrew Hunter, Brian Proulx MIT Lincoln Laboratory...performance of Group Centric Networking (GCN), a networking protocol developed for robust and scalable communications in lossy networks where users are...devices, and the ad-hoc nature of the network . Group Centric Networking (GCN) is a proposed networking protocol that addresses challenges specific to

  13. KeyPathwayMiner - De-novo network enrichment by combining multiple OMICS data and biological networks

    DEFF Research Database (Denmark)

    Baumbach, Jan; Alcaraz, Nicolas; Pauling, Josch K.

    We tackle the problem of de-novo pathway extraction. Given a biological network and a set of case-control studies, KeyPathwayMiner efficiently extracts and visualizes all maximal connected sub-networks that contain mainly genes that are dysregulated, e.g., differentially expressed, in most cases ...

  14. Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective

    Directory of Open Access Journals (Sweden)

    Shuo Gu

    2017-01-01

    Full Text Available With the rapid development of cheminformatics, computational biology, and systems biology, great progress has been made recently in the computational research of Chinese herbal medicine with in-depth understanding towards pharmacognosy. This paper summarized these studies in the aspects of computational methods, traditional Chinese medicine (TCM compound databases, and TCM network pharmacology. Furthermore, we chose arachidonic acid metabolic network as a case study to demonstrate the regulatory function of herbal medicine in the treatment of inflammation at network level. Finally, a computational workflow for the network-based TCM study, derived from our previous successful applications, was proposed.

  15. Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective.

    Science.gov (United States)

    Gu, Shuo; Pei, Jianfeng

    2017-01-01

    With the rapid development of cheminformatics, computational biology, and systems biology, great progress has been made recently in the computational research of Chinese herbal medicine with in-depth understanding towards pharmacognosy. This paper summarized these studies in the aspects of computational methods, traditional Chinese medicine (TCM) compound databases, and TCM network pharmacology. Furthermore, we chose arachidonic acid metabolic network as a case study to demonstrate the regulatory function of herbal medicine in the treatment of inflammation at network level. Finally, a computational workflow for the network-based TCM study, derived from our previous successful applications, was proposed.

  16. Multilayer network modeling creates opportunities for novel network statistics. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

    Science.gov (United States)

    Muldoon, Sarah Feldt

    2018-03-01

    As described in the review by Gosak et al., the field of network science has had enormous success in providing new insights into the structure and function of biological systems [1]. In the complex networks framework, system elements are network nodes, and connections between nodes represent some form of interaction between system elements [2]. The flexibility to define network nodes and edges to represent different aspects of biological systems has been employed to model numerous diverse systems at multiple scales.

  17. Continuum Modeling of Biological Network Formation

    KAUST Repository

    Albi, Giacomo

    2017-04-10

    We present an overview of recent analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transportation networks. The model describes the pressure field using a Darcy type equation and the dynamics of the conductance network under pressure force effects. Randomness in the material structure is represented by a linear diffusion term and conductance relaxation by an algebraic decay term. We first introduce micro- and mesoscopic models and show how they are connected to the macroscopic PDE system. Then, we provide an overview of analytical results for the PDE model, focusing mainly on the existence of weak and mild solutions and analysis of the steady states. The analytical part is complemented by extensive numerical simulations. We propose a discretization based on finite elements and study the qualitative properties of network structures for various parameter values.

  18. From biological neural networks to thinking machines: Transitioning biological organizational principles to computer technology

    Science.gov (United States)

    Ross, Muriel D.

    1991-01-01

    The three-dimensional organization of the vestibular macula is under study by computer assisted reconstruction and simulation methods as a model for more complex neural systems. One goal of this research is to transition knowledge of biological neural network architecture and functioning to computer technology, to contribute to the development of thinking computers. Maculas are organized as weighted neural networks for parallel distributed processing of information. The network is characterized by non-linearity of its terminal/receptive fields. Wiring appears to develop through constrained randomness. A further property is the presence of two main circuits, highly channeled and distributed modifying, that are connected through feedforward-feedback collaterals and biasing subcircuit. Computer simulations demonstrate that differences in geometry of the feedback (afferent) collaterals affects the timing and the magnitude of voltage changes delivered to the spike initiation zone. Feedforward (efferent) collaterals act as voltage followers and likely inhibit neurons of the distributed modifying circuit. These results illustrate the importance of feedforward-feedback loops, of timing, and of inhibition in refining neural network output. They also suggest that it is the distributed modifying network that is most involved in adaptation, memory, and learning. Tests of macular adaptation, through hyper- and microgravitational studies, support this hypothesis since synapses in the distributed modifying circuit, but not the channeled circuit, are altered. Transitioning knowledge of biological systems to computer technology, however, remains problematical.

  19. Aggregated Representation of Distribution Networks for Large-Scale Transmission Network Simulations

    DEFF Research Database (Denmark)

    Göksu, Ömer; Altin, Müfit; Sørensen, Poul Ejnar

    2014-01-01

    As a common practice of large-scale transmission network analysis the distribution networks have been represented as aggregated loads. However, with increasing share of distributed generation, especially wind and solar power, in the distribution networks, it became necessary to include...... the distributed generation within those analysis. In this paper a practical methodology to obtain aggregated behaviour of the distributed generation is proposed. The methodology, which is based on the use of the IEC standard wind turbine models, is applied on a benchmark distribution network via simulations....

  20. Quantitative assessment of biological impact using transcriptomic data and mechanistic network models

    International Nuclear Information System (INIS)

    Thomson, Ty M.; Sewer, Alain; Martin, Florian; Belcastro, Vincenzo; Frushour, Brian P.; Gebel, Stephan; Park, Jennifer; Schlage, Walter K.; Talikka, Marja; Vasilyev, Dmitry M.; Westra, Jurjen W.; Hoeng, Julia; Peitsch, Manuel C.

    2013-01-01

    Exposure to biologically active substances such as therapeutic drugs or environmental toxicants can impact biological systems at various levels, affecting individual molecules, signaling pathways, and overall cellular processes. The ability to derive mechanistic insights from the resulting system responses requires the integration of experimental measures with a priori knowledge about the system and the interacting molecules therein. We developed a novel systems biology-based methodology that leverages mechanistic network models and transcriptomic data to quantitatively assess the biological impact of exposures to active substances. Hierarchically organized network models were first constructed to provide a coherent framework for investigating the impact of exposures at the molecular, pathway and process levels. We then validated our methodology using novel and previously published experiments. For both in vitro systems with simple exposure and in vivo systems with complex exposures, our methodology was able to recapitulate known biological responses matching expected or measured phenotypes. In addition, the quantitative results were in agreement with experimental endpoint data for many of the mechanistic effects that were assessed, providing further objective confirmation of the approach. We conclude that our methodology evaluates the biological impact of exposures in an objective, systematic, and quantifiable manner, enabling the computation of a systems-wide and pan-mechanistic biological impact measure for a given active substance or mixture. Our results suggest that various fields of human disease research, from drug development to consumer product testing and environmental impact analysis, could benefit from using this methodology. - Highlights: • The impact of biologically active substances is quantified at multiple levels. • The systems-level impact integrates the perturbations of individual networks. • The networks capture the relationships between

  1. Visualization and Analysis of a Cardio Vascular Diseaseand MUPP1-related Biological Network combining Text Mining and Data Warehouse Approaches

    Directory of Open Access Journals (Sweden)

    Sommer Björn

    2010-03-01

    Full Text Available Detailed investigation of socially important diseases with modern experimental methods has resulted in the generation of large volume of valuable data. However, analysis and interpretation of this data needs application of efficient computational techniques and systems biology approaches. In particular, the techniques allowing the reconstruction of associative networks of various biological objects and events can be useful. In this publication, the combination of different techniques to create such a network associated with an abstract cell environment is discussed in order to gain insights into the functional as well as spatial interrelationships. It is shown that experimentally gained knowledge enriched with data warehouse content and text mining data can be used for the reconstruction and localization of a cardiovascular disease developing network beginning with MUPP1/MPDZ (multi-PDZ domain protein.

  2. Novel approaches to develop community-built biological network models for potential drug discovery.

    Science.gov (United States)

    Talikka, Marja; Bukharov, Natalia; Hayes, William S; Hofmann-Apitius, Martin; Alexopoulos, Leonidas; Peitsch, Manuel C; Hoeng, Julia

    2017-08-01

    Hundreds of thousands of data points are now routinely generated in clinical trials by molecular profiling and NGS technologies. A true translation of this data into knowledge is not possible without analysis and interpretation in a well-defined biology context. Currently, there are many public and commercial pathway tools and network models that can facilitate such analysis. At the same time, insights and knowledge that can be gained is highly dependent on the underlying biological content of these resources. Crowdsourcing can be employed to guarantee the accuracy and transparency of the biological content underlining the tools used to interpret rich molecular data. Areas covered: In this review, the authors describe crowdsourcing in drug discovery. The focal point is the efforts that have successfully used the crowdsourcing approach to verify and augment pathway tools and biological network models. Technologies that enable the building of biological networks with the community are also described. Expert opinion: A crowd of experts can be leveraged for the entire development process of biological network models, from ontologies to the evaluation of their mechanistic completeness. The ultimate goal is to facilitate biomarker discovery and personalized medicine by mechanistically explaining patients' differences with respect to disease prevention, diagnosis, and therapy outcome.

  3. Architecture and biological applications of artificial neural networks: a tuberculosis perspective.

    Science.gov (United States)

    Darsey, Jerry A; Griffin, William O; Joginipelli, Sravanthi; Melapu, Venkata Kiran

    2015-01-01

    Advancement of science and technology has prompted researchers to develop new intelligent systems that can solve a variety of problems such as pattern recognition, prediction, and optimization. The ability of the human brain to learn in a fashion that tolerates noise and error has attracted many researchers and provided the starting point for the development of artificial neural networks: the intelligent systems. Intelligent systems can acclimatize to the environment or data and can maximize the chances of success or improve the efficiency of a search. Due to massive parallelism with large numbers of interconnected processers and their ability to learn from the data, neural networks can solve a variety of challenging computational problems. Neural networks have the ability to derive meaning from complicated and imprecise data; they are used in detecting patterns, and trends that are too complex for humans, or other computer systems. Solutions to the toughest problems will not be found through one narrow specialization; therefore we need to combine interdisciplinary approaches to discover the solutions to a variety of problems. Many researchers in different disciplines such as medicine, bioinformatics, molecular biology, and pharmacology have successfully applied artificial neural networks. This chapter helps the reader in understanding the basics of artificial neural networks, their applications, and methodology; it also outlines the network learning process and architecture. We present a brief outline of the application of neural networks to medical diagnosis, drug discovery, gene identification, and protein structure prediction. We conclude with a summary of the results from our study on tuberculosis data using neural networks, in diagnosing active tuberculosis, and predicting chronic vs. infiltrative forms of tuberculosis.

  4. Biologically-inspired Learning in Pulsed Neural Networks

    DEFF Research Database (Denmark)

    Lehmann, Torsten; Woodburn, Robin

    1999-01-01

    Self-learning chips to implement many popular ANN (artificial neural network) algorithms are very difficult to design. We explain why this is so and say what lessons previous work teaches us in the design of self-learning systems. We offer a contribution to the `biologically-inspired' approach......, explaining what we mean by this term and providing an example of a robust, self-learning design that can solve simple classical-conditioning tasks. We give details of the design of individual circuits to perform component functions, which can then be combined into a network to solve the task. We argue...

  5. Logic-based models in systems biology: a predictive and parameter-free network analysis method†

    Science.gov (United States)

    Wynn, Michelle L.; Consul, Nikita; Merajver, Sofia D.

    2012-01-01

    Highly complex molecular networks, which play fundamental roles in almost all cellular processes, are known to be dysregulated in a number of diseases, most notably in cancer. As a consequence, there is a critical need to develop practical methodologies for constructing and analysing molecular networks at a systems level. Mathematical models built with continuous differential equations are an ideal methodology because they can provide a detailed picture of a network’s dynamics. To be predictive, however, differential equation models require that numerous parameters be known a priori and this information is almost never available. An alternative dynamical approach is the use of discrete logic-based models that can provide a good approximation of the qualitative behaviour of a biochemical system without the burden of a large parameter space. Despite their advantages, there remains significant resistance to the use of logic-based models in biology. Here, we address some common concerns and provide a brief tutorial on the use of logic-based models, which we motivate with biological examples. PMID:23072820

  6. BioCreative V track 4: a shared task for the extraction of causal network information using the Biological Expression Language.

    Science.gov (United States)

    Rinaldi, Fabio; Ellendorff, Tilia Renate; Madan, Sumit; Clematide, Simon; van der Lek, Adrian; Mevissen, Theo; Fluck, Juliane

    2016-01-01

    Automatic extraction of biological network information is one of the most desired and most complex tasks in biological and medical text mining. Track 4 at BioCreative V attempts to approach this complexity using fragments of large-scale manually curated biological networks, represented in Biological Expression Language (BEL), as training and test data. BEL is an advanced knowledge representation format which has been designed to be both human readable and machine processable. The specific goal of track 4 was to evaluate text mining systems capable of automatically constructing BEL statements from given evidence text, and of retrieving evidence text for given BEL statements. Given the complexity of the task, we designed an evaluation methodology which gives credit to partially correct statements. We identified various levels of information expressed by BEL statements, such as entities, functions, relations, and introduced an evaluation framework which rewards systems capable of delivering useful BEL fragments at each of these levels. The aim of this evaluation method is to help identify the characteristics of the systems which, if combined, would be most useful for achieving the overall goal of automatically constructing causal biological networks from text. © The Author(s) 2016. Published by Oxford University Press.

  7. On the rejection-based algorithm for simulation and analysis of large-scale reaction networks

    Energy Technology Data Exchange (ETDEWEB)

    Thanh, Vo Hong, E-mail: vo@cosbi.eu [The Microsoft Research-University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, Rovereto 38068 (Italy); Zunino, Roberto, E-mail: roberto.zunino@unitn.it [Department of Mathematics, University of Trento, Trento (Italy); Priami, Corrado, E-mail: priami@cosbi.eu [The Microsoft Research-University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, Rovereto 38068 (Italy); Department of Mathematics, University of Trento, Trento (Italy)

    2015-06-28

    Stochastic simulation for in silico studies of large biochemical networks requires a great amount of computational time. We recently proposed a new exact simulation algorithm, called the rejection-based stochastic simulation algorithm (RSSA) [Thanh et al., J. Chem. Phys. 141(13), 134116 (2014)], to improve simulation performance by postponing and collapsing as much as possible the propensity updates. In this paper, we analyze the performance of this algorithm in detail, and improve it for simulating large-scale biochemical reaction networks. We also present a new algorithm, called simultaneous RSSA (SRSSA), which generates many independent trajectories simultaneously for the analysis of the biochemical behavior. SRSSA improves simulation performance by utilizing a single data structure across simulations to select reaction firings and forming trajectories. The memory requirement for building and storing the data structure is thus independent of the number of trajectories. The updating of the data structure when needed is performed collectively in a single operation across the simulations. The trajectories generated by SRSSA are exact and independent of each other by exploiting the rejection-based mechanism. We test our new improvement on real biological systems with a wide range of reaction networks to demonstrate its applicability and efficiency.

  8. On-demand Overlay Networks for Large Scientific Data Transfers

    Energy Technology Data Exchange (ETDEWEB)

    Ramakrishnan, Lavanya [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Guok, Chin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Jackson, Keith [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Kissel, Ezra [Univ. of Delaware, Newark, DE (United States); Swany, D. Martin [Univ. of Delaware, Newark, DE (United States); Agarwal, Deborah [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2009-10-12

    Large scale scientific data transfers are central to scientific processes. Data from large experimental facilities have to be moved to local institutions for analysis or often data needs to be moved between local clusters and large supercomputing centers. In this paper, we propose and evaluate a network overlay architecture to enable highthroughput, on-demand, coordinated data transfers over wide-area networks. Our work leverages Phoebus and On-demand Secure Circuits and AdvanceReservation System (OSCARS) to provide high performance wide-area network connections. OSCARS enables dynamic provisioning of network paths with guaranteed bandwidth and Phoebus enables the coordination and effective utilization of the OSCARS network paths. Our evaluation shows that this approach leads to improved end-to-end data transfer throughput with minimal overheads. The achievedthroughput using our overlay was limited only by the ability of the end hosts to sink the data.

  9. Systems Biology Modeling of the Radiation Sensitivity Network: A Biomarker Discovery Platform

    International Nuclear Information System (INIS)

    Eschrich, Steven; Zhang Hongling; Zhao Haiyan; Boulware, David; Lee, Ji-Hyun; Bloom, Gregory; Torres-Roca, Javier F.

    2009-01-01

    Purpose: The discovery of effective biomarkers is a fundamental goal of molecular medicine. Developing a systems-biology understanding of radiosensitivity can enhance our ability of identifying radiation-specific biomarkers. Methods and Materials: Radiosensitivity, as represented by the survival fraction at 2 Gy was modeled in 48 human cancer cell lines. We applied a linear regression algorithm that integrates gene expression with biological variables, including ras status (mut/wt), tissue of origin and p53 status (mut/wt). Results: The biomarker discovery platform is a network representation of the top 500 genes identified by linear regression analysis. This network was reduced to a 10-hub network that includes c-Jun, HDAC1, RELA (p65 subunit of NFKB), PKC-beta, SUMO-1, c-Abl, STAT1, AR, CDK1, and IRF1. Nine targets associated with radiosensitization drugs are linked to the network, demonstrating clinical relevance. Furthermore, the model identified four significant radiosensitivity clusters of terms and genes. Ras was a dominant variable in the analysis, as was the tissue of origin, and their interaction with gene expression but not p53. Overrepresented biological pathways differed between clusters but included DNA repair, cell cycle, apoptosis, and metabolism. The c-Jun network hub was validated using a knockdown approach in 8 human cell lines representing lung, colon, and breast cancers. Conclusion: We have developed a novel radiation-biomarker discovery platform using a systems biology modeling approach. We believe this platform will play a central role in the integration of biology into clinical radiation oncology practice.

  10. Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective

    OpenAIRE

    Shuo Gu; Jianfeng Pei

    2017-01-01

    With the rapid development of cheminformatics, computational biology, and systems biology, great progress has been made recently in the computational research of Chinese herbal medicine with in-depth understanding towards pharmacognosy. This paper summarized these studies in the aspects of computational methods, traditional Chinese medicine (TCM) compound databases, and TCM network pharmacology. Furthermore, we chose arachidonic acid metabolic network as a case study to demonstrate the regula...

  11. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions.

    Science.gov (United States)

    Roy, Raktim; Shilpa, P Phani; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level. Systems biology-Microgravity-Pathways and networks-Bacteria. Astrobiology 16, 677-689.

  12. Biana: a software framework for compiling biological interactions and analyzing networks.

    Science.gov (United States)

    Garcia-Garcia, Javier; Guney, Emre; Aragues, Ramon; Planas-Iglesias, Joan; Oliva, Baldo

    2010-01-27

    The analysis and usage of biological data is hindered by the spread of information across multiple repositories and the difficulties posed by different nomenclature systems and storage formats. In particular, there is an important need for data unification in the study and use of protein-protein interactions. Without good integration strategies, it is difficult to analyze the whole set of available data and its properties. We introduce BIANA (Biologic Interactions and Network Analysis), a tool for biological information integration and network management. BIANA is a Python framework designed to achieve two major goals: i) the integration of multiple sources of biological information, including biological entities and their relationships, and ii) the management of biological information as a network where entities are nodes and relationships are edges. Moreover, BIANA uses properties of proteins and genes to infer latent biomolecular relationships by transferring edges to entities sharing similar properties. BIANA is also provided as a plugin for Cytoscape, which allows users to visualize and interactively manage the data. A web interface to BIANA providing basic functionalities is also available. The software can be downloaded under GNU GPL license from http://sbi.imim.es/web/BIANA.php. BIANA's approach to data unification solves many of the nomenclature issues common to systems dealing with biological data. BIANA can easily be extended to handle new specific data repositories and new specific data types. The unification protocol allows BIANA to be a flexible tool suitable for different user requirements: non-expert users can use a suggested unification protocol while expert users can define their own specific unification rules.

  13. Large-scale modeling of condition-specific gene regulatory networks by information integration and inference.

    Science.gov (United States)

    Ellwanger, Daniel Christian; Leonhardt, Jörn Florian; Mewes, Hans-Werner

    2014-12-01

    Understanding how regulatory networks globally coordinate the response of a cell to changing conditions, such as perturbations by shifting environments, is an elementary challenge in systems biology which has yet to be met. Genome-wide gene expression measurements are high dimensional as these are reflecting the condition-specific interplay of thousands of cellular components. The integration of prior biological knowledge into the modeling process of systems-wide gene regulation enables the large-scale interpretation of gene expression signals in the context of known regulatory relations. We developed COGERE (http://mips.helmholtz-muenchen.de/cogere), a method for the inference of condition-specific gene regulatory networks in human and mouse. We integrated existing knowledge of regulatory interactions from multiple sources to a comprehensive model of prior information. COGERE infers condition-specific regulation by evaluating the mutual dependency between regulator (transcription factor or miRNA) and target gene expression using prior information. This dependency is scored by the non-parametric, nonlinear correlation coefficient η(2) (eta squared) that is derived by a two-way analysis of variance. We show that COGERE significantly outperforms alternative methods in predicting condition-specific gene regulatory networks on simulated data sets. Furthermore, by inferring the cancer-specific gene regulatory network from the NCI-60 expression study, we demonstrate the utility of COGERE to promote hypothesis-driven clinical research. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Displacement and deformation measurement for large structures by camera network

    Science.gov (United States)

    Shang, Yang; Yu, Qifeng; Yang, Zhen; Xu, Zhiqiang; Zhang, Xiaohu

    2014-03-01

    A displacement and deformation measurement method for large structures by a series-parallel connection camera network is presented. By taking the dynamic monitoring of a large-scale crane in lifting operation as an example, a series-parallel connection camera network is designed, and the displacement and deformation measurement method by using this series-parallel connection camera network is studied. The movement range of the crane body is small, and that of the crane arm is large. The displacement of the crane body, the displacement of the crane arm relative to the body and the deformation of the arm are measured. Compared with a pure series or parallel connection camera network, the designed series-parallel connection camera network can be used to measure not only the movement and displacement of a large structure but also the relative movement and deformation of some interesting parts of the large structure by a relatively simple optical measurement system.

  15. Bridging the gap between clinicians and systems biologists: from network biology to translational biomedical research.

    Science.gov (United States)

    Jinawath, Natini; Bunbanjerdsuk, Sacarin; Chayanupatkul, Maneerat; Ngamphaiboon, Nuttapong; Asavapanumas, Nithi; Svasti, Jisnuson; Charoensawan, Varodom

    2016-11-22

    With the wealth of data accumulated from completely sequenced genomes and other high-throughput experiments, global studies of biological systems, by simultaneously investigating multiple biological entities (e.g. genes, transcripts, proteins), has become a routine. Network representation is frequently used to capture the presence of these molecules as well as their relationship. Network biology has been widely used in molecular biology and genetics, where several network properties have been shown to be functionally important. Here, we discuss how such methodology can be useful to translational biomedical research, where scientists traditionally focus on one or a small set of genes, diseases, and drug candidates at any one time. We first give an overview of network representation frequently used in biology: what nodes and edges represent, and review its application in preclinical research to date. Using cancer as an example, we review how network biology can facilitate system-wide approaches to identify targeted small molecule inhibitors. These types of inhibitors have the potential to be more specific, resulting in high efficacy treatments with less side effects, compared to the conventional treatments such as chemotherapy. Global analysis may provide better insight into the overall picture of human diseases, as well as identify previously overlooked problems, leading to rapid advances in medicine. From the clinicians' point of view, it is necessary to bridge the gap between theoretical network biology and practical biomedical research, in order to improve the diagnosis, prevention, and treatment of the world's major diseases.

  16. Topic modeling for cluster analysis of large biological and medical datasets.

    Science.gov (United States)

    Zhao, Weizhong; Zou, Wen; Chen, James J

    2014-01-01

    The big data moniker is nowhere better deserved than to describe the ever-increasing prodigiousness and complexity of biological and medical datasets. New methods are needed to generate and test hypotheses, foster biological interpretation, and build validated predictors. Although multivariate techniques such as cluster analysis may allow researchers to identify groups, or clusters, of related variables, the accuracies and effectiveness of traditional clustering methods diminish for large and hyper dimensional datasets. Topic modeling is an active research field in machine learning and has been mainly used as an analytical tool to structure large textual corpora for data mining. Its ability to reduce high dimensionality to a small number of latent variables makes it suitable as a means for clustering or overcoming clustering difficulties in large biological and medical datasets. In this study, three topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, are proposed and tested on the cluster analysis of three large datasets: Salmonella pulsed-field gel electrophoresis (PFGE) dataset, lung cancer dataset, and breast cancer dataset, which represent various types of large biological or medical datasets. All three various methods are shown to improve the efficacy/effectiveness of clustering results on the three datasets in comparison to traditional methods. A preferable cluster analysis method emerged for each of the three datasets on the basis of replicating known biological truths. Topic modeling could be advantageously applied to the large datasets of biological or medical research. The three proposed topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, yield clustering improvements for the three different data types. Clusters more efficaciously represent truthful groupings and subgroupings in the data than traditional methods, suggesting

  17. Selective vulnerability related to aging in large-scale resting brain networks.

    Science.gov (United States)

    Zhang, Hong-Ying; Chen, Wen-Xin; Jiao, Yun; Xu, Yao; Zhang, Xiang-Rong; Wu, Jing-Tao

    2014-01-01

    Normal aging is associated with cognitive decline. Evidence indicates that large-scale brain networks are affected by aging; however, it has not been established whether aging has equivalent effects on specific large-scale networks. In the present study, 40 healthy subjects including 22 older (aged 60-80 years) and 18 younger (aged 22-33 years) adults underwent resting-state functional MRI scanning. Four canonical resting-state networks, including the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN) and salience network, were extracted, and the functional connectivities in these canonical networks were compared between the younger and older groups. We found distinct, disruptive alterations present in the large-scale aging-related resting brain networks: the ECN was affected the most, followed by the DAN. However, the DMN and salience networks showed limited functional connectivity disruption. The visual network served as a control and was similarly preserved in both groups. Our findings suggest that the aged brain is characterized by selective vulnerability in large-scale brain networks. These results could help improve our understanding of the mechanism of degeneration in the aging brain. Additional work is warranted to determine whether selective alterations in the intrinsic networks are related to impairments in behavioral performance.

  18. A Reconfigurable and Biologically Inspired Paradigm for Computation Using Network-On-Chip and Spiking Neural Networks

    Directory of Open Access Journals (Sweden)

    Jim Harkin

    2009-01-01

    Full Text Available FPGA devices have emerged as a popular platform for the rapid prototyping of biological Spiking Neural Networks (SNNs applications, offering the key requirement of reconfigurability. However, FPGAs do not efficiently realise the biologically plausible neuron and synaptic models of SNNs, and current FPGA routing structures cannot accommodate the high levels of interneuron connectivity inherent in complex SNNs. This paper highlights and discusses the current challenges of implementing scalable SNNs on reconfigurable FPGAs. The paper proposes a novel field programmable neural network architecture (EMBRACE, incorporating low-power analogue spiking neurons, interconnected using a Network-on-Chip architecture. Results on the evaluation of the EMBRACE architecture using the XOR benchmark problem are presented, and the performance of the architecture is discussed. The paper also discusses the adaptability of the EMBRACE architecture in supporting fault tolerant computing.

  19. A Systems’ Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Xin Lai

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts.

  20. Biological instability in a chlorinated drinking water distribution network.

    Science.gov (United States)

    Nescerecka, Alina; Rubulis, Janis; Vital, Marius; Juhna, Talis; Hammes, Frederik

    2014-01-01

    The purpose of a drinking water distribution system is to deliver drinking water to the consumer, preferably with the same quality as when it left the treatment plant. In this context, the maintenance of good microbiological quality is often referred to as biological stability, and the addition of sufficient chlorine residuals is regarded as one way to achieve this. The full-scale drinking water distribution system of Riga (Latvia) was investigated with respect to biological stability in chlorinated drinking water. Flow cytometric (FCM) intact cell concentrations, intracellular adenosine tri-phosphate (ATP), heterotrophic plate counts and residual chlorine measurements were performed to evaluate the drinking water quality and stability at 49 sampling points throughout the distribution network. Cell viability methods were compared and the importance of extracellular ATP measurements was examined as well. FCM intact cell concentrations varied from 5×10(3) cells mL(-1) to 4.66×10(5) cells mL(-1) in the network. While this parameter did not exceed 2.1×10(4) cells mL(-1) in the effluent from any water treatment plant, 50% of all the network samples contained more than 1.06×10(5) cells mL(-1). This indisputably demonstrates biological instability in this particular drinking water distribution system, which was ascribed to a loss of disinfectant residuals and concomitant bacterial growth. The study highlights the potential of using cultivation-independent methods for the assessment of chlorinated water samples. In addition, it underlines the complexity of full-scale drinking water distribution systems, and the resulting challenges to establish the causes of biological instability.

  1. Comparative Analysis of Different Protocols to Manage Large Scale Networks

    OpenAIRE

    Anil Rao Pimplapure; Dr Jayant Dubey; Prashant Sen

    2013-01-01

    In recent year the numbers, complexity and size is increased in Large Scale Network. The best example of Large Scale Network is Internet, and recently once are Data-centers in Cloud Environment. In this process, involvement of several management tasks such as traffic monitoring, security and performance optimization is big task for Network Administrator. This research reports study the different protocols i.e. conventional protocols like Simple Network Management Protocol and newly Gossip bas...

  2. NAP: The Network Analysis Profiler, a web tool for easier topological analysis and comparison of medium-scale biological networks.

    Science.gov (United States)

    Theodosiou, Theodosios; Efstathiou, Georgios; Papanikolaou, Nikolas; Kyrpides, Nikos C; Bagos, Pantelis G; Iliopoulos, Ioannis; Pavlopoulos, Georgios A

    2017-07-14

    Nowadays, due to the technological advances of high-throughput techniques, Systems Biology has seen a tremendous growth of data generation. With network analysis, looking at biological systems at a higher level in order to better understand a system, its topology and the relationships between its components is of a great importance. Gene expression, signal transduction, protein/chemical interactions, biomedical literature co-occurrences, are few of the examples captured in biological network representations where nodes represent certain bioentities and edges represent the connections between them. Today, many tools for network visualization and analysis are available. Nevertheless, most of them are standalone applications that often (i) burden users with computing and calculation time depending on the network's size and (ii) focus on handling, editing and exploring a network interactively. While such functionality is of great importance, limited efforts have been made towards the comparison of the topological analysis of multiple networks. Network Analysis Provider (NAP) is a comprehensive web tool to automate network profiling and intra/inter-network topology comparison. It is designed to bridge the gap between network analysis, statistics, graph theory and partially visualization in a user-friendly way. It is freely available and aims to become a very appealing tool for the broader community. It hosts a great plethora of topological analysis methods such as node and edge rankings. Few of its powerful characteristics are: its ability to enable easy profile comparisons across multiple networks, find their intersection and provide users with simplified, high quality plots of any of the offered topological characteristics against any other within the same network. It is written in R and Shiny, it is based on the igraph library and it is able to handle medium-scale weighted/unweighted, directed/undirected and bipartite graphs. NAP is available at http://bioinformatics.med.uoc.gr/NAP .

  3. [Application of network biology on study of traditional Chinese medicine].

    Science.gov (United States)

    Tian, Sai-Sai; Yang, Jian; Zhao, Jing; Zhang, Wei-Dong

    2018-01-01

    With the completion of the human genome project, people have gradually recognized that the functions of the biological system are fulfilled through network-type interaction between genes, proteins and small molecules, while complex diseases are caused by the imbalance of biological processes due to a number of gene expression disorders. These have contributed to the rise of the concept of the "multi-target" drug discovery. Treatment and diagnosis of traditional Chinese medicine are based on holism and syndrome differentiation. At the molecular level, traditional Chinese medicine is characterized by multi-component and multi-target prescriptions, which is expected to provide a reference for the development of multi-target drugs. This paper reviews the application of network biology in traditional Chinese medicine in six aspects, in expectation to provide a reference to the modernized study of traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

  4. A biologically inspired neural network model to transformation invariant object recognition

    Science.gov (United States)

    Iftekharuddin, Khan M.; Li, Yaqin; Siddiqui, Faraz

    2007-09-01

    Transformation invariant image recognition has been an active research area due to its widespread applications in a variety of fields such as military operations, robotics, medical practices, geographic scene analysis, and many others. The primary goal for this research is detection of objects in the presence of image transformations such as changes in resolution, rotation, translation, scale and occlusion. We investigate a biologically-inspired neural network (NN) model for such transformation-invariant object recognition. In a classical training-testing setup for NN, the performance is largely dependent on the range of transformation or orientation involved in training. However, an even more serious dilemma is that there may not be enough training data available for successful learning or even no training data at all. To alleviate this problem, a biologically inspired reinforcement learning (RL) approach is proposed. In this paper, the RL approach is explored for object recognition with different types of transformations such as changes in scale, size, resolution and rotation. The RL is implemented in an adaptive critic design (ACD) framework, which approximates the neuro-dynamic programming of an action network and a critic network, respectively. Two ACD algorithms such as Heuristic Dynamic Programming (HDP) and Dual Heuristic dynamic Programming (DHP) are investigated to obtain transformation invariant object recognition. The two learning algorithms are evaluated statistically using simulated transformations in images as well as with a large-scale UMIST face database with pose variations. In the face database authentication case, the 90° out-of-plane rotation of faces from 20 different subjects in the UMIST database is used. Our simulations show promising results for both designs for transformation-invariant object recognition and authentication of faces. Comparing the two algorithms, DHP outperforms HDP in learning capability, as DHP takes fewer steps to

  5. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

    2006-01-01

    Systems biology focuses on obtaining a quantitative description of complete biological systems, even complete cellular function. In this way, it will be possible to perform computer-guided design of novel drugs, advanced therapies for treatment of complex diseases, and to perform in silico design....... Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and hence no single...... laboratory has access to all the necessary competences. For this reason the Yeast Systems Biology Network (YSBN) has been established. YSBN will coordinate research efforts, in yeast systems biology and, through the recently obtained EU funding for a Coordination Action, it will be possible to set...

  6. Seeded Bayesian Networks: Constructing genetic networks from microarray data

    Directory of Open Access Journals (Sweden)

    Quackenbush John

    2008-07-01

    Full Text Available Abstract Background DNA microarrays and other genomics-inspired technologies provide large datasets that often include hidden patterns of correlation between genes reflecting the complex processes that underlie cellular metabolism and physiology. The challenge in analyzing large-scale expression data has been to extract biologically meaningful inferences regarding these processes – often represented as networks – in an environment where the datasets are often imperfect and biological noise can obscure the actual signal. Although many techniques have been developed in an attempt to address these issues, to date their ability to extract meaningful and predictive network relationships has been limited. Here we describe a method that draws on prior information about gene-gene interactions to infer biologically relevant pathways from microarray data. Our approach consists of using preliminary networks derived from the literature and/or protein-protein interaction data as seeds for a Bayesian network analysis of microarray results. Results Through a bootstrap analysis of gene expression data derived from a number of leukemia studies, we demonstrate that seeded Bayesian Networks have the ability to identify high-confidence gene-gene interactions which can then be validated by comparison to other sources of pathway data. Conclusion The use of network seeds greatly improves the ability of Bayesian Network analysis to learn gene interaction networks from gene expression data. We demonstrate that the use of seeds derived from the biomedical literature or high-throughput protein-protein interaction data, or the combination, provides improvement over a standard Bayesian Network analysis, allowing networks involving dynamic processes to be deduced from the static snapshots of biological systems that represent the most common source of microarray data. Software implementing these methods has been included in the widely used TM4 microarray analysis package.

  7. Throughput Analysis of Large Wireless Networks with Regular Topologies

    Directory of Open Access Journals (Sweden)

    Hong Kezhu

    2007-01-01

    Full Text Available The throughput of large wireless networks with regular topologies is analyzed under two medium-access control schemes: synchronous array method (SAM and slotted ALOHA. The regular topologies considered are square, hexagon, and triangle. Both nonfading channels and Rayleigh fading channels are examined. Furthermore, both omnidirectional antennas and directional antennas are considered. Our analysis shows that the SAM leads to a much higher network throughput than the slotted ALOHA. The network throughput in this paper is measured in either bits-hops per second per Hertz per node or bits-meters per second per Hertz per node. The exact connection between the two measures is shown for each topology. With these two fundamental units, the network throughput shown in this paper can serve as a reliable benchmark for future works on network throughput of large networks.

  8. Throughput Analysis of Large Wireless Networks with Regular Topologies

    Directory of Open Access Journals (Sweden)

    Kezhu Hong

    2007-04-01

    Full Text Available The throughput of large wireless networks with regular topologies is analyzed under two medium-access control schemes: synchronous array method (SAM and slotted ALOHA. The regular topologies considered are square, hexagon, and triangle. Both nonfading channels and Rayleigh fading channels are examined. Furthermore, both omnidirectional antennas and directional antennas are considered. Our analysis shows that the SAM leads to a much higher network throughput than the slotted ALOHA. The network throughput in this paper is measured in either bits-hops per second per Hertz per node or bits-meters per second per Hertz per node. The exact connection between the two measures is shown for each topology. With these two fundamental units, the network throughput shown in this paper can serve as a reliable benchmark for future works on network throughput of large networks.

  9. Quantum Processes and Dynamic Networks in Physical and Biological Systems.

    Science.gov (United States)

    Dudziak, Martin Joseph

    Quantum theory since its earliest formulations in the Copenhagen Interpretation has been difficult to integrate with general relativity and with classical Newtonian physics. There has been traditionally a regard for quantum phenomena as being a limiting case for a natural order that is fundamentally classical except for microscopic extrema where quantum mechanics must be applied, more as a mathematical reconciliation rather than as a description and explanation. Macroscopic sciences including the study of biological neural networks, cellular energy transports and the broad field of non-linear and chaotic systems point to a quantum dimension extending across all scales of measurement and encompassing all of Nature as a fundamentally quantum universe. Theory and observation lead to a number of hypotheses all of which point to dynamic, evolving networks of fundamental or elementary processes as the underlying logico-physical structure (manifestation) in Nature and a strongly quantized dimension to macroscalar processes such as are found in biological, ecological and social systems. The fundamental thesis advanced and presented herein is that quantum phenomena may be the direct consequence of a universe built not from objects and substance but from interacting, interdependent processes collectively operating as sets and networks, giving rise to systems that on microcosmic or macroscopic scales function wholistically and organically, exhibiting non-locality and other non -classical phenomena. The argument is made that such effects as non-locality are not aberrations or departures from the norm but ordinary consequences of the process-network dynamics of Nature. Quantum processes are taken to be the fundamental action-events within Nature; rather than being the exception quantum theory is the rule. The argument is also presented that the study of quantum physics could benefit from the study of selective higher-scale complex systems, such as neural processes in the brain

  10. Experimental performance evaluation of software defined networking (SDN) based data communication networks for large scale flexi-grid optical networks.

    Science.gov (United States)

    Zhao, Yongli; He, Ruiying; Chen, Haoran; Zhang, Jie; Ji, Yuefeng; Zheng, Haomian; Lin, Yi; Wang, Xinbo

    2014-04-21

    Software defined networking (SDN) has become the focus in the current information and communication technology area because of its flexibility and programmability. It has been introduced into various network scenarios, such as datacenter networks, carrier networks, and wireless networks. Optical transport network is also regarded as an important application scenario for SDN, which is adopted as the enabling technology of data communication networks (DCN) instead of general multi-protocol label switching (GMPLS). However, the practical performance of SDN based DCN for large scale optical networks, which is very important for the technology selection in the future optical network deployment, has not been evaluated up to now. In this paper we have built a large scale flexi-grid optical network testbed with 1000 virtual optical transport nodes to evaluate the performance of SDN based DCN, including network scalability, DCN bandwidth limitation, and restoration time. A series of network performance parameters including blocking probability, bandwidth utilization, average lightpath provisioning time, and failure restoration time have been demonstrated under various network environments, such as with different traffic loads and different DCN bandwidths. The demonstration in this work can be taken as a proof for the future network deployment.

  11. A reverse engineering approach to optimize experiments for the construction of biological regulatory networks.

    Science.gov (United States)

    Zhang, Xiaomeng; Shao, Bin; Wu, Yangle; Qi, Ouyang

    2013-01-01

    One of the major objectives in systems biology is to understand the relation between the topological structures and the dynamics of biological regulatory networks. In this context, various mathematical tools have been developed to deduct structures of regulatory networks from microarray expression data. In general, from a single data set, one cannot deduct the whole network structure; additional expression data are usually needed. Thus how to design a microarray expression experiment in order to get the most information is a practical problem in systems biology. Here we propose three methods, namely, maximum distance method, trajectory entropy method, and sampling method, to derive the optimal initial conditions for experiments. The performance of these methods is tested and evaluated in three well-known regulatory networks (budding yeast cell cycle, fission yeast cell cycle, and E. coli. SOS network). Based on the evaluation, we propose an efficient strategy for the design of microarray expression experiments.

  12. A Novel CPU/GPU Simulation Environment for Large-Scale Biologically-Realistic Neural Modeling

    Directory of Open Access Journals (Sweden)

    Roger V Hoang

    2013-10-01

    Full Text Available Computational Neuroscience is an emerging field that provides unique opportunities to studycomplex brain structures through realistic neural simulations. However, as biological details are added tomodels, the execution time for the simulation becomes longer. Graphics Processing Units (GPUs are now being utilized to accelerate simulations due to their ability to perform computations in parallel. As such, they haveshown significant improvement in execution time compared to Central Processing Units (CPUs. Most neural simulators utilize either multiple CPUs or a single GPU for better performance, but still show limitations in execution time when biological details are not sacrificed. Therefore, we present a novel CPU/GPU simulation environment for large-scale biological networks,the NeoCortical Simulator version 6 (NCS6. NCS6 is a free, open-source, parallelizable, and scalable simula-tor, designed to run on clusters of multiple machines, potentially with high performance computing devicesin each of them. It has built-in leaky-integrate-and-fire (LIF and Izhikevich (IZH neuron models, but usersalso have the capability to design their own plug-in interface for different neuron types as desired. NCS6is currently able to simulate one million cells and 100 million synapses in quasi real time by distributing dataacross these heterogeneous clusters of CPUs and GPUs.

  13. Biological mechanisms beyond network analysis via mathematical modeling. Comment on "Network science of biological systems at different scales: A review" by Marko Gosak et al.

    Science.gov (United States)

    Pedersen, Morten Gram

    2018-03-01

    Methods from network theory are increasingly used in research spanning from engineering and computer science to psychology and the social sciences. In this issue, Gosak et al. [1] provide a thorough review of network science applications to biological systems ranging from the subcellular world via neuroscience to ecosystems, with special attention to the insulin-secreting beta-cells in pancreatic islets.

  14. A large deformation viscoelastic model for double-network hydrogels

    Science.gov (United States)

    Mao, Yunwei; Lin, Shaoting; Zhao, Xuanhe; Anand, Lallit

    2017-03-01

    We present a large deformation viscoelasticity model for recently synthesized double network hydrogels which consist of a covalently-crosslinked polyacrylamide network with long chains, and an ionically-crosslinked alginate network with short chains. Such double-network gels are highly stretchable and at the same time tough, because when stretched the crosslinks in the ionically-crosslinked alginate network rupture which results in distributed internal microdamage which dissipates a substantial amount of energy, while the configurational entropy of the covalently-crosslinked polyacrylamide network allows the gel to return to its original configuration after deformation. In addition to the large hysteresis during loading and unloading, these double network hydrogels also exhibit a substantial rate-sensitive response during loading, but exhibit almost no rate-sensitivity during unloading. These features of large hysteresis and asymmetric rate-sensitivity are quite different from the response of conventional hydrogels. We limit our attention to modeling the complex viscoelastic response of such hydrogels under isothermal conditions. Our model is restricted in the sense that we have limited our attention to conditions under which one might neglect any diffusion of the water in the hydrogel - as might occur when the gel has a uniform initial value of the concentration of water, and the mobility of the water molecules in the gel is low relative to the time scale of the mechanical deformation. We also do not attempt to model the final fracture of such double-network hydrogels.

  15. Natural language acquisition in large scale neural semantic networks

    Science.gov (United States)

    Ealey, Douglas

    This thesis puts forward the view that a purely signal- based approach to natural language processing is both plausible and desirable. By questioning the veracity of symbolic representations of meaning, it argues for a unified, non-symbolic model of knowledge representation that is both biologically plausible and, potentially, highly efficient. Processes to generate a grounded, neural form of this model-dubbed the semantic filter-are discussed. The combined effects of local neural organisation, coincident with perceptual maturation, are used to hypothesise its nature. This theoretical model is then validated in light of a number of fundamental neurological constraints and milestones. The mechanisms of semantic and episodic development that the model predicts are then used to explain linguistic properties, such as propositions and verbs, syntax and scripting. To mimic the growth of locally densely connected structures upon an unbounded neural substrate, a system is developed that can grow arbitrarily large, data- dependant structures composed of individual self- organising neural networks. The maturational nature of the data used results in a structure in which the perception of concepts is refined by the networks, but demarcated by subsequent structure. As a consequence, the overall structure shows significant memory and computational benefits, as predicted by the cognitive and neural models. Furthermore, the localised nature of the neural architecture also avoids the increasing error sensitivity and redundancy of traditional systems as the training domain grows. The semantic and episodic filters have been demonstrated to perform as well, or better, than more specialist networks, whilst using significantly larger vocabularies, more complex sentence forms and more natural corpora.

  16. Structural identifiability of cyclic graphical models of biological networks with latent variables.

    Science.gov (United States)

    Wang, Yulin; Lu, Na; Miao, Hongyu

    2016-06-13

    Graphical models have long been used to describe biological networks for a variety of important tasks such as the determination of key biological parameters, and the structure of graphical model ultimately determines whether such unknown parameters can be unambiguously obtained from experimental observations (i.e., the identifiability problem). Limited by resources or technical capacities, complex biological networks are usually partially observed in experiment, which thus introduces latent variables into the corresponding graphical models. A number of previous studies have tackled the parameter identifiability problem for graphical models such as linear structural equation models (SEMs) with or without latent variables. However, the limited resolution and efficiency of existing approaches necessarily calls for further development of novel structural identifiability analysis algorithms. An efficient structural identifiability analysis algorithm is developed in this study for a broad range of network structures. The proposed method adopts the Wright's path coefficient method to generate identifiability equations in forms of symbolic polynomials, and then converts these symbolic equations to binary matrices (called identifiability matrix). Several matrix operations are introduced for identifiability matrix reduction with system equivalency maintained. Based on the reduced identifiability matrices, the structural identifiability of each parameter is determined. A number of benchmark models are used to verify the validity of the proposed approach. Finally, the network module for influenza A virus replication is employed as a real example to illustrate the application of the proposed approach in practice. The proposed approach can deal with cyclic networks with latent variables. The key advantage is that it intentionally avoids symbolic computation and is thus highly efficient. Also, this method is capable of determining the identifiability of each single parameter and

  17. Automatic compilation from high-level biologically-oriented programming language to genetic regulatory networks.

    Science.gov (United States)

    Beal, Jacob; Lu, Ting; Weiss, Ron

    2011-01-01

    The field of synthetic biology promises to revolutionize our ability to engineer biological systems, providing important benefits for a variety of applications. Recent advances in DNA synthesis and automated DNA assembly technologies suggest that it is now possible to construct synthetic systems of significant complexity. However, while a variety of novel genetic devices and small engineered gene networks have been successfully demonstrated, the regulatory complexity of synthetic systems that have been reported recently has somewhat plateaued due to a variety of factors, including the complexity of biology itself and the lag in our ability to design and optimize sophisticated biological circuitry. To address the gap between DNA synthesis and circuit design capabilities, we present a platform that enables synthetic biologists to express desired behavior using a convenient high-level biologically-oriented programming language, Proto. The high level specification is compiled, using a regulatory motif based mechanism, to a gene network, optimized, and then converted to a computational simulation for numerical verification. Through several example programs we illustrate the automated process of biological system design with our platform, and show that our compiler optimizations can yield significant reductions in the number of genes (~ 50%) and latency of the optimized engineered gene networks. Our platform provides a convenient and accessible tool for the automated design of sophisticated synthetic biological systems, bridging an important gap between DNA synthesis and circuit design capabilities. Our platform is user-friendly and features biologically relevant compiler optimizations, providing an important foundation for the development of sophisticated biological systems.

  18. Community Detection for Large Graphs

    KAUST Repository

    Peng, Chengbin

    2014-05-04

    Many real world networks have inherent community structures, including social networks, transportation networks, biological networks, etc. For large scale networks with millions or billions of nodes in real-world applications, accelerating current community detection algorithms is in demand, and we present two approaches to tackle this issue -A K-core based framework that can accelerate existing community detection algorithms significantly; -A parallel inference algorithm via stochastic block models that can distribute the workload.

  19. Coarse-Grain Bandwidth Estimation Scheme for Large-Scale Network

    Science.gov (United States)

    Cheung, Kar-Ming; Jennings, Esther H.; Sergui, John S.

    2013-01-01

    A large-scale network that supports a large number of users can have an aggregate data rate of hundreds of Mbps at any time. High-fidelity simulation of a large-scale network might be too complicated and memory-intensive for typical commercial-off-the-shelf (COTS) tools. Unlike a large commercial wide-area-network (WAN) that shares diverse network resources among diverse users and has a complex topology that requires routing mechanism and flow control, the ground communication links of a space network operate under the assumption of a guaranteed dedicated bandwidth allocation between specific sparse endpoints in a star-like topology. This work solved the network design problem of estimating the bandwidths of a ground network architecture option that offer different service classes to meet the latency requirements of different user data types. In this work, a top-down analysis and simulation approach was created to size the bandwidths of a store-and-forward network for a given network topology, a mission traffic scenario, and a set of data types with different latency requirements. These techniques were used to estimate the WAN bandwidths of the ground links for different architecture options of the proposed Integrated Space Communication and Navigation (SCaN) Network. A new analytical approach, called the "leveling scheme," was developed to model the store-and-forward mechanism of the network data flow. The term "leveling" refers to the spreading of data across a longer time horizon without violating the corresponding latency requirement of the data type. Two versions of the leveling scheme were developed: 1. A straightforward version that simply spreads the data of each data type across the time horizon and doesn't take into account the interactions among data types within a pass, or between data types across overlapping passes at a network node, and is inherently sub-optimal. 2. Two-state Markov leveling scheme that takes into account the second order behavior of

  20. Environmental versatility promotes modularity in large scale metabolic networks

    OpenAIRE

    Samal A.; Wagner Andreas; Martin O.C.

    2011-01-01

    Abstract Background The ubiquity of modules in biological networks may result from an evolutionary benefit of a modular organization. For instance, modularity may increase the rate of adaptive evolution, because modules can be easily combined into new arrangements that may benefit their carrier. Conversely, modularity may emerge as a by-product of some trait. We here ask whether this last scenario may play a role in genome-scale metabolic networks that need to sustain life in one or more chem...

  1. Network cosmology.

    Science.gov (United States)

    Krioukov, Dmitri; Kitsak, Maksim; Sinkovits, Robert S; Rideout, David; Meyer, David; Boguñá, Marián

    2012-01-01

    Prediction and control of the dynamics of complex networks is a central problem in network science. Structural and dynamical similarities of different real networks suggest that some universal laws might accurately describe the dynamics of these networks, albeit the nature and common origin of such laws remain elusive. Here we show that the causal network representing the large-scale structure of spacetime in our accelerating universe is a power-law graph with strong clustering, similar to many complex networks such as the Internet, social, or biological networks. We prove that this structural similarity is a consequence of the asymptotic equivalence between the large-scale growth dynamics of complex networks and causal networks. This equivalence suggests that unexpectedly similar laws govern the dynamics of complex networks and spacetime in the universe, with implications to network science and cosmology.

  2. Large Whale Biology Survey (DE9908, EK500)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The large whale biology survey primarily focuses on right whales in the coastal and continental shelf areas, with the following objectives: 1) Develop a better...

  3. The Annotation, Mapping, Expression and Network (AMEN suite of tools for molecular systems biology

    Directory of Open Access Journals (Sweden)

    Primig Michael

    2008-02-01

    Full Text Available Abstract Background High-throughput genome biological experiments yield large and multifaceted datasets that require flexible and user-friendly analysis tools to facilitate their interpretation by life scientists. Many solutions currently exist, but they are often limited to specific steps in the complex process of data management and analysis and some require extensive informatics skills to be installed and run efficiently. Results We developed the Annotation, Mapping, Expression and Network (AMEN software as a stand-alone, unified suite of tools that enables biological and medical researchers with basic bioinformatics training to manage and explore genome annotation, chromosomal mapping, protein-protein interaction, expression profiling and proteomics data. The current version provides modules for (i uploading and pre-processing data from microarray expression profiling experiments, (ii detecting groups of significantly co-expressed genes, and (iii searching for enrichment of functional annotations within those groups. Moreover, the user interface is designed to simultaneously visualize several types of data such as protein-protein interaction networks in conjunction with expression profiles and cellular co-localization patterns. We have successfully applied the program to interpret expression profiling data from budding yeast, rodents and human. Conclusion AMEN is an innovative solution for molecular systems biological data analysis freely available under the GNU license. The program is available via a website at the Sourceforge portal which includes a user guide with concrete examples, links to external databases and helpful comments to implement additional functionalities. We emphasize that AMEN will continue to be developed and maintained by our laboratory because it has proven to be extremely useful for our genome biological research program.

  4. Annotating gene sets by mining large literature collections with protein networks.

    Science.gov (United States)

    Wang, Sheng; Ma, Jianzhu; Yu, Michael Ku; Zheng, Fan; Huang, Edward W; Han, Jiawei; Peng, Jian; Ideker, Trey

    2018-01-01

    Analysis of patient genomes and transcriptomes routinely recognizes new gene sets associated with human disease. Here we present an integrative natural language processing system which infers common functions for a gene set through automatic mining of the scientific literature with biological networks. This system links genes with associated literature phrases and combines these links with protein interactions in a single heterogeneous network. Multiscale functional annotations are inferred based on network distances between phrases and genes and then visualized as an ontology of biological concepts. To evaluate this system, we predict functions for gene sets representing known pathways and find that our approach achieves substantial improvement over the conventional text-mining baseline method. Moreover, our system discovers novel annotations for gene sets or pathways without previously known functions. Two case studies demonstrate how the system is used in discovery of new cancer-related pathways with ontological annotations.

  5. A biological network-based regularized artificial neural network model for robust phenotype prediction from gene expression data.

    Science.gov (United States)

    Kang, Tianyu; Ding, Wei; Zhang, Luoyan; Ziemek, Daniel; Zarringhalam, Kourosh

    2017-12-19

    Stratification of patient subpopulations that respond favorably to treatment or experience and adverse reaction is an essential step toward development of new personalized therapies and diagnostics. It is currently feasible to generate omic-scale biological measurements for all patients in a study, providing an opportunity for machine learning models to identify molecular markers for disease diagnosis and progression. However, the high variability of genetic background in human populations hampers the reproducibility of omic-scale markers. In this paper, we develop a biological network-based regularized artificial neural network model for prediction of phenotype from transcriptomic measurements in clinical trials. To improve model sparsity and the overall reproducibility of the model, we incorporate regularization for simultaneous shrinkage of gene sets based on active upstream regulatory mechanisms into the model. We benchmark our method against various regression, support vector machines and artificial neural network models and demonstrate the ability of our method in predicting the clinical outcomes using clinical trial data on acute rejection in kidney transplantation and response to Infliximab in ulcerative colitis. We show that integration of prior biological knowledge into the classification as developed in this paper, significantly improves the robustness and generalizability of predictions to independent datasets. We provide a Java code of our algorithm along with a parsed version of the STRING DB database. In summary, we present a method for prediction of clinical phenotypes using baseline genome-wide expression data that makes use of prior biological knowledge on gene-regulatory interactions in order to increase robustness and reproducibility of omic-scale markers. The integrated group-wise regularization methods increases the interpretability of biological signatures and gives stable performance estimates across independent test sets.

  6. MicroRNA functional network in pancreatic cancer: From biology to ...

    Indian Academy of Sciences (India)

    [Wang J and Sen S 2011 MicroRNA functional network in pancreatic cancer: From biology to biomarkers of disease. ... growth factor type I receptor; INSR, insulin receptor; IPA, Ingenuity Pathway Analysis; IPMN, ..... Prostate cancer signalling.

  7. The impact of network biology in pharmacology and toxicology

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Taboureau, Olivier

    2012-01-01

    With the need to investigate alternative approaches and emerging technologies in order to increase drug efficacy and reduce adverse drug effects, network biology offers a novel way of approaching drug discovery by considering the effect of a molecule and protein's function in a global physiological...... and tools that allow integration and analysis of such information for understanding the properties of small molecules in the context of cellular networks. With the recent advances in the omics area, global integrative approaches are necessary to cope with the massive amounts of data, and biomedical...

  8. Biological network extraction from scientific literature: state of the art and challenges.

    Science.gov (United States)

    Li, Chen; Liakata, Maria; Rebholz-Schuhmann, Dietrich

    2014-09-01

    Networks of molecular interactions explain complex biological processes, and all known information on molecular events is contained in a number of public repositories including the scientific literature. Metabolic and signalling pathways are often viewed separately, even though both types are composed of interactions involving proteins and other chemical entities. It is necessary to be able to combine data from all available resources to judge the functionality, complexity and completeness of any given network overall, but especially the full integration of relevant information from the scientific literature is still an ongoing and complex task. Currently, the text-mining research community is steadily moving towards processing the full body of the scientific literature by making use of rich linguistic features such as full text parsing, to extract biological interactions. The next step will be to combine these with information from scientific databases to support hypothesis generation for the discovery of new knowledge and the extension of biological networks. The generation of comprehensive networks requires technologies such as entity grounding, coordination resolution and co-reference resolution, which are not fully solved and are required to further improve the quality of results. Here, we analyse the state of the art for the extraction of network information from the scientific literature and the evaluation of extraction methods against reference corpora, discuss challenges involved and identify directions for future research. © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Evolution of a large online social network

    International Nuclear Information System (INIS)

    Hu Haibo; Wang Xiaofan

    2009-01-01

    Although recently there are extensive research on the collaborative networks and online communities, there is very limited knowledge about the actual evolution of the online social networks (OSN). In the Letter, we study the structural evolution of a large online virtual community. We find that the scale growth of the OSN shows non-trivial S shape which may provide a proper exemplification for Bass diffusion model. We reveal that the evolutions of many network properties, such as density, clustering, heterogeneity and modularity, show non-monotone feature, and shrink phenomenon occurs for the path length and diameter of the network. Furthermore, the OSN underwent a transition from degree assortativity characteristic of collaborative networks to degree disassortativity characteristic of many OSNs. Our study has revealed the evolutionary pattern of interpersonal interactions in a specific population and provided a valuable platform for theoretical modeling and further analysis

  10. PKI security in large-scale healthcare networks

    OpenAIRE

    Mantas, G.; Lymberopoulos, D.; Komninos, N.

    2012-01-01

    During the past few years a lot of PKI (Public Key Infrastructures) infrastructures have been proposed for healthcare networks in order to ensure secure communication services and exchange of data among healthcare professionals. However, there is a plethora of challenges in these healthcare PKI infrastructures. Especially, there are a lot of challenges for PKI infrastructures deployed over large-scale healthcare networks. In this paper, we propose a PKI infrastructure to ensure security in a ...

  11. Large area synchrotron X-ray fluorescence mapping of biological samples

    International Nuclear Information System (INIS)

    Kempson, I.; Thierry, B.; Smith, E.; Gao, M.; De Jonge, M.

    2014-01-01

    Large area mapping of inorganic material in biological samples has suffered severely from prohibitively long acquisition times. With the advent of new detector technology we can now generate statistically relevant information for studying cell populations, inter-variability and bioinorganic chemistry in large specimen. We have been implementing ultrafast synchrotron-based XRF mapping afforded by the MAIA detector for large area mapping of biological material. For example, a 2.5 million pixel map can be acquired in 3 hours, compared to a typical synchrotron XRF set-up needing over 1 month of uninterrupted beamtime. Of particular focus to us is the fate of metals and nanoparticles in cells, 3D tissue models and animal tissues. The large area scanning has for the first time provided statistically significant information on sufficiently large numbers of cells to provide data on intercellular variability in uptake of nanoparticles. Techniques such as flow cytometry generally require analysis of thousands of cells for statistically meaningful comparison, due to the large degree of variability. Large area XRF now gives comparable information in a quantifiable manner. Furthermore, we can now image localised deposition of nanoparticles in tissues that would be highly improbable to 'find' by typical XRF imaging. In addition, the ultra fast nature also makes it viable to conduct 3D XRF tomography over large dimensions. This technology avails new opportunities in biomonitoring and understanding metal and nanoparticle fate ex-vivo. Following from this is extension to molecular imaging through specific anti-body targeted nanoparticles to label specific tissues and monitor cellular process or biological consequence

  12. Integrated analysis of multiple data sources reveals modular structure of biological networks

    International Nuclear Information System (INIS)

    Lu Hongchao; Shi Baochen; Wu Gaowei; Zhang Yong; Zhu Xiaopeng; Zhang Zhihua; Liu Changning; Zhao, Yi; Wu Tao; Wang Jie; Chen Runsheng

    2006-01-01

    It has been a challenging task to integrate high-throughput data into investigations of the systematic and dynamic organization of biological networks. Here, we presented a simple hierarchical clustering algorithm that goes a long way to achieve this aim. Our method effectively reveals the modular structure of the yeast protein-protein interaction network and distinguishes protein complexes from functional modules by integrating high-throughput protein-protein interaction data with the added subcellular localization and expression profile data. Furthermore, we take advantage of the detected modules to provide a reliably functional context for the uncharacterized components within modules. On the other hand, the integration of various protein-protein association information makes our method robust to false-positives, especially for derived protein complexes. More importantly, this simple method can be extended naturally to other types of data fusion and provides a framework for the study of more comprehensive properties of the biological network and other forms of complex networks

  13. Survey of local and global biological network alignment: the need to reconcile the two sides of the same coin.

    Science.gov (United States)

    Guzzi, Pietro Hiram; Milenković, Tijana

    2017-01-05

    Analogous to genomic sequence alignment that allows for across-species transfer of biological knowledge between conserved sequence regions, biological network alignment can be used to guide the knowledge transfer between conserved regions of molecular networks of different species. Hence, biological network alignment can be used to redefine the traditional notion of a sequence-based homology to a new notion of network-based homology. Analogous to genomic sequence alignment, there exist local and global biological network alignments. Here, we survey prominent and recent computational approaches of each network alignment type and discuss their (dis)advantages. Then, as it was recently shown that the two approach types are complementary, in the sense that they capture different slices of cellular functioning, we discuss the need to reconcile the two network alignment types and present a recent first step in this direction. We conclude with some open research problems on this topic and comment on the usefulness of network alignment in other domains besides computational biology. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Using Agent Base Models to Optimize Large Scale Network for Large System Inventories

    Science.gov (United States)

    Shameldin, Ramez Ahmed; Bowling, Shannon R.

    2010-01-01

    The aim of this paper is to use Agent Base Models (ABM) to optimize large scale network handling capabilities for large system inventories and to implement strategies for the purpose of reducing capital expenses. The models used in this paper either use computational algorithms or procedure implementations developed by Matlab to simulate agent based models in a principal programming language and mathematical theory using clusters, these clusters work as a high performance computational performance to run the program in parallel computational. In both cases, a model is defined as compilation of a set of structures and processes assumed to underlie the behavior of a network system.

  15. Fast unfolding of communities in large networks

    International Nuclear Information System (INIS)

    Blondel, Vincent D; Guillaume, Jean-Loup; Lambiotte, Renaud; Lefebvre, Etienne

    2008-01-01

    We propose a simple method to extract the community structure of large networks. Our method is a heuristic method that is based on modularity optimization. It is shown to outperform all other known community detection methods in terms of computation time. Moreover, the quality of the communities detected is very good, as measured by the so-called modularity. This is shown first by identifying language communities in a Belgian mobile phone network of 2 million customers and by analysing a web graph of 118 million nodes and more than one billion links. The accuracy of our algorithm is also verified on ad hoc modular networks

  16. Safety evaluation of large ventilation networks

    International Nuclear Information System (INIS)

    Barrocas, M.; Pruchon, P.; Robin, J.P.; Rouyer, J.L.; Salmon, P.

    1981-01-01

    For large ventilation networks, it is necessary to make a safety evaluation of their responses to perturbations such as blower failure, unexpected transfers, local pressurization. This evaluation is not easy to perform because of the many interrelationships between the different parts of the networks, interrelationships coming from the circulations of workers and matetials between cells and rooms and from the usefulness of air transfers through zones of different classifications. This evaluation is all the more necessary since new imperatives in energy savings push for minimizing the air flows, which tends to render the network more sensitive to perturbations. A program to evaluate safety has been developed by the Service de Protection Technique in cooperation with operators and designers of big nuclear facilities and the first applications presented here show the weak points of the installation studied from the safety view point

  17. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    Rice, MaryJoe K; Ruder, Warren C

    2014-01-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems. (review)

  18. Creating biological nanomaterials using synthetic biology.

    Science.gov (United States)

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  19. New Visions for Large Scale Networks: Research and Applications

    Data.gov (United States)

    Networking and Information Technology Research and Development, Executive Office of the President — This paper documents the findings of the March 12-14, 2001 Workshop on New Visions for Large-Scale Networks: Research and Applications. The workshops objectives were...

  20. Learning Traffic as Images: A Deep Convolutional Neural Network for Large-Scale Transportation Network Speed Prediction.

    Science.gov (United States)

    Ma, Xiaolei; Dai, Zhuang; He, Zhengbing; Ma, Jihui; Wang, Yong; Wang, Yunpeng

    2017-04-10

    This paper proposes a convolutional neural network (CNN)-based method that learns traffic as images and predicts large-scale, network-wide traffic speed with a high accuracy. Spatiotemporal traffic dynamics are converted to images describing the time and space relations of traffic flow via a two-dimensional time-space matrix. A CNN is applied to the image following two consecutive steps: abstract traffic feature extraction and network-wide traffic speed prediction. The effectiveness of the proposed method is evaluated by taking two real-world transportation networks, the second ring road and north-east transportation network in Beijing, as examples, and comparing the method with four prevailing algorithms, namely, ordinary least squares, k-nearest neighbors, artificial neural network, and random forest, and three deep learning architectures, namely, stacked autoencoder, recurrent neural network, and long-short-term memory network. The results show that the proposed method outperforms other algorithms by an average accuracy improvement of 42.91% within an acceptable execution time. The CNN can train the model in a reasonable time and, thus, is suitable for large-scale transportation networks.

  1. Modeling Cancer Metastasis using Global, Quantitative and Integrative Network Biology

    DEFF Research Database (Denmark)

    Schoof, Erwin; Erler, Janine

    understanding of molecular processes which are fundamental to tumorigenesis. In Article 1, we propose a novel framework for how cancer mutations can be studied by taking into account their effect at the protein network level. In Article 2, we demonstrate how global, quantitative data on phosphorylation dynamics...... can be generated using MS, and how this can be modeled using a computational framework for deciphering kinase-substrate dynamics. This framework is described in depth in Article 3, and covers the design of KinomeXplorer, which allows the prediction of kinases responsible for modulating observed...... phosphorylation dynamics in a given biological sample. In Chapter III, we move into Integrative Network Biology, where, by combining two fundamental technologies (MS & NGS), we can obtain more in-depth insights into the links between cellular phenotype and genotype. Article 4 describes the proof...

  2. A Topology Visualization Early Warning Distribution Algorithm for Large-Scale Network Security Incidents

    Directory of Open Access Journals (Sweden)

    Hui He

    2013-01-01

    Full Text Available It is of great significance to research the early warning system for large-scale network security incidents. It can improve the network system’s emergency response capabilities, alleviate the cyber attacks’ damage, and strengthen the system’s counterattack ability. A comprehensive early warning system is presented in this paper, which combines active measurement and anomaly detection. The key visualization algorithm and technology of the system are mainly discussed. The large-scale network system’s plane visualization is realized based on the divide and conquer thought. First, the topology of the large-scale network is divided into some small-scale networks by the MLkP/CR algorithm. Second, the sub graph plane visualization algorithm is applied to each small-scale network. Finally, the small-scale networks’ topologies are combined into a topology based on the automatic distribution algorithm of force analysis. As the algorithm transforms the large-scale network topology plane visualization problem into a series of small-scale network topology plane visualization and distribution problems, it has higher parallelism and is able to handle the display of ultra-large-scale network topology.

  3. Deep Neural Networks: A New Framework for Modeling Biological Vision and Brain Information Processing.

    Science.gov (United States)

    Kriegeskorte, Nikolaus

    2015-11-24

    Recent advances in neural network modeling have enabled major strides in computer vision and other artificial intelligence applications. Human-level visual recognition abilities are coming within reach of artificial systems. Artificial neural networks are inspired by the brain, and their computations could be implemented in biological neurons. Convolutional feedforward networks, which now dominate computer vision, take further inspiration from the architecture of the primate visual hierarchy. However, the current models are designed with engineering goals, not to model brain computations. Nevertheless, initial studies comparing internal representations between these models and primate brains find surprisingly similar representational spaces. With human-level performance no longer out of reach, we are entering an exciting new era, in which we will be able to build biologically faithful feedforward and recurrent computational models of how biological brains perform high-level feats of intelligence, including vision.

  4. Main activities of the Latin American Network of Biological Dosimetry (LBDNet)

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Vallerga, M.B.; Radl, A.; Taja, M.R.; Stuck Oliveira, M.; Valdivia, P.; Garcia Lima, O.; Lamadrid, A.; Gonzalez Mesa, J.E.; Romero Aguilera, I.; Mandina Cardoso, T.; Guerrero Carbajal, C.; Arceo Maldonado, C.; Espinoza, M.; Martinez Lopez, W.; Di Tomasso, M.; Barquinero, F.; Roy, L.

    2010-01-01

    The Latin American Biological Dosimetry Network (LBDNET) was constituted in 2007 for mutual assistance in case of a radiation emergency in the region supported by IAEA Technical Cooperation Projects RLA/9/054 and RLA/9/061. The main objectives are: a) to strengthen the technical capacities of Biological Dosimetry Services belonging to laboratories existing in the region (Argentine, Brazil, Chile, Cuba, Mexico, Peru and Uruguay) integrated in National Radiological Emergency Plans to provide a rapid biodosimetric response in a coordinated manner between countries and with RANET-IAEA/BioDoseNet-WHO, b) to provide support to other countries in the region lacking Biological Dosimetry laboratories, c) to consolidate the organization of the Latin American Biological Dosimetry Network for mutual assistance. The activities developed include technical meetings for protocols and chromosomal aberration scoring criteria unification, blood samples cultures exercises, chromosomal aberrations analysis at microscope, discussion of statistical methods and specialized software for dose calculation, the intercomparison between laboratory data after the analysis of slides with irradiated material and the intercomparison of the analysis of captured images distributed electronically in the WEB. The last exercise was the transportation of an irradiated human blood sample to countries inside and outside of the region. At the moment the exercises are concluded and they are pending to be published in reference journals. Results obtained show the capacity in the region for a biodosimetric response to a radiological accident. In the future the network will integrate techniques for high dose exposure evaluation and will enhance the interaction with other emergency systems in the region. (authors) [es

  5. MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links.

    Science.gov (United States)

    Wathieu, Henri; Issa, Naiem T; Mohandoss, Manisha; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2017-01-01

    Cancer-associated metabolites result from cell-wide mechanisms of dysregulation. The field of metabolomics has sought to identify these aberrant metabolites as disease biomarkers, clues to understanding disease mechanisms, or even as therapeutic agents. This study was undertaken to reliably predict metabolites associated with colorectal, esophageal, and prostate cancers. Metabolite and disease biological action networks were compared in a computational platform called MSD-MAP (Multi Scale Disease-Metabolite Association Platform). Using differential gene expression analysis with patient-based RNAseq data from The Cancer Genome Atlas, genes up- or down-regulated in cancer compared to normal tissue were identified. Relational databases were used to map biological entities including pathways, functions, and interacting proteins, to those differential disease genes. Similar relational maps were built for metabolites, stemming from known and in silico predicted metabolite-protein associations. The hypergeometric test was used to find statistically significant relationships between disease and metabolite biological signatures at each tier, and metabolites were assessed for multi-scale association with each cancer. Metabolite networks were also directly associated with various other diseases using a disease functional perturbation database. Our platform recapitulated metabolite-disease links that have been empirically verified in the scientific literature, with network-based mapping of jointly-associated biological activity also matching known disease mechanisms. This was true for colorectal, esophageal, and prostate cancers, using metabolite action networks stemming from both predicted and known functional protein associations. By employing systems biology concepts, MSD-MAP reliably predicted known cancermetabolite links, and may serve as a predictive tool to streamline conventional metabolomic profiling methodologies. Copyright© Bentham Science Publishers; For any

  6. Biologically-inspired On-chip Learning in Pulsed Neural Networks

    DEFF Research Database (Denmark)

    Lehmann, Torsten; Woodburn, Robin

    1999-01-01

    Self-learning chips to implement many popular ANN (artificial neural network) algorithms are very difficult to design. We explain why this is so and say what lessons previous work teaches us in the design of self-learning systems. We offer a contribution to the "biologically-inspired" approach......, explaining what we mean by this term and providing an example of a robust, self-learning design that can solve simple classical-conditioning tasks, We give details of the design of individual circuits to perform component functions, which can then be combined into a network to solve the task. We argue...

  7. Attentional Networks and Biological Motion

    Directory of Open Access Journals (Sweden)

    Chandramouli Chandrasekaran

    2010-03-01

    Full Text Available Our ability to see meaningful actions when presented with pointlight traces of human movement is commonly referred to as the perception of biological motion. While traditionalexplanations have emphasized the spontaneous and automatic nature of this ability, morerecent findings suggest that attention may play a larger role than is typically assumed. Intwo studies we show that the speed and accuracy of responding to point-light stimuli is highly correlated with the ability to control selective attention. In our first experiment we measured thresholds for determining the walking direction of a masked point-light figure, and performance on a range of attention-related tasks in the same set of observers. Mask-density thresholds for the direction discrimination task varied quite considerably from observer to observer and this variation was highly correlated with performance on both Stroop and flanker interference tasks. Other components of attention, such as orienting, alerting and visual search efficiency, showed no such relationship. In a second experiment, we examined the relationship between the ability to determine the orientation of unmasked point-light actions and Stroop interference, again finding a strong correlation. Our results are consistent with previous research suggesting that biological motion processing may requite attention, and specifically implicate networks of attention related to executive control and selection.

  8. Non-Hermitian localization in biological networks.

    Science.gov (United States)

    Amir, Ariel; Hatano, Naomichi; Nelson, David R

    2016-04-01

    We explore the spectra and localization properties of the N-site banded one-dimensional non-Hermitian random matrices that arise naturally in sparse neural networks. Approximately equal numbers of random excitatory and inhibitory connections lead to spatially localized eigenfunctions and an intricate eigenvalue spectrum in the complex plane that controls the spontaneous activity and induced response. A finite fraction of the eigenvalues condense onto the real or imaginary axes. For large N, the spectrum has remarkable symmetries not only with respect to reflections across the real and imaginary axes but also with respect to 90^{∘} rotations, with an unusual anisotropic divergence in the localization length near the origin. When chains with periodic boundary conditions become directed, with a systematic directional bias superimposed on the randomness, a hole centered on the origin opens up in the density-of-states in the complex plane. All states are extended on the rim of this hole, while the localized eigenvalues outside the hole are unchanged. The bias-dependent shape of this hole tracks the bias-independent contours of constant localization length. We treat the large-N limit by a combination of direct numerical diagonalization and using transfer matrices, an approach that allows us to exploit an electrostatic analogy connecting the "charges" embodied in the eigenvalue distribution with the contours of constant localization length. We show that similar results are obtained for more realistic neural networks that obey "Dale's law" (each site is purely excitatory or inhibitory) and conclude with perturbation theory results that describe the limit of large directional bias, when all states are extended. Related problems arise in random ecological networks and in chains of artificial cells with randomly coupled gene expression patterns.

  9. Elucidation of time-dependent systems biology cell response patterns with time course network enrichment

    DEFF Research Database (Denmark)

    Wiwie, Christian; Rauch, Alexander; Haakonsson, Anders

    2018-01-01

    , no methods exist to integrate time series data with networks, thus preventing the identification of time-dependent systems biology responses. We close this gap with Time Course Network Enrichment (TiCoNE). It combines a new kind of human-augmented clustering with a novel approach to network enrichment...

  10. Base Station Placement Algorithm for Large-Scale LTE Heterogeneous Networks.

    Science.gov (United States)

    Lee, Seungseob; Lee, SuKyoung; Kim, Kyungsoo; Kim, Yoon Hyuk

    2015-01-01

    Data traffic demands in cellular networks today are increasing at an exponential rate, giving rise to the development of heterogeneous networks (HetNets), in which small cells complement traditional macro cells by extending coverage to indoor areas. However, the deployment of small cells as parts of HetNets creates a key challenge for operators' careful network planning. In particular, massive and unplanned deployment of base stations can cause high interference, resulting in highly degrading network performance. Although different mathematical modeling and optimization methods have been used to approach various problems related to this issue, most traditional network planning models are ill-equipped to deal with HetNet-specific characteristics due to their focus on classical cellular network designs. Furthermore, increased wireless data demands have driven mobile operators to roll out large-scale networks of small long term evolution (LTE) cells. Therefore, in this paper, we aim to derive an optimum network planning algorithm for large-scale LTE HetNets. Recently, attempts have been made to apply evolutionary algorithms (EAs) to the field of radio network planning, since they are characterized as global optimization methods. Yet, EA performance often deteriorates rapidly with the growth of search space dimensionality. To overcome this limitation when designing optimum network deployments for large-scale LTE HetNets, we attempt to decompose the problem and tackle its subcomponents individually. Particularly noting that some HetNet cells have strong correlations due to inter-cell interference, we propose a correlation grouping approach in which cells are grouped together according to their mutual interference. Both the simulation and analytical results indicate that the proposed solution outperforms the random-grouping based EA as well as an EA that detects interacting variables by monitoring the changes in the objective function algorithm in terms of system

  11. Predicting Positive and Negative Relationships in Large Social Networks.

    Directory of Open Access Journals (Sweden)

    Guan-Nan Wang

    Full Text Available In a social network, users hold and express positive and negative attitudes (e.g. support/opposition towards other users. Those attitudes exhibit some kind of binary relationships among the users, which play an important role in social network analysis. However, some of those binary relationships are likely to be latent as the scale of social network increases. The essence of predicting latent binary relationships have recently began to draw researchers' attention. In this paper, we propose a machine learning algorithm for predicting positive and negative relationships in social networks inspired by structural balance theory and social status theory. More specifically, we show that when two users in the network have fewer common neighbors, the prediction accuracy of the relationship between them deteriorates. Accordingly, in the training phase, we propose a segment-based training framework to divide the training data into two subsets according to the number of common neighbors between users, and build a prediction model for each subset based on support vector machine (SVM. Moreover, to deal with large-scale social network data, we employ a sampling strategy that selects small amount of training data while maintaining high accuracy of prediction. We compare our algorithm with traditional algorithms and adaptive boosting of them. Experimental results of typical data sets show that our algorithm can deal with large social networks and consistently outperforms other methods.

  12. Predicting Positive and Negative Relationships in Large Social Networks.

    Science.gov (United States)

    Wang, Guan-Nan; Gao, Hui; Chen, Lian; Mensah, Dennis N A; Fu, Yan

    2015-01-01

    In a social network, users hold and express positive and negative attitudes (e.g. support/opposition) towards other users. Those attitudes exhibit some kind of binary relationships among the users, which play an important role in social network analysis. However, some of those binary relationships are likely to be latent as the scale of social network increases. The essence of predicting latent binary relationships have recently began to draw researchers' attention. In this paper, we propose a machine learning algorithm for predicting positive and negative relationships in social networks inspired by structural balance theory and social status theory. More specifically, we show that when two users in the network have fewer common neighbors, the prediction accuracy of the relationship between them deteriorates. Accordingly, in the training phase, we propose a segment-based training framework to divide the training data into two subsets according to the number of common neighbors between users, and build a prediction model for each subset based on support vector machine (SVM). Moreover, to deal with large-scale social network data, we employ a sampling strategy that selects small amount of training data while maintaining high accuracy of prediction. We compare our algorithm with traditional algorithms and adaptive boosting of them. Experimental results of typical data sets show that our algorithm can deal with large social networks and consistently outperforms other methods.

  13. Robustness leads close to the edge of chaos in coupled map networks: toward the understanding of biological networks

    International Nuclear Information System (INIS)

    Saito, Nen; Kikuchi, Macoto

    2013-01-01

    Dynamics in biological networks are, in general, robust against several perturbations. We investigate a coupled map network as a model motivated by gene regulatory networks and design systems that are robust against phenotypic perturbations (perturbations in dynamics), as well as systems that are robust against mutation (perturbations in network structure). To achieve such a design, we apply a multicanonical Monte Carlo method. Analysis based on the maximum Lyapunov exponent and parameter sensitivity shows that systems with marginal stability, which are regarded as systems at the edge of chaos, emerge when robustness against network perturbations is required. This emergence of the edge of chaos is a self-organization phenomenon and does not need a fine tuning of parameters. (paper)

  14. Detecting and evaluating communities in complex human and biological networks

    Science.gov (United States)

    Morrison, Greg; Mahadevan, L.

    2012-02-01

    We develop a simple method for detecting the community structure in a network can by utilizing a measure of closeness between nodes. This approach readily leads to a method of coarse graining the network, which allows the detection of the natural hierarchy (or hierarchies) of community structure without appealing to an unknown resolution parameter. The closeness measure can also be used to evaluate the robustness of an individual node's assignment to its community (rather than evaluating only the quality of the global structure). Each of these methods in community detection and evaluation are illustrated using a variety of real world networks of either biological or sociological importance and illustrate the power and flexibility of the approach.

  15. Networks In Real Space: Characteristics and Analysis for Biology and Mechanics

    Science.gov (United States)

    Modes, Carl; Magnasco, Marcelo; Katifori, Eleni

    Functional networks embedded in physical space play a crucial role in countless biological and physical systems, from the efficient dissemination of oxygen, blood sugars, and hormonal signals in vascular systems to the complex relaying of informational signals in the brain to the distribution of stress and strain in architecture or static sand piles. Unlike their more-studied abstract cousins, such as the hyperlinked internet, social networks, or economic and financial connections, these networks are both constrained by and intimately connected to the physicality of their real, embedding space. We report on the results of new computational and analytic approaches tailored to these physical networks with particular implications and insights for mammalian organ vasculature.

  16. MODA: an efficient algorithm for network motif discovery in biological networks.

    Science.gov (United States)

    Omidi, Saeed; Schreiber, Falk; Masoudi-Nejad, Ali

    2009-10-01

    In recent years, interest has been growing in the study of complex networks. Since Erdös and Rényi (1960) proposed their random graph model about 50 years ago, many researchers have investigated and shaped this field. Many indicators have been proposed to assess the global features of networks. Recently, an active research area has developed in studying local features named motifs as the building blocks of networks. Unfortunately, network motif discovery is a computationally hard problem and finding rather large motifs (larger than 8 nodes) by means of current algorithms is impractical as it demands too much computational effort. In this paper, we present a new algorithm (MODA) that incorporates techniques such as a pattern growth approach for extracting larger motifs efficiently. We have tested our algorithm and found it able to identify larger motifs with more than 8 nodes more efficiently than most of the current state-of-the-art motif discovery algorithms. While most of the algorithms rely on induced subgraphs as motifs of the networks, MODA is able to extract both induced and non-induced subgraphs simultaneously. The MODA source code is freely available at: http://LBB.ut.ac.ir/Download/LBBsoft/MODA/

  17. From systems biology to photosynthesis and whole-plant physiology: a conceptual model for integrating multi-scale networks.

    Science.gov (United States)

    Weston, David J; Hanson, Paul J; Norby, Richard J; Tuskan, Gerald A; Wullschleger, Stan D

    2012-02-01

    Network analysis is now a common statistical tool for molecular biologists. Network algorithms are readily used to model gene, protein and metabolic correlations providing insight into pathways driving biological phenomenon. One output from such an analysis is a candidate gene list that can be responsible, in part, for the biological process of interest. The question remains, however, as to whether molecular network analysis can be used to inform process models at higher levels of biological organization. In our previous work, transcriptional networks derived from three plant species were constructed, interrogated for orthology and then correlated with photosynthetic inhibition at elevated temperature. One unique aspect of that study was the link from co-expression networks to net photosynthesis. In this addendum, we propose a conceptual model where traditional network analysis can be linked to whole-plant models thereby informing predictions on key processes such as photosynthesis, nutrient uptake and assimilation, and C partitioning.

  18. Pythoscape: A framework for generation of large protein similarity networks

    OpenAIRE

    Babbitt, Patricia; Barber, AE; Babbitt, PC

    2012-01-01

    Pythoscape is a framework implemented in Python for processing large protein similarity networks for visualization in other software packages. Protein similarity networks are graphical representations of sequence, structural and other similarities among pr

  19. Integrative analysis of many weighted co-expression networks using tensor computation.

    Directory of Open Access Journals (Sweden)

    Wenyuan Li

    2011-06-01

    Full Text Available The rapid accumulation of biological networks poses new challenges and calls for powerful integrative analysis tools. Most existing methods capable of simultaneously analyzing a large number of networks were primarily designed for unweighted networks, and cannot easily be extended to weighted networks. However, it is known that transforming weighted into unweighted networks by dichotomizing the edges of weighted networks with a threshold generally leads to information loss. We have developed a novel, tensor-based computational framework for mining recurrent heavy subgraphs in a large set of massive weighted networks. Specifically, we formulate the recurrent heavy subgraph identification problem as a heavy 3D subtensor discovery problem with sparse constraints. We describe an effective approach to solving this problem by designing a multi-stage, convex relaxation protocol, and a non-uniform edge sampling technique. We applied our method to 130 co-expression networks, and identified 11,394 recurrent heavy subgraphs, grouped into 2,810 families. We demonstrated that the identified subgraphs represent meaningful biological modules by validating against a large set of compiled biological knowledge bases. We also showed that the likelihood for a heavy subgraph to be meaningful increases significantly with its recurrence in multiple networks, highlighting the importance of the integrative approach to biological network analysis. Moreover, our approach based on weighted graphs detects many patterns that would be overlooked using unweighted graphs. In addition, we identified a large number of modules that occur predominately under specific phenotypes. This analysis resulted in a genome-wide mapping of gene network modules onto the phenome. Finally, by comparing module activities across many datasets, we discovered high-order dynamic cooperativeness in protein complex networks and transcriptional regulatory networks.

  20. Artificial neural network modelling

    CERN Document Server

    Samarasinghe, Sandhya

    2016-01-01

    This book covers theoretical aspects as well as recent innovative applications of Artificial Neural networks (ANNs) in natural, environmental, biological, social, industrial and automated systems. It presents recent results of ANNs in modelling small, large and complex systems under three categories, namely, 1) Networks, Structure Optimisation, Robustness and Stochasticity 2) Advances in Modelling Biological and Environmental Systems and 3) Advances in Modelling Social and Economic Systems. The book aims at serving undergraduates, postgraduates and researchers in ANN computational modelling. .

  1. An novel frequent probability pattern mining algorithm based on circuit simulation method in uncertain biological networks

    Science.gov (United States)

    2014-01-01

    Background Motif mining has always been a hot research topic in bioinformatics. Most of current research on biological networks focuses on exact motif mining. However, due to the inevitable experimental error and noisy data, biological network data represented as the probability model could better reflect the authenticity and biological significance, therefore, it is more biological meaningful to discover probability motif in uncertain biological networks. One of the key steps in probability motif mining is frequent pattern discovery which is usually based on the possible world model having a relatively high computational complexity. Methods In this paper, we present a novel method for detecting frequent probability patterns based on circuit simulation in the uncertain biological networks. First, the partition based efficient search is applied to the non-tree like subgraph mining where the probability of occurrence in random networks is small. Then, an algorithm of probability isomorphic based on circuit simulation is proposed. The probability isomorphic combines the analysis of circuit topology structure with related physical properties of voltage in order to evaluate the probability isomorphism between probability subgraphs. The circuit simulation based probability isomorphic can avoid using traditional possible world model. Finally, based on the algorithm of probability subgraph isomorphism, two-step hierarchical clustering method is used to cluster subgraphs, and discover frequent probability patterns from the clusters. Results The experiment results on data sets of the Protein-Protein Interaction (PPI) networks and the transcriptional regulatory networks of E. coli and S. cerevisiae show that the proposed method can efficiently discover the frequent probability subgraphs. The discovered subgraphs in our study contain all probability motifs reported in the experiments published in other related papers. Conclusions The algorithm of probability graph isomorphism

  2. Analysis of complex networks from biology to linguistics

    CERN Document Server

    Dehmer, Matthias

    2009-01-01

    Mathematical problems such as graph theory problems are of increasing importance for the analysis of modelling data in biomedical research such as in systems biology, neuronal network modelling etc. This book follows a new approach of including graph theory from a mathematical perspective with specific applications of graph theory in biomedical and computational sciences. The book is written by renowned experts in the field and offers valuable background information for a wide audience.

  3. Large deformation behavior of fat crystal networks

    NARCIS (Netherlands)

    Kloek, W.; Vliet, van T.; Walstra, P.

    2005-01-01

    Compression and wire-cutting experiments on dispersions of fully hydrogenated palm oil in sunflower oil with varying fraction solid fat were carried out to establish which parameters are important for the large deformation behavior of fat crystal networks. Compression experiments showed that the

  4. Find_tfSBP: find thermodynamics-feasible and smallest balanced pathways with high yield from large-scale metabolic networks.

    Science.gov (United States)

    Xu, Zixiang; Sun, Jibin; Wu, Qiaqing; Zhu, Dunming

    2017-12-11

    Biologically meaningful metabolic pathways are important references in the design of industrial bacterium. At present, constraint-based method is the only way to model and simulate a genome-scale metabolic network under steady-state criteria. Due to the inadequate assumption of the relationship in gene-enzyme-reaction as one-to-one unique association, computational difficulty or ignoring the yield from substrate to product, previous pathway finding approaches can't be effectively applied to find out the high yield pathways that are mass balanced in stoichiometry. In addition, the shortest pathways may not be the pathways with high yield. At the same time, a pathway, which exists in stoichiometry, may not be feasible in thermodynamics. By using mixed integer programming strategy, we put forward an algorithm to identify all the smallest balanced pathways which convert the source compound to the target compound in large-scale metabolic networks. The resulting pathways by our method can finely satisfy the stoichiometric constraints and non-decomposability condition. Especially, the functions of high yield and thermodynamics feasibility have been considered in our approach. This tool is tailored to direct the metabolic engineering practice to enlarge the metabolic potentials of industrial strains by integrating the extensive metabolic network information built from systems biology dataset.

  5. A swarm intelligence framework for reconstructing gene networks: searching for biologically plausible architectures.

    Science.gov (United States)

    Kentzoglanakis, Kyriakos; Poole, Matthew

    2012-01-01

    In this paper, we investigate the problem of reverse engineering the topology of gene regulatory networks from temporal gene expression data. We adopt a computational intelligence approach comprising swarm intelligence techniques, namely particle swarm optimization (PSO) and ant colony optimization (ACO). In addition, the recurrent neural network (RNN) formalism is employed for modeling the dynamical behavior of gene regulatory systems. More specifically, ACO is used for searching the discrete space of network architectures and PSO for searching the corresponding continuous space of RNN model parameters. We propose a novel solution construction process in the context of ACO for generating biologically plausible candidate architectures. The objective is to concentrate the search effort into areas of the structure space that contain architectures which are feasible in terms of their topological resemblance to real-world networks. The proposed framework is initially applied to the reconstruction of a small artificial network that has previously been studied in the context of gene network reverse engineering. Subsequently, we consider an artificial data set with added noise for reconstructing a subnetwork of the genetic interaction network of S. cerevisiae (yeast). Finally, the framework is applied to a real-world data set for reverse engineering the SOS response system of the bacterium Escherichia coli. Results demonstrate the relative advantage of utilizing problem-specific knowledge regarding biologically plausible structural properties of gene networks over conducting a problem-agnostic search in the vast space of network architectures.

  6. Exploitation of complex network topology for link prediction in biological interactomes

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-01-01

    In this work, we propose three novel and powerful approaches for the prediction of interactions in biological networks and conclude that it is possible to mine the topology of these complex system representations and produce reliable

  7. Stochastic noncooperative and cooperative evolutionary game strategies of a population of biological networks under natural selection.

    Science.gov (United States)

    Chen, Bor-Sen; Yeh, Chin-Hsun

    2017-12-01

    We review current static and dynamic evolutionary game strategies of biological networks and discuss the lack of random genetic variations and stochastic environmental disturbances in these models. To include these factors, a population of evolving biological networks is modeled as a nonlinear stochastic biological system with Poisson-driven genetic variations and random environmental fluctuations (stimuli). To gain insight into the evolutionary game theory of stochastic biological networks under natural selection, the phenotypic robustness and network evolvability of noncooperative and cooperative evolutionary game strategies are discussed from a stochastic Nash game perspective. The noncooperative strategy can be transformed into an equivalent multi-objective optimization problem and is shown to display significantly improved network robustness to tolerate genetic variations and buffer environmental disturbances, maintaining phenotypic traits for longer than the cooperative strategy. However, the noncooperative case requires greater effort and more compromises between partly conflicting players. Global linearization is used to simplify the problem of solving nonlinear stochastic evolutionary games. Finally, a simple stochastic evolutionary model of a metabolic pathway is simulated to illustrate the procedure of solving for two evolutionary game strategies and to confirm and compare their respective characteristics in the evolutionary process. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Network Expansion and Pathway Enrichment Analysis towards Biologically Significant Findings from Microarrays

    Directory of Open Access Journals (Sweden)

    Wu Xiaogang

    2012-06-01

    Full Text Available In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease, and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI database, and pathway enrichment from the human pathway database (HPD. We use a recently-published microarray dataset (GSE24215 related to insulin resistance and type 2 diabetes (T2D as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.

  9. Integration and segregation of large-scale brain networks during short-term task automatization.

    Science.gov (United States)

    Mohr, Holger; Wolfensteller, Uta; Betzel, Richard F; Mišić, Bratislav; Sporns, Olaf; Richiardi, Jonas; Ruge, Hannes

    2016-11-03

    The human brain is organized into large-scale functional networks that can flexibly reconfigure their connectivity patterns, supporting both rapid adaptive control and long-term learning processes. However, it has remained unclear how short-term network dynamics support the rapid transformation of instructions into fluent behaviour. Comparing fMRI data of a learning sample (N=70) with a control sample (N=67), we find that increasingly efficient task processing during short-term practice is associated with a reorganization of large-scale network interactions. Practice-related efficiency gains are facilitated by enhanced coupling between the cingulo-opercular network and the dorsal attention network. Simultaneously, short-term task automatization is accompanied by decreasing activation of the fronto-parietal network, indicating a release of high-level cognitive control, and a segregation of the default mode network from task-related networks. These findings suggest that short-term task automatization is enabled by the brain's ability to rapidly reconfigure its large-scale network organization involving complementary integration and segregation processes.

  10. Large photonic band gaps and strong attenuations of two-segment-connected Peano derivative networks

    International Nuclear Information System (INIS)

    Lu, Jian; Yang, Xiangbo; Zhang, Guogang; Cai, Lianzhang

    2011-01-01

    In this Letter, based on ancient Peano curves we construct four kinds of interesting Peano derivative networks composed of one-dimensional (1D) waveguides and investigate the optical transmission spectra and photonic attenuation behavior of electromagnetic (EM) waves in one- and two-segment-connected networks. It is found that for some two-segment-connected networks large photonic band gaps (PBGs) can be created and the widths of large PBGs can be controlled by adjusting the matching ratio of waveguide length and are insensitive to generation number. Diamond- and hexagon-Peano networks are good selectable structures for the designing of optical devices with large PBG(s) and strong attenuation(s). -- Highlights: → Peano and Peano derivative networks composed of 1D waveguides are designed. → Large PBGs with strong attenuations have been created by these fractal networks. → New approach for designing optical devices with large PBGs is proposed. → Diamond- and hexagon-Peano networks with d2:d1=2:1 are good selectable structures.

  11. Combined Model of Intrinsic and Extrinsic Variability for Computational Network Design with Application to Synthetic Biology

    Science.gov (United States)

    Toni, Tina; Tidor, Bruce

    2013-01-01

    Biological systems are inherently variable, with their dynamics influenced by intrinsic and extrinsic sources. These systems are often only partially characterized, with large uncertainties about specific sources of extrinsic variability and biochemical properties. Moreover, it is not yet well understood how different sources of variability combine and affect biological systems in concert. To successfully design biomedical therapies or synthetic circuits with robust performance, it is crucial to account for uncertainty and effects of variability. Here we introduce an efficient modeling and simulation framework to study systems that are simultaneously subject to multiple sources of variability, and apply it to make design decisions on small genetic networks that play a role of basic design elements of synthetic circuits. Specifically, the framework was used to explore the effect of transcriptional and post-transcriptional autoregulation on fluctuations in protein expression in simple genetic networks. We found that autoregulation could either suppress or increase the output variability, depending on specific noise sources and network parameters. We showed that transcriptional autoregulation was more successful than post-transcriptional in suppressing variability across a wide range of intrinsic and extrinsic magnitudes and sources. We derived the following design principles to guide the design of circuits that best suppress variability: (i) high protein cooperativity and low miRNA cooperativity, (ii) imperfect complementarity between miRNA and mRNA was preferred to perfect complementarity, and (iii) correlated expression of mRNA and miRNA – for example, on the same transcript – was best for suppression of protein variability. Results further showed that correlations in kinetic parameters between cells affected the ability to suppress variability, and that variability in transient states did not necessarily follow the same principles as variability in the steady

  12. Molecular codes in biological and chemical reaction networks.

    Directory of Open Access Journals (Sweden)

    Dennis Görlich

    Full Text Available Shannon's theory of communication has been very successfully applied for the analysis of biological information. However, the theory neglects semantic and pragmatic aspects and thus cannot directly be applied to distinguish between (bio- chemical systems able to process "meaningful" information from those that do not. Here, we present a formal method to assess a system's semantic capacity by analyzing a reaction network's capability to implement molecular codes. We analyzed models of chemical systems (martian atmosphere chemistry and various combustion chemistries, biochemical systems (gene expression, gene translation, and phosphorylation signaling cascades, an artificial chemistry, and random reaction networks. Our study suggests that different chemical systems possess different semantic capacities. No semantic capacity was found in the model of the martian atmosphere chemistry, the studied combustion chemistries, and highly connected random networks, i.e. with these chemistries molecular codes cannot be implemented. High semantic capacity was found in the studied biochemical systems and in random reaction networks where the number of second order reactions is twice the number of species. We conclude that our approach can be applied to evaluate the information processing capabilities of a chemical system and may thus be a useful tool to understand the origin and evolution of meaningful information, e.g. in the context of the origin of life.

  13. Quick Mining of Isomorphic Exact Large Patterns from Large Graphs

    KAUST Repository

    Almasri, Islam

    2014-12-01

    The applications of the sub graph isomorphism search are growing with the growing number of areas that model their systems using graphs or networks. Specifically, many biological systems, such as protein interaction networks, molecular structures and protein contact maps, are modeled as graphs. The sub graph isomorphism search is concerned with finding all sub graphs that are isomorphic to a relevant query graph, the existence of such sub graphs can reflect on the characteristics of the modeled system. The most computationally expensive step in the search for isomorphic sub graphs is the backtracking algorithm that traverses the nodes of the target graph. In this paper, we propose a pruning approach that is inspired by the minimum remaining value heuristic that achieves greater scalability over large query and target graphs. Our testing on various biological networks shows that performance enhancement of our approach over existing state-of-the-art approaches varies between 6x and 53x. © 2014 IEEE.

  14. Quick Mining of Isomorphic Exact Large Patterns from Large Graphs

    KAUST Repository

    Almasri, Islam; Gao, Xin; Fedoroff, Nina V.

    2014-01-01

    The applications of the sub graph isomorphism search are growing with the growing number of areas that model their systems using graphs or networks. Specifically, many biological systems, such as protein interaction networks, molecular structures and protein contact maps, are modeled as graphs. The sub graph isomorphism search is concerned with finding all sub graphs that are isomorphic to a relevant query graph, the existence of such sub graphs can reflect on the characteristics of the modeled system. The most computationally expensive step in the search for isomorphic sub graphs is the backtracking algorithm that traverses the nodes of the target graph. In this paper, we propose a pruning approach that is inspired by the minimum remaining value heuristic that achieves greater scalability over large query and target graphs. Our testing on various biological networks shows that performance enhancement of our approach over existing state-of-the-art approaches varies between 6x and 53x. © 2014 IEEE.

  15. Structural Quality of Service in Large-Scale Networks

    DEFF Research Database (Denmark)

    Pedersen, Jens Myrup

    , telephony and data. To meet the requirements of the different applications, and to handle the increased vulnerability to failures, the ability to design robust networks providing good Quality of Service is crucial. However, most planning of large-scale networks today is ad-hoc based, leading to highly...... complex networks lacking predictability and global structural properties. The thesis applies the concept of Structural Quality of Service to formulate desirable global properties, and it shows how regular graph structures can be used to obtain such properties.......Digitalization has created the base for co-existence and convergence in communications, leading to an increasing use of multi service networks. This is for example seen in the Fiber To The Home implementations, where a single fiber is used for virtually all means of communication, including TV...

  16. Multirelational organization of large-scale social networks in an online world.

    Science.gov (United States)

    Szell, Michael; Lambiotte, Renaud; Thurner, Stefan

    2010-08-03

    The capacity to collect fingerprints of individuals in online media has revolutionized the way researchers explore human society. Social systems can be seen as a nonlinear superposition of a multitude of complex social networks, where nodes represent individuals and links capture a variety of different social relations. Much emphasis has been put on the network topology of social interactions, however, the multidimensional nature of these interactions has largely been ignored, mostly because of lack of data. Here, for the first time, we analyze a complete, multirelational, large social network of a society consisting of the 300,000 odd players of a massive multiplayer online game. We extract networks of six different types of one-to-one interactions between the players. Three of them carry a positive connotation (friendship, communication, trade), three a negative (enmity, armed aggression, punishment). We first analyze these types of networks as separate entities and find that negative interactions differ from positive interactions by their lower reciprocity, weaker clustering, and fatter-tail degree distribution. We then explore how the interdependence of different network types determines the organization of the social system. In particular, we study correlations and overlap between different types of links and demonstrate the tendency of individuals to play different roles in different networks. As a demonstration of the power of the approach, we present the first empirical large-scale verification of the long-standing structural balance theory, by focusing on the specific multiplex network of friendship and enmity relations.

  17. Physical limits of feedback noise-suppression in biological networks

    International Nuclear Information System (INIS)

    Zhang, Jiajun; Yuan, Zhanjiang; Zhou, Tianshou

    2009-01-01

    Feedback is a ubiquitous control mechanism of biological networks, and has also been identified in a variety of regulatory systems and organisms. It has been shown that, for a given gain and with negligible intrinsic noise, negative feedback impairs noise buffering whereas positive feedback enhances noise buffering. We further investigate the influence of negative and positive feedback on noise in output signals by considering both intrinsic and extrinsic noise as well as operator noise. We find that, while maintaining the system sensitivity, either there exists a minimum of the output noise intensity corresponding to a biologically feasible feedback strength, or the output noise intensity is a monotonic function of feedback strength bounded by both biological and dynamical constraints. In both cases, feedback noise-suppression is physically limited. In other words, noise suppressed by negative or positive feedback cannot be reduced without limitation even in the case of slow transcription

  18. Double network bacterial cellulose hydrogel to build a biology-device interface

    Science.gov (United States)

    Shi, Zhijun; Li, Ying; Chen, Xiuli; Han, Hongwei; Yang, Guang

    2013-12-01

    Establishing a biology-device interface might enable the interaction between microelectronics and biotechnology. In this study, electroactive hydrogels have been produced using bacterial cellulose (BC) and conducting polymer (CP) deposited on the BC hydrogel surface to cover the BC fibers. The structures of these composites thus have double networks, one of which is a layer of electroactive hydrogels combined with BC and CP. The electroconductivity provides the composites with capabilities for voltage and current response, and the BC hydrogel layer provides good biocompatibility, biodegradability, bioadhesion and mass transport properties. Such a system might allow selective biological functions such as molecular recognition and specific catalysis and also for probing the detailed genetic and molecular mechanisms of life. A BC-CP composite hydrogel could then lead to a biology-device interface. Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) are used here to study the composite hydrogels' electroactive property. BC-PAni and BC-PPy respond to voltage changes. This provides a mechanism to amplify electrochemical signals for analysis or detection. BC hydrogels were found to be able to support the growth, spreading and migration of human normal skin fibroblasts without causing any cytotoxic effect on the cells in the cell culture. These double network BC-CP hydrogels are biphasic Janus hydrogels which integrate electroactivity with biocompatibility, and might provide a biology-device interface to produce implantable devices for personalized and regenerative medicine.

  19. A comparative analysis of the statistical properties of large mobile phone calling networks.

    Science.gov (United States)

    Li, Ming-Xia; Jiang, Zhi-Qiang; Xie, Wen-Jie; Miccichè, Salvatore; Tumminello, Michele; Zhou, Wei-Xing; Mantegna, Rosario N

    2014-05-30

    Mobile phone calling is one of the most widely used communication methods in modern society. The records of calls among mobile phone users provide us a valuable proxy for the understanding of human communication patterns embedded in social networks. Mobile phone users call each other forming a directed calling network. If only reciprocal calls are considered, we obtain an undirected mutual calling network. The preferential communication behavior between two connected users can be statistically tested and it results in two Bonferroni networks with statistically validated edges. We perform a comparative analysis of the statistical properties of these four networks, which are constructed from the calling records of more than nine million individuals in Shanghai over a period of 110 days. We find that these networks share many common structural properties and also exhibit idiosyncratic features when compared with previously studied large mobile calling networks. The empirical findings provide us an intriguing picture of a representative large social network that might shed new lights on the modelling of large social networks.

  20. An attempt to understand glioma stem cell biology through centrality analysis of a protein interaction network.

    Science.gov (United States)

    Mallik, Mrinmay Kumar

    2018-02-07

    Biological networks can be analyzed using "Centrality Analysis" to identify the more influential nodes and interactions in the network. This study was undertaken to create and visualize a biological network comprising of protein-protein interactions (PPIs) amongst proteins which are preferentially over-expressed in glioma cancer stem cell component (GCSC) of glioblastomas as compared to the glioma non-stem cancer cell (GNSC) component and then to analyze this network through centrality analyses (CA) in order to identify the essential proteins in this network and their interactions. In addition, this study proposes a new centrality analysis method pertaining exclusively to transcription factors (TFs) and interactions amongst them. Moreover the relevant molecular functions, biological processes and biochemical pathways amongst these proteins were sought through enrichment analysis. A protein interaction network was created using a list of proteins which have been shown to be preferentially expressed or over-expressed in GCSCs isolated from glioblastomas as compared to the GNSCs. This list comprising of 38 proteins, created using manual literature mining, was submitted to the Reactome FIViz tool, a web based application integrated into Cytoscape, an open source software platform for visualizing and analyzing molecular interaction networks and biological pathways to produce the network. This network was subjected to centrality analyses utilizing ranked lists of six centrality measures using the FIViz application and (for the first time) a dedicated centrality analysis plug-in ; CytoNCA. The interactions exclusively amongst the transcription factors were nalyzed through a newly proposed centrality analysis method called "Gene Expression Associated Degree Centrality Analysis (GEADCA)". Enrichment analysis was performed using the "network function analysis" tool on Reactome. The CA was able to identify a small set of proteins with consistently high centrality ranks that

  1. Integrated Network Analysis and Effective Tools in Plant Systems Biology

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2014-11-01

    Full Text Available One of the ultimate goals in plant systems biology is to elucidate the genotype-phenotype relationship in plant cellular systems. Integrated network analysis that combines omics data with mathematical models has received particular attention. Here we focus on the latest cutting-edge computational advances that facilitate their combination. We highlight (1 network visualization tools, (2 pathway analyses, (3 genome-scale metabolic reconstruction, and (4 the integration of high-throughput experimental data and mathematical models. Multi-omics data that contain the genome, transcriptome, proteome, and metabolome and mathematical models are expected to integrate and expand our knowledge of complex plant metabolisms.

  2. A Gossip-based Churn Estimator for Large Dynamic Networks

    NARCIS (Netherlands)

    Giuffrida, C.; Ortolani, S.

    2010-01-01

    Gossip-based aggregation is an emerging paradigm to perform distributed computations and measurements in a large-scale setting. In this paper we explore the possibility of using gossip-based aggregation to estimate churn in arbitrarily large networks. To this end, we introduce a new model to compute

  3. Parallel clustering algorithm for large-scale biological data sets.

    Science.gov (United States)

    Wang, Minchao; Zhang, Wu; Ding, Wang; Dai, Dongbo; Zhang, Huiran; Xie, Hao; Chen, Luonan; Guo, Yike; Xie, Jiang

    2014-01-01

    Recent explosion of biological data brings a great challenge for the traditional clustering algorithms. With increasing scale of data sets, much larger memory and longer runtime are required for the cluster identification problems. The affinity propagation algorithm outperforms many other classical clustering algorithms and is widely applied into the biological researches. However, the time and space complexity become a great bottleneck when handling the large-scale data sets. Moreover, the similarity matrix, whose constructing procedure takes long runtime, is required before running the affinity propagation algorithm, since the algorithm clusters data sets based on the similarities between data pairs. Two types of parallel architectures are proposed in this paper to accelerate the similarity matrix constructing procedure and the affinity propagation algorithm. The memory-shared architecture is used to construct the similarity matrix, and the distributed system is taken for the affinity propagation algorithm, because of its large memory size and great computing capacity. An appropriate way of data partition and reduction is designed in our method, in order to minimize the global communication cost among processes. A speedup of 100 is gained with 128 cores. The runtime is reduced from serval hours to a few seconds, which indicates that parallel algorithm is capable of handling large-scale data sets effectively. The parallel affinity propagation also achieves a good performance when clustering large-scale gene data (microarray) and detecting families in large protein superfamilies.

  4. MORE: mixed optimization for reverse engineering--an application to modeling biological networks response via sparse systems of nonlinear differential equations.

    Science.gov (United States)

    Sambo, Francesco; de Oca, Marco A Montes; Di Camillo, Barbara; Toffolo, Gianna; Stützle, Thomas

    2012-01-01

    Reverse engineering is the problem of inferring the structure of a network of interactions between biological variables from a set of observations. In this paper, we propose an optimization algorithm, called MORE, for the reverse engineering of biological networks from time series data. The model inferred by MORE is a sparse system of nonlinear differential equations, complex enough to realistically describe the dynamics of a biological system. MORE tackles separately the discrete component of the problem, the determination of the biological network topology, and the continuous component of the problem, the strength of the interactions. This approach allows us both to enforce system sparsity, by globally constraining the number of edges, and to integrate a priori information about the structure of the underlying interaction network. Experimental results on simulated and real-world networks show that the mixed discrete/continuous optimization approach of MORE significantly outperforms standard continuous optimization and that MORE is competitive with the state of the art in terms of accuracy of the inferred networks.

  5. Complex modular structure of large-scale brain networks

    Science.gov (United States)

    Valencia, M.; Pastor, M. A.; Fernández-Seara, M. A.; Artieda, J.; Martinerie, J.; Chavez, M.

    2009-06-01

    Modular structure is ubiquitous among real-world networks from related proteins to social groups. Here we analyze the modular organization of brain networks at a large scale (voxel level) extracted from functional magnetic resonance imaging signals. By using a random-walk-based method, we unveil the modularity of brain webs and show modules with a spatial distribution that matches anatomical structures with functional significance. The functional role of each node in the network is studied by analyzing its patterns of inter- and intramodular connections. Results suggest that the modular architecture constitutes the structural basis for the coexistence of functional integration of distant and specialized brain areas during normal brain activities at rest.

  6. Large-Scale Recurrent Neural Network Based Modelling of Gene Regulatory Network Using Cuckoo Search-Flower Pollination Algorithm.

    Science.gov (United States)

    Mandal, Sudip; Khan, Abhinandan; Saha, Goutam; Pal, Rajat K

    2016-01-01

    The accurate prediction of genetic networks using computational tools is one of the greatest challenges in the postgenomic era. Recurrent Neural Network is one of the most popular but simple approaches to model the network dynamics from time-series microarray data. To date, it has been successfully applied to computationally derive small-scale artificial and real-world genetic networks with high accuracy. However, they underperformed for large-scale genetic networks. Here, a new methodology has been proposed where a hybrid Cuckoo Search-Flower Pollination Algorithm has been implemented with Recurrent Neural Network. Cuckoo Search is used to search the best combination of regulators. Moreover, Flower Pollination Algorithm is applied to optimize the model parameters of the Recurrent Neural Network formalism. Initially, the proposed method is tested on a benchmark large-scale artificial network for both noiseless and noisy data. The results obtained show that the proposed methodology is capable of increasing the inference of correct regulations and decreasing false regulations to a high degree. Secondly, the proposed methodology has been validated against the real-world dataset of the DNA SOS repair network of Escherichia coli. However, the proposed method sacrifices computational time complexity in both cases due to the hybrid optimization process.

  7. Mathematical Analysis of a PDE System for Biological Network Formation

    KAUST Repository

    Haskovec, Jan

    2015-02-04

    Motivated by recent physics papers describing rules for natural network formation, we study an elliptic-parabolic system of partial differential equations proposed by Hu and Cai [13, 15]. The model describes the pressure field thanks to Darcy\\'s type equation and the dynamics of the conductance network under pressure force effects with a diffusion rate D >= 0 representing randomness in the material structure. We prove the existence of global weak solutions and of local mild solutions and study their long term behavior. It turns out that, by energy dissipation, steady states play a central role to understand the network formation capacity of the system. We show that for a large diffusion coefficient D, the zero steady state is stable, while network formation occurs for small values of D due to the instability of the zero steady state, and the borderline case D = 0 exhibits a large class of dynamically stable (in the linearized sense) steady states.

  8. Integrating external biological knowledge in the construction of regulatory networks from time-series expression data

    Directory of Open Access Journals (Sweden)

    Lo Kenneth

    2012-08-01

    Full Text Available Abstract Background Inference about regulatory networks from high-throughput genomics data is of great interest in systems biology. We present a Bayesian approach to infer gene regulatory networks from time series expression data by integrating various types of biological knowledge. Results We formulate network construction as a series of variable selection problems and use linear regression to model the data. Our method summarizes additional data sources with an informative prior probability distribution over candidate regression models. We extend the Bayesian model averaging (BMA variable selection method to select regulators in the regression framework. We summarize the external biological knowledge by an informative prior probability distribution over the candidate regression models. Conclusions We demonstrate our method on simulated data and a set of time-series microarray experiments measuring the effect of a drug perturbation on gene expression levels, and show that it outperforms leading regression-based methods in the literature.

  9. Fast network centrality analysis using GPUs

    Directory of Open Access Journals (Sweden)

    Shi Zhiao

    2011-05-01

    Full Text Available Abstract Background With the exploding volume of data generated by continuously evolving high-throughput technologies, biological network analysis problems are growing larger in scale and craving for more computational power. General Purpose computation on Graphics Processing Units (GPGPU provides a cost-effective technology for the study of large-scale biological networks. Designing algorithms that maximize data parallelism is the key in leveraging the power of GPUs. Results We proposed an efficient data parallel formulation of the All-Pairs Shortest Path problem, which is the key component for shortest path-based centrality computation. A betweenness centrality algorithm built upon this formulation was developed and benchmarked against the most recent GPU-based algorithm. Speedup between 11 to 19% was observed in various simulated scale-free networks. We further designed three algorithms based on this core component to compute closeness centrality, eccentricity centrality and stress centrality. To make all these algorithms available to the research community, we developed a software package gpu-fan (GPU-based Fast Analysis of Networks for CUDA enabled GPUs. Speedup of 10-50× compared with CPU implementations was observed for simulated scale-free networks and real world biological networks. Conclusions gpu-fan provides a significant performance improvement for centrality computation in large-scale networks. Source code is available under the GNU Public License (GPL at http://bioinfo.vanderbilt.edu/gpu-fan/.

  10. Networking for large-scale science: infrastructure, provisioning, transport and application mapping

    International Nuclear Information System (INIS)

    Rao, Nageswara S; Carter, Steven M; Wu Qishi; Wing, William R; Zhu Mengxia; Mezzacappa, Anthony; Veeraraghavan, Malathi; Blondin, John M

    2005-01-01

    Large-scale science computations and experiments require unprecedented network capabilities in the form of large bandwidth and dynamically stable connections to support data transfers, interactive visualizations, and monitoring and steering operations. A number of component technologies dealing with the infrastructure, provisioning, transport and application mappings must be developed and/or optimized to achieve these capabilities. We present a brief account of the following technologies that contribute toward achieving these network capabilities: (a) DOE UltraScienceNet and NSF CHEETAH network testbeds that provide on-demand and scheduled dedicated network connections; (b) experimental results on transport protocols that achieve close to 100% utilization on dedicated 1Gbps wide-area channels; (c) a scheme for optimally mapping a visualization pipeline onto a network to minimize the end-to-end delays; and (d) interconnect configuration and protocols that provides multiple Gbps flows from Cray X1 to external hosts

  11. Networking for large-scale science: infrastructure, provisioning, transport and application mapping

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Nageswara S [Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Carter, Steven M [Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Wu Qishi [Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Wing, William R [Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Zhu Mengxia [Department of Computer Science, Louisiana State University, Baton Rouge, LA 70803 (United States); Mezzacappa, Anthony [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Veeraraghavan, Malathi [Department of Computer Science, University of Virginia, Charlottesville, VA 22904 (United States); Blondin, John M [Department of Physics, North Carolina State University, Raleigh, NC 27695 (United States)

    2005-01-01

    Large-scale science computations and experiments require unprecedented network capabilities in the form of large bandwidth and dynamically stable connections to support data transfers, interactive visualizations, and monitoring and steering operations. A number of component technologies dealing with the infrastructure, provisioning, transport and application mappings must be developed and/or optimized to achieve these capabilities. We present a brief account of the following technologies that contribute toward achieving these network capabilities: (a) DOE UltraScienceNet and NSF CHEETAH network testbeds that provide on-demand and scheduled dedicated network connections; (b) experimental results on transport protocols that achieve close to 100% utilization on dedicated 1Gbps wide-area channels; (c) a scheme for optimally mapping a visualization pipeline onto a network to minimize the end-to-end delays; and (d) interconnect configuration and protocols that provides multiple Gbps flows from Cray X1 to external hosts.

  12. S100A4 and its role in metastasis – computational integration of data on biological networks.

    Science.gov (United States)

    Buetti-Dinh, Antoine; Pivkin, Igor V; Friedman, Ran

    2015-08-01

    Characterising signal transduction networks is fundamental to our understanding of biology. However, redundancy and different types of feedback mechanisms make it difficult to understand how variations of the network components contribute to a biological process. In silico modelling of signalling interactions therefore becomes increasingly useful for the development of successful therapeutic approaches. Unfortunately, quantitative information cannot be obtained for all of the proteins or complexes that comprise the network, which limits the usability of computational models. We developed a flexible computational framework for the analysis of biological signalling networks. We demonstrate our approach by studying the mechanism of metastasis promotion by the S100A4 protein, and suggest therapeutic strategies. The advantage of the proposed method is that only limited information (interaction type between species) is required to set up a steady-state network model. This permits a straightforward integration of experimental information where the lack of details are compensated by efficient sampling of the parameter space. We investigated regulatory properties of the S100A4 network and the role of different key components. The results show that S100A4 enhances the activity of matrix metalloproteinases (MMPs), causing higher cell dissociation. Moreover, it leads to an increased stability of the pathological state. Thus, avoiding metastasis in S100A4-expressing tumours requires multiple target inhibition. Moreover, the analysis could explain the previous failure of MMP inhibitors in clinical trials. Finally, our method is applicable to a wide range of biological questions that can be represented as directional networks.

  13. Reverse engineering biological networks :applications in immune responses to bio-toxins.

    Energy Technology Data Exchange (ETDEWEB)

    Martino, Anthony A.; Sinclair, Michael B.; Davidson, George S.; Haaland, David Michael; Timlin, Jerilyn Ann; Thomas, Edward Victor; Slepoy, Alexander; Zhang, Zhaoduo; May, Elebeoba Eni; Martin, Shawn Bryan; Faulon, Jean-Loup Michel

    2005-12-01

    Our aim is to determine the network of events, or the regulatory network, that defines an immune response to a bio-toxin. As a model system, we are studying T cell regulatory network triggered through tyrosine kinase receptor activation using a combination of pathway stimulation and time-series microarray experiments. Our approach is composed of five steps (1) microarray experiments and data error analysis, (2) data clustering, (3) data smoothing and discretization, (4) network reverse engineering, and (5) network dynamics analysis and fingerprint identification. The technological outcome of this study is a suite of experimental protocols and computational tools that reverse engineer regulatory networks provided gene expression data. The practical biological outcome of this work is an immune response fingerprint in terms of gene expression levels. Inferring regulatory networks from microarray data is a new field of investigation that is no more than five years old. To the best of our knowledge, this work is the first attempt that integrates experiments, error analyses, data clustering, inference, and network analysis to solve a practical problem. Our systematic approach of counting, enumeration, and sampling networks matching experimental data is new to the field of network reverse engineering. The resulting mathematical analyses and computational tools lead to new results on their own and should be useful to others who analyze and infer networks.

  14. FMFinder: A Functional Module Detector for PPI Networks

    Directory of Open Access Journals (Sweden)

    M. Modi

    2017-10-01

    Full Text Available Bioinformatics is an integrated area of data mining, statistics and computational biology. Protein-Protein Interaction (PPI network is the most important biological process in living beings. In this network a protein module interacts with another module and so on, forming a large network of proteins. The same set of proteins which takes part in the organic courses of biological actions is detected through the Function Module Detection method. Clustering process when applied in PPI networks is made of proteins which are part of a larger communication network. As a result of this, we can define the limits for module detection as well as clarify the construction of a PPI network. For understating the bio-mechanism of various living beings, a detailed study of FMFinder detection by clustering process is called for.

  15. SWIM: a computational tool to unveiling crucial nodes in complex biological networks.

    Science.gov (United States)

    Paci, Paola; Colombo, Teresa; Fiscon, Giulia; Gurtner, Aymone; Pavesi, Giulio; Farina, Lorenzo

    2017-03-20

    SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called "fight-club hubs", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called "switch genes", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance. Here, we applied SWIM to a large panel of cancer datasets from The Cancer Genome Atlas, in order to highlight switch genes that could be critically associated with the drastic changes in the physiological state of cells or tissues induced by the cancer development. We discovered that switch genes are found in all cancers we studied and they encompass protein coding genes and non-coding RNAs, recovering many known key cancer players but also many new potential biomarkers not yet characterized in cancer context. Furthermore, SWIM is amenable to detect switch genes in different organisms and cell conditions, with the potential to uncover important players in biologically relevant scenarios, including but not limited to human cancer.

  16. FUSE: a profit maximization approach for functional summarization of biological networks.

    Science.gov (United States)

    Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes; Yu, Hanry

    2012-03-21

    The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI) using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator) that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL) principle to maximize information gain of the summary graph while satisfying the level of detail constraint. We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

  17. Large scale network management. Condition indicators for network stations, high voltage power conductions and cables

    International Nuclear Information System (INIS)

    Eggen, Arnt Ove; Rolfseng, Lars; Langdal, Bjoern Inge

    2006-02-01

    In the Strategic Institute Programme (SIP) 'Electricity Business enters e-business (eBee)' SINTEF Energy research has developed competency that can help the energy business employ ICT systems and computer technology in an improved way. Large scale network management is now a reality, and it is characterized by large entities with increasing demands on efficiency and quality. These are goals that can only be reached by using ICT systems and computer technology in a more clever way than what is the case today. At the same time it is important that knowledge held by experienced co-workers is consulted when formal rules for evaluations and decisions in ICT systems are developed. In this project an analytical concept for evaluation of networks based information in different ICT systems has been developed. The method estimating the indicators to describe different conditions in a network is general, and indicators can be made to fit different levels of decision and network levels, for example network station, transformer circuit, distribution network and regional network. Moreover, the indicators can contain information about technical aspects, economy and HSE. An indicator consists of an indicator name, an indicator value, and an indicator colour based on a traffic-light analogy to indicate a condition or a quality for the indicator. Values on one or more indicators give an impression of important conditions in the network, and make up the basis for knowing where more detailed evaluations have to be conducted before a final decision on for example maintenance or renewal is made. A prototype has been developed for testing the new method. The prototype has been developed in Excel, and especially designed for analysing transformer circuits in a distribution network. However, the method is a general one, and well suited for implementation in a commercial computer system (ml)

  18. Practical characterization of large networks using neighborhood information

    KAUST Repository

    Wang, Pinghui; Zhao, Junzhou; Ribeiro, Bruno; Lui, John C. S.; Towsley, Don; Guan, Xiaohong

    2018-01-01

    querying a node also reveals partial structural information about its neighbors. Our methods are optimized for NoSQL graph databases (if the database can be accessed directly), or utilize Web APIs available on most major large networks for graph sampling

  19. Information-Theoretic Inference of Large Transcriptional Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Meyer Patrick

    2007-01-01

    Full Text Available The paper presents MRNET, an original method for inferring genetic networks from microarray data. The method is based on maximum relevance/minimum redundancy (MRMR, an effective information-theoretic technique for feature selection in supervised learning. The MRMR principle consists in selecting among the least redundant variables the ones that have the highest mutual information with the target. MRNET extends this feature selection principle to networks in order to infer gene-dependence relationships from microarray data. The paper assesses MRNET by benchmarking it against RELNET, CLR, and ARACNE, three state-of-the-art information-theoretic methods for large (up to several thousands of genes network inference. Experimental results on thirty synthetically generated microarray datasets show that MRNET is competitive with these methods.

  20. Information-Theoretic Inference of Large Transcriptional Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Patrick E. Meyer

    2007-06-01

    Full Text Available The paper presents MRNET, an original method for inferring genetic networks from microarray data. The method is based on maximum relevance/minimum redundancy (MRMR, an effective information-theoretic technique for feature selection in supervised learning. The MRMR principle consists in selecting among the least redundant variables the ones that have the highest mutual information with the target. MRNET extends this feature selection principle to networks in order to infer gene-dependence relationships from microarray data. The paper assesses MRNET by benchmarking it against RELNET, CLR, and ARACNE, three state-of-the-art information-theoretic methods for large (up to several thousands of genes network inference. Experimental results on thirty synthetically generated microarray datasets show that MRNET is competitive with these methods.

  1. Enhancement of COPD biological networks using a web-based collaboration interface [v2; ref status: indexed, http://f1000r.es/5ew

    Directory of Open Access Journals (Sweden)

    The sbv IMPROVER project team (in alphabetical order

    2015-05-01

    Full Text Available The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website (https://bionet.sbvimprover.com/ and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD

  2. Network motif frequency vectors reveal evolving metabolic network organisation.

    Science.gov (United States)

    Pearcy, Nicole; Crofts, Jonathan J; Chuzhanova, Nadia

    2015-01-01

    At the systems level many organisms of interest may be described by their patterns of interaction, and as such, are perhaps best characterised via network or graph models. Metabolic networks, in particular, are fundamental to the proper functioning of many important biological processes, and thus, have been widely studied over the past decade or so. Such investigations have revealed a number of shared topological features, such as a short characteristic path-length, large clustering coefficient and hierarchical modular structure. However, the extent to which evolutionary and functional properties of metabolism manifest via this underlying network architecture remains unclear. In this paper, we employ a novel graph embedding technique, based upon low-order network motifs, to compare metabolic network structure for 383 bacterial species categorised according to a number of biological features. In particular, we introduce a new global significance score which enables us to quantify important evolutionary relationships that exist between organisms and their physical environments. Using this new approach, we demonstrate a number of significant correlations between environmental factors, such as growth conditions and habitat variability, and network motif structure, providing evidence that organism adaptability leads to increased complexities in the resultant metabolic networks.

  3. Risk-based optimization of pipe inspections in large underground networks with imprecise information

    International Nuclear Information System (INIS)

    Mancuso, A.; Compare, M.; Salo, A.; Zio, E.; Laakso, T.

    2016-01-01

    In this paper, we present a novel risk-based methodology for optimizing the inspections of large underground infrastructure networks in the presence of incomplete information about the network features and parameters. The methodology employs Multi Attribute Value Theory to assess the risk of each pipe in the network, whereafter the optimal inspection campaign is built with Portfolio Decision Analysis (PDA). Specifically, Robust Portfolio Modeling (RPM) is employed to identify Pareto-optimal portfolios of pipe inspections. The proposed methodology is illustrated by reporting a real case study on the large-scale maintenance optimization of the sewerage network in Espoo, Finland. - Highlights: • Risk-based approach to optimize pipe inspections on large underground networks. • Reasonable computational effort to select efficient inspection portfolios. • Possibility to accommodate imprecise expert information. • Feasibility of the approach shown by Espoo water system case study.

  4. Research on Fault Prediction of Distribution Network Based on Large Data

    Directory of Open Access Journals (Sweden)

    Jinglong Zhou

    2017-01-01

    Full Text Available With the continuous development of information technology and the improvement of distribution automation level. Especially, the amount of on-line monitoring and statistical data is increasing, and large data is used data distribution system, describes the technology to collect, data analysis and data processing of the data distribution system. The artificial neural network mining algorithm and the large data are researched in the fault diagnosis and prediction of the distribution network.

  5. A Matrix-Based Proactive Data Relay Algorithm for Large Distributed Sensor Networks.

    Science.gov (United States)

    Xu, Yang; Hu, Xuemei; Hu, Haixiao; Liu, Ming

    2016-08-16

    In large-scale distributed sensor networks, sensed data is required to be relayed around the network so that one or few sensors can gather adequate relative data to produce high quality information for decision-making. In regards to very high energy-constraint sensor nodes, data transmission should be extremely economical. However, traditional data delivery protocols are potentially inefficient relaying unpredictable sensor readings for data fusion in large distributed networks for either overwhelming query transmissions or unnecessary data coverage. By building sensors' local model from their previously transmitted data in three matrixes, we have developed a novel energy-saving data relay algorithm, which allows sensors to proactively make broadcast decisions by using a neat matrix computation to provide balance between transmission and energy-saving. In addition, we designed a heuristic maintenance algorithm to efficiently update these three matrices. This can easily be deployed to large-scale mobile networks in which decisions of sensors are based on their local matrix models no matter how large the network is, and the local models of these sensors are updated constantly. Compared with some traditional approaches based on our simulations, the efficiency of this approach is manifested in uncertain environment. The results show that our approach is scalable and can effectively balance aggregating data with minimizing energy consumption.

  6. Unified Tractable Model for Large-Scale Networks Using Stochastic Geometry: Analysis and Design

    KAUST Repository

    Afify, Laila H.

    2016-12-01

    The ever-growing demands for wireless technologies necessitate the evolution of next generation wireless networks that fulfill the diverse wireless users requirements. However, upscaling existing wireless networks implies upscaling an intrinsic component in the wireless domain; the aggregate network interference. Being the main performance limiting factor, it becomes crucial to develop a rigorous analytical framework to accurately characterize the out-of-cell interference, to reap the benefits of emerging networks. Due to the different network setups and key performance indicators, it is essential to conduct a comprehensive study that unifies the various network configurations together with the different tangible performance metrics. In that regard, the focus of this thesis is to present a unified mathematical paradigm, based on Stochastic Geometry, for large-scale networks with different antenna/network configurations. By exploiting such a unified study, we propose an efficient automated network design strategy to satisfy the desired network objectives. First, this thesis studies the exact aggregate network interference characterization, by accounting for each of the interferers signals in the large-scale network. Second, we show that the information about the interferers symbols can be approximated via the Gaussian signaling approach. The developed mathematical model presents twofold analysis unification for uplink and downlink cellular networks literature. It aligns the tangible decoding error probability analysis with the abstract outage probability and ergodic rate analysis. Furthermore, it unifies the analysis for different antenna configurations, i.e., various multiple-input multiple-output (MIMO) systems. Accordingly, we propose a novel reliable network design strategy that is capable of appropriately adjusting the network parameters to meet desired design criteria. In addition, we discuss the diversity-multiplexing tradeoffs imposed by differently favored

  7. Development of large-scale functional brain networks in children.

    Directory of Open Access Journals (Sweden)

    Kaustubh Supekar

    2009-07-01

    Full Text Available The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y and 22 young-adults (ages 19-22 y. Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

  8. Development of large-scale functional brain networks in children.

    Science.gov (United States)

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-07-01

    The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

  9. Hierarchical and Matrix Structures in a Large Organizational Email Network: Visualization and Modeling Approaches

    OpenAIRE

    Sims, Benjamin H.; Sinitsyn, Nikolai; Eidenbenz, Stephan J.

    2014-01-01

    This paper presents findings from a study of the email network of a large scientific research organization, focusing on methods for visualizing and modeling organizational hierarchies within large, complex network datasets. In the first part of the paper, we find that visualization and interpretation of complex organizational network data is facilitated by integration of network data with information on formal organizational divisions and levels. By aggregating and visualizing email traffic b...

  10. The key network communication technology in large radiation image cooperative process system

    International Nuclear Information System (INIS)

    Li Zheng; Kang Kejun; Gao Wenhuan; Wang Jingjin

    1998-01-01

    Large container inspection system (LCIS) based on radiation imaging technology is a powerful tool for the customs to check the contents inside a large container without opening it. An image distributed network system is composed of operation manager station, image acquisition station, environment control station, inspection processing station, check-in station, check-out station, database station by using advanced network technology. Mass data, such as container image data, container general information, manifest scanning data, commands and status, must be on-line transferred between different stations. Advanced network communication technology is presented

  11. Application and study of advanced network technology in large container inspection system

    International Nuclear Information System (INIS)

    Li Zheng; Kang Kejun; Gao Wenhuan; Wang Jingjin

    1996-01-01

    Large Container Inspection System (LCIS) based on radiation imaging technology is a powerful tool for the customs to check the contents inside a large container without opening it. An image distributed network system is composed of center manager station, image acquisition station, environment control station, inspection processing station, check-in station, check-out station, database station by using advanced network technology. Mass data, such as container image data, container general information, manifest scanning data, commands and status, must be on-line transferred between different stations. Advanced network technology and software programming technique are presented

  12. Large Amplitude Oscillatory Extension of Soft Polymeric Networks

    DEFF Research Database (Denmark)

    Bejenariu, Anca Gabriela; Rasmussen, Henrik K.; Skov, Anne Ladegaard

    2010-01-01

    sing a filament stretching rheometer (FSR) surrounded by a thermostatic chamber and equipped with a micrometric laser it is possible to measure large amplitude oscillatory elongation (LAOE) on elastomeric based networks with no base flow as in the LAOE method for polymer melts. Poly(dimethylsilox...

  13. Enhancement of large fluctuations to extinction in adaptive networks

    Science.gov (United States)

    Hindes, Jason; Schwartz, Ira B.; Shaw, Leah B.

    2018-01-01

    During an epidemic, individual nodes in a network may adapt their connections to reduce the chance of infection. A common form of adaption is avoidance rewiring, where a noninfected node breaks a connection to an infected neighbor and forms a new connection to another noninfected node. Here we explore the effects of such adaptivity on stochastic fluctuations in the susceptible-infected-susceptible model, focusing on the largest fluctuations that result in extinction of infection. Using techniques from large-deviation theory, combined with a measurement of heterogeneity in the susceptible degree distribution at the endemic state, we are able to predict and analyze large fluctuations and extinction in adaptive networks. We find that in the limit of small rewiring there is a sharp exponential reduction in mean extinction times compared to the case of zero adaption. Furthermore, we find an exponential enhancement in the probability of large fluctuations with increased rewiring rate, even when holding the average number of infected nodes constant.

  14. Biologically plausible learning in neural networks: a lesson from bacterial chemotaxis.

    Science.gov (United States)

    Shimansky, Yury P

    2009-12-01

    Learning processes in the brain are usually associated with plastic changes made to optimize the strength of connections between neurons. Although many details related to biophysical mechanisms of synaptic plasticity have been discovered, it is unclear how the concurrent performance of adaptive modifications in a huge number of spatial locations is organized to minimize a given objective function. Since direct experimental observation of even a relatively small subset of such changes is not feasible, computational modeling is an indispensable investigation tool for solving this problem. However, the conventional method of error back-propagation (EBP) employed for optimizing synaptic weights in artificial neural networks is not biologically plausible. This study based on computational experiments demonstrated that such optimization can be performed rather efficiently using the same general method that bacteria employ for moving closer to an attractant or away from a repellent. With regard to neural network optimization, this method consists of regulating the probability of an abrupt change in the direction of synaptic weight modification according to the temporal gradient of the objective function. Neural networks utilizing this method (regulation of modification probability, RMP) can be viewed as analogous to swimming in the multidimensional space of their parameters in the flow of biochemical agents carrying information about the optimality criterion. The efficiency of RMP is comparable to that of EBP, while RMP has several important advantages. Since the biological plausibility of RMP is beyond a reasonable doubt, the RMP concept provides a constructive framework for the experimental analysis of learning in natural neural networks.

  15. A multilevel layout algorithm for visualizing physical and genetic interaction networks, with emphasis on their modular organization.

    Science.gov (United States)

    Tuikkala, Johannes; Vähämaa, Heidi; Salmela, Pekka; Nevalainen, Olli S; Aittokallio, Tero

    2012-03-26

    Graph drawing is an integral part of many systems biology studies, enabling visual exploration and mining of large-scale biological networks. While a number of layout algorithms are available in popular network analysis platforms, such as Cytoscape, it remains poorly understood how well their solutions reflect the underlying biological processes that give rise to the network connectivity structure. Moreover, visualizations obtained using conventional layout algorithms, such as those based on the force-directed drawing approach, may become uninformative when applied to larger networks with dense or clustered connectivity structure. We implemented a modified layout plug-in, named Multilevel Layout, which applies the conventional layout algorithms within a multilevel optimization framework to better capture the hierarchical modularity of many biological networks. Using a wide variety of real life biological networks, we carried out a systematic evaluation of the method in comparison with other layout algorithms in Cytoscape. The multilevel approach provided both biologically relevant and visually pleasant layout solutions in most network types, hence complementing the layout options available in Cytoscape. In particular, it could improve drawing of large-scale networks of yeast genetic interactions and human physical interactions. In more general terms, the biological evaluation framework developed here enables one to assess the layout solutions from any existing or future graph drawing algorithm as well as to optimize their performance for a given network type or structure. By making use of the multilevel modular organization when visualizing biological networks, together with the biological evaluation of the layout solutions, one can generate convenient visualizations for many network biology applications.

  16. A Matrix-Based Proactive Data Relay Algorithm for Large Distributed Sensor Networks

    Directory of Open Access Journals (Sweden)

    Yang Xu

    2016-08-01

    Full Text Available In large-scale distributed sensor networks, sensed data is required to be relayed around the network so that one or few sensors can gather adequate relative data to produce high quality information for decision-making. In regards to very high energy-constraint sensor nodes, data transmission should be extremely economical. However, traditional data delivery protocols are potentially inefficient relaying unpredictable sensor readings for data fusion in large distributed networks for either overwhelming query transmissions or unnecessary data coverage. By building sensors’ local model from their previously transmitted data in three matrixes, we have developed a novel energy-saving data relay algorithm, which allows sensors to proactively make broadcast decisions by using a neat matrix computation to provide balance between transmission and energy-saving. In addition, we designed a heuristic maintenance algorithm to efficiently update these three matrices. This can easily be deployed to large-scale mobile networks in which decisions of sensors are based on their local matrix models no matter how large the network is, and the local models of these sensors are updated constantly. Compared with some traditional approaches based on our simulations, the efficiency of this approach is manifested in uncertain environment. The results show that our approach is scalable and can effectively balance aggregating data with minimizing energy consumption.

  17. Functional Module Analysis for Gene Coexpression Networks with Network Integration.

    Science.gov (United States)

    Zhang, Shuqin; Zhao, Hongyu; Ng, Michael K

    2015-01-01

    Network has been a general tool for studying the complex interactions between different genes, proteins, and other small molecules. Module as a fundamental property of many biological networks has been widely studied and many computational methods have been proposed to identify the modules in an individual network. However, in many cases, a single network is insufficient for module analysis due to the noise in the data or the tuning of parameters when building the biological network. The availability of a large amount of biological networks makes network integration study possible. By integrating such networks, more informative modules for some specific disease can be derived from the networks constructed from different tissues, and consistent factors for different diseases can be inferred. In this paper, we have developed an effective method for module identification from multiple networks under different conditions. The problem is formulated as an optimization model, which combines the module identification in each individual network and alignment of the modules from different networks together. An approximation algorithm based on eigenvector computation is proposed. Our method outperforms the existing methods, especially when the underlying modules in multiple networks are different in simulation studies. We also applied our method to two groups of gene coexpression networks for humans, which include one for three different cancers, and one for three tissues from the morbidly obese patients. We identified 13 modules with three complete subgraphs, and 11 modules with two complete subgraphs, respectively. The modules were validated through Gene Ontology enrichment and KEGG pathway enrichment analysis. We also showed that the main functions of most modules for the corresponding disease have been addressed by other researchers, which may provide the theoretical basis for further studying the modules experimentally.

  18. Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information

    Directory of Open Access Journals (Sweden)

    Lemke Ney

    2009-09-01

    Full Text Available Abstract Background The identification of essential genes is important for the understanding of the minimal requirements for cellular life and for practical purposes, such as drug design. However, the experimental techniques for essential genes discovery are labor-intensive and time-consuming. Considering these experimental constraints, a computational approach capable of accurately predicting essential genes would be of great value. We therefore present here a machine learning-based computational approach relying on network topological features, cellular localization and biological process information for prediction of essential genes. Results We constructed a decision tree-based meta-classifier and trained it on datasets with individual and grouped attributes-network topological features, cellular compartments and biological processes-to generate various predictors of essential genes. We showed that the predictors with better performances are those generated by datasets with integrated attributes. Using the predictor with all attributes, i.e., network topological features, cellular compartments and biological processes, we obtained the best predictor of essential genes that was then used to classify yeast genes with unknown essentiality status. Finally, we generated decision trees by training the J48 algorithm on datasets with all network topological features, cellular localization and biological process information to discover cellular rules for essentiality. We found that the number of protein physical interactions, the nuclear localization of proteins and the number of regulating transcription factors are the most important factors determining gene essentiality. Conclusion We were able to demonstrate that network topological features, cellular localization and biological process information are reliable predictors of essential genes. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing

  19. A framework to find the logic backbone of a biological network.

    Science.gov (United States)

    Maheshwari, Parul; Albert, Réka

    2017-12-06

    Cellular behaviors are governed by interaction networks among biomolecules, for example gene regulatory and signal transduction networks. An often used dynamic modeling framework for these networks, Boolean modeling, can obtain their attractors (which correspond to cell types and behaviors) and their trajectories from an initial state (e.g. a resting state) to the attractors, for example in response to an external signal. The existing methods however do not elucidate the causal relationships between distant nodes in the network. In this work, we propose a simple logic framework, based on categorizing causal relationships as sufficient or necessary, as a complement to Boolean networks. We identify and explore the properties of complex subnetworks that are distillable into a single logic relationship. We also identify cyclic subnetworks that ensure the stabilization of the state of participating nodes regardless of the rest of the network. We identify the logic backbone of biomolecular networks, consisting of external signals, self-sustaining cyclic subnetworks (stable motifs), and output nodes. Furthermore, we use the logic framework to identify crucial nodes whose override can drive the system from one steady state to another. We apply these techniques to two biological networks: the epithelial-to-mesenchymal transition network corresponding to a developmental process exploited in tumor invasion, and the network of abscisic acid induced stomatal closure in plants. We find interesting subnetworks with logical implications in these networks. Using these subgraphs and motifs, we efficiently reduce both networks to succinct backbone structures. The logic representation identifies the causal relationships between distant nodes and subnetworks. This knowledge can form the basis of network control or used in the reverse engineering of networks.

  20. GraphAlignment: Bayesian pairwise alignment of biological networks

    Directory of Open Access Journals (Sweden)

    Kolář Michal

    2012-11-01

    Full Text Available Abstract Background With increased experimental availability and accuracy of bio-molecular networks, tools for their comparative and evolutionary analysis are needed. A key component for such studies is the alignment of networks. Results We introduce the Bioconductor package GraphAlignment for pairwise alignment of bio-molecular networks. The alignment incorporates information both from network vertices and network edges and is based on an explicit evolutionary model, allowing inference of all scoring parameters directly from empirical data. We compare the performance of our algorithm to an alternative algorithm, Græmlin 2.0. On simulated data, GraphAlignment outperforms Græmlin 2.0 in several benchmarks except for computational complexity. When there is little or no noise in the data, GraphAlignment is slower than Græmlin 2.0. It is faster than Græmlin 2.0 when processing noisy data containing spurious vertex associations. Its typical case complexity grows approximately as O(N2.6. On empirical bacterial protein-protein interaction networks (PIN and gene co-expression networks, GraphAlignment outperforms Græmlin 2.0 with respect to coverage and specificity, albeit by a small margin. On large eukaryotic PIN, Græmlin 2.0 outperforms GraphAlignment. Conclusions The GraphAlignment algorithm is robust to spurious vertex associations, correctly resolves paralogs, and shows very good performance in identification of homologous vertices defined by high vertex and/or interaction similarity. The simplicity and generality of GraphAlignment edge scoring makes the algorithm an appropriate choice for global alignment of networks.

  1. Large-scale network dynamics of beta-band oscillations underlie auditory perceptual decision-making

    Directory of Open Access Journals (Sweden)

    Mohsen Alavash

    2017-06-01

    Full Text Available Perceptual decisions vary in the speed at which we make them. Evidence suggests that translating sensory information into perceptual decisions relies on distributed interacting neural populations, with decision speed hinging on power modulations of the neural oscillations. Yet the dependence of perceptual decisions on the large-scale network organization of coupled neural oscillations has remained elusive. We measured magnetoencephalographic signals in human listeners who judged acoustic stimuli composed of carefully titrated clouds of tone sweeps. These stimuli were used in two task contexts, in which the participants judged the overall pitch or direction of the tone sweeps. We traced the large-scale network dynamics of the source-projected neural oscillations on a trial-by-trial basis using power-envelope correlations and graph-theoretical network discovery. In both tasks, faster decisions were predicted by higher segregation and lower integration of coupled beta-band (∼16–28 Hz oscillations. We also uncovered the brain network states that promoted faster decisions in either lower-order auditory or higher-order control brain areas. Specifically, decision speed in judging the tone sweep direction critically relied on the nodal network configurations of anterior temporal, cingulate, and middle frontal cortices. Our findings suggest that global network communication during perceptual decision-making is implemented in the human brain by large-scale couplings between beta-band neural oscillations. The speed at which we make perceptual decisions varies. This translation of sensory information into perceptual decisions hinges on dynamic changes in neural oscillatory activity. However, the large-scale neural-network embodiment supporting perceptual decision-making is unclear. We addressed this question by experimenting two auditory perceptual decision-making situations. Using graph-theoretical network discovery, we traced the large-scale network

  2. Multisector Health Policy Networks in 15 Large US Cities

    Science.gov (United States)

    Leider, J. P.; Carothers, Bobbi J.; Castrucci, Brian C.; Hearne, Shelley

    2016-01-01

    Context: Local health departments (LHDs) have historically not prioritized policy development, although it is one of the 3 core areas they address. One strategy that may influence policy in LHD jurisdictions is the formation of partnerships across sectors to work together on local public health policy. Design: We used a network approach to examine LHD local health policy partnerships across 15 large cities from the Big Cities Health Coalition. Setting/Participants: We surveyed the health departments and their partners about their working relationships in 5 policy areas: core local funding, tobacco control, obesity and chronic disease, violence and injury prevention, and infant mortality. Outcome Measures: Drawing on prior literature linking network structures with performance, we examined network density, transitivity, centralization and centrality, member diversity, and assortativity of ties. Results: Networks included an average of 21.8 organizations. Nonprofits and government agencies made up the largest proportions of the networks, with 28.8% and 21.7% of network members, whereas for-profits and foundations made up the smallest proportions in all of the networks, with just 1.2% and 2.4% on average. Mean values of density, transitivity, diversity, assortativity, centralization, and centrality showed similarity across policy areas and most LHDs. The tobacco control and obesity/chronic disease networks were densest and most diverse, whereas the infant mortality policy networks were the most centralized and had the highest assortativity. Core local funding policy networks had lower scores than other policy area networks by most network measures. Conclusion: Urban LHDs partner with organizations from diverse sectors to conduct local public health policy work. Network structures are similar across policy areas jurisdictions. Obesity and chronic disease, tobacco control, and infant mortality networks had structures consistent with higher performing networks, whereas

  3. Network theory-based analysis of risk interactions in large engineering projects

    International Nuclear Information System (INIS)

    Fang, Chao; Marle, Franck; Zio, Enrico; Bocquet, Jean-Claude

    2012-01-01

    This paper presents an approach based on network theory to deal with risk interactions in large engineering projects. Indeed, such projects are exposed to numerous and interdependent risks of various nature, which makes their management more difficult. In this paper, a topological analysis based on network theory is presented, which aims at identifying key elements in the structure of interrelated risks potentially affecting a large engineering project. This analysis serves as a powerful complement to classical project risk analysis. Its originality lies in the application of some network theory indicators to the project risk management field. The construction of the risk network requires the involvement of the project manager and other team members assigned to the risk management process. Its interpretation improves their understanding of risks and their potential interactions. The outcomes of the analysis provide a support for decision-making regarding project risk management. An example of application to a real large engineering project is presented. The conclusion is that some new insights can be found about risks, about their interactions and about the global potential behavior of the project. - Highlights: ► The method addresses the modeling of complexity in project risk analysis. ► Network theory indicators enable other risks than classical criticality analysis to be highlighted. ► This topological analysis improves project manager's understanding of risks and risk interactions. ► This helps project manager to make decisions considering the position in the risk network. ► An application to a real tramway implementation project in a city is provided.

  4. FUSE: a profit maximization approach for functional summarization of biological networks

    Directory of Open Access Journals (Sweden)

    Seah Boon-Siew

    2012-03-01

    Full Text Available Abstract Background The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL principle to maximize information gain of the summary graph while satisfying the level of detail constraint. Results We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. Conclusion By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

  5. A Network Biology Approach to Discover the Molecular Biomarker Associated with Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Liwei Zhuang

    2014-01-01

    Full Text Available In recent years, high throughput technologies such as microarray platform have provided a new avenue for hepatocellular carcinoma (HCC investigation. Traditionally, gene sets enrichment analysis of survival related genes is commonly used to reveal the underlying functional mechanisms. However, this approach usually produces too many candidate genes and cannot discover detailed signaling transduction cascades, which greatly limits their clinical application such as biomarker development. In this study, we have proposed a network biology approach to discover novel biomarkers from multidimensional omics data. This approach effectively combines clinical survival data with topological characteristics of human protein interaction networks and patients expression profiling data. It can produce novel network based biomarkers together with biological understanding of molecular mechanism. We have analyzed eighty HCC expression profiling arrays and identified that extracellular matrix and programmed cell death are the main themes related to HCC progression. Compared with traditional enrichment analysis, this approach can provide concrete and testable hypothesis on functional mechanism. Furthermore, the identified subnetworks can potentially be used as suitable targets for therapeutic intervention in HCC.

  6. Loosening the shackles of scientific disciplines with network science. Reply to comments on "Network science of biological systems at different scales: A review"

    Science.gov (United States)

    Gosak, Marko; Markovič, Rene; Dolenšek, Jurij; Rupnik, Marjan Slak; Marhl, Marko; Stožer, Andraž; Perc, Matjaž

    2018-03-01

    We would like to thank all the experts for their insightful and very interesting comments that have been submitted in response to our review "Network science of biological systems at different scales" [1]. We are delighted with the number of comments that have been written, and even more so with the positive opinions that these comments communicate to the wider audience [2-9]. Although methods of network science have long proven their value in relevantly addressing various challenges in the biological sciences, such interdisciplinary research often still struggles for funding and recognition at many academic levels.

  7. Efficient network monitoring for large data acquisition systems

    International Nuclear Information System (INIS)

    Savu, D.O.; Martin, B.; Al-Shabibi, A.; Sjoen, R.; Batraneanu, S.M.; Stancu, S.N.

    2012-01-01

    Though constantly evolving and improving, the available network monitoring solutions have limitations when applied to the infrastructure of a high speed realtime data acquisition (DAQ) system. DAQ networks are particular computer networks where experts have to pay attention to both individual subsections as well as system wide traffic flows while monitoring the network. The ATLAS Network at the Large Hadron Collider (LHC) has more than 200 switches interconnecting 3500 hosts and totaling 8500 high speed links. The use of heterogeneous tools for monitoring various infrastructure parameters, in order to assure optimal DAQ system performance, proved to be a tedious and time consuming task for experts. To alleviate this problem we used our networking and DAQ expertise to build a flexible and scalable monitoring system providing an intuitive user interface with the same look and feel irrespective of the data provider that is used. Our system uses custom developed components for critical performance monitoring and seamlessly integrates complementary data from auxiliary tools, such as NAGIOS, information services or custom databases. A number of techniques (e.g. normalization, aggregation and data caching) were used in order to improve the user interface response time. The end result is a unified monitoring interface, for fast and uniform access to system statistics, which significantly reduced the time spent by experts for ad-hoc and post-mortem analysis. (authors)

  8. Episodic memory in aspects of large-scale brain networks

    Science.gov (United States)

    Jeong, Woorim; Chung, Chun Kee; Kim, June Sic

    2015-01-01

    Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment. PMID:26321939

  9. Episodic memory in aspects of large-scale brain networks

    Directory of Open Access Journals (Sweden)

    Woorim eJeong

    2015-08-01

    Full Text Available Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network. Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network. Altered patterns of functional connectivity among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment.

  10. Biological impacts and context of network theory

    Energy Technology Data Exchange (ETDEWEB)

    Almaas, E

    2007-01-05

    Many complex systems can be represented and analyzed as networks, and examples that have benefited from this approach span the natural sciences. For instance, we now know that systems as disparate as the World-Wide Web, the Internet, scientific collaborations, food webs, protein interactions and metabolism all have common features in their organization, the most salient of which are their scale-free connectivity distributions and their small-world behavior. The recent availability of large scale datasets that span the proteome or metabolome of an organism have made it possible to elucidate some of the organizational principles and rules that govern their function, robustness and evolution. We expect that combining the currently separate layers of information from gene regulatory-, signal transduction-, protein interaction- and metabolic networks will dramatically enhance our understanding of cellular function and dynamics.

  11. Developing A Large-Scale, Collaborative, Productive Geoscience Education Network

    Science.gov (United States)

    Manduca, C. A.; Bralower, T. J.; Egger, A. E.; Fox, S.; Ledley, T. S.; Macdonald, H.; Mcconnell, D. A.; Mogk, D. W.; Tewksbury, B. J.

    2012-12-01

    Over the past 15 years, the geoscience education community has grown substantially and developed broad and deep capacity for collaboration and dissemination of ideas. While this community is best viewed as emergent from complex interactions among changing educational needs and opportunities, we highlight the role of several large projects in the development of a network within this community. In the 1990s, three NSF projects came together to build a robust web infrastructure to support the production and dissemination of on-line resources: On The Cutting Edge (OTCE), Earth Exploration Toolbook, and Starting Point: Teaching Introductory Geoscience. Along with the contemporaneous Digital Library for Earth System Education, these projects engaged geoscience educators nationwide in exploring professional development experiences that produced lasting on-line resources, collaborative authoring of resources, and models for web-based support for geoscience teaching. As a result, a culture developed in the 2000s in which geoscience educators anticipated that resources for geoscience teaching would be shared broadly and that collaborative authoring would be productive and engaging. By this time, a diverse set of examples demonstrated the power of the web infrastructure in supporting collaboration, dissemination and professional development . Building on this foundation, more recent work has expanded both the size of the network and the scope of its work. Many large research projects initiated collaborations to disseminate resources supporting educational use of their data. Research results from the rapidly expanding geoscience education research community were integrated into the Pedagogies in Action website and OTCE. Projects engaged faculty across the nation in large-scale data collection and educational research. The Climate Literacy and Energy Awareness Network and OTCE engaged community members in reviewing the expanding body of on-line resources. Building Strong

  12. A multilevel layout algorithm for visualizing physical and genetic interaction networks, with emphasis on their modular organization

    Directory of Open Access Journals (Sweden)

    Tuikkala Johannes

    2012-03-01

    Full Text Available Abstract Background Graph drawing is an integral part of many systems biology studies, enabling visual exploration and mining of large-scale biological networks. While a number of layout algorithms are available in popular network analysis platforms, such as Cytoscape, it remains poorly understood how well their solutions reflect the underlying biological processes that give rise to the network connectivity structure. Moreover, visualizations obtained using conventional layout algorithms, such as those based on the force-directed drawing approach, may become uninformative when applied to larger networks with dense or clustered connectivity structure. Methods We implemented a modified layout plug-in, named Multilevel Layout, which applies the conventional layout algorithms within a multilevel optimization framework to better capture the hierarchical modularity of many biological networks. Using a wide variety of real life biological networks, we carried out a systematic evaluation of the method in comparison with other layout algorithms in Cytoscape. Results The multilevel approach provided both biologically relevant and visually pleasant layout solutions in most network types, hence complementing the layout options available in Cytoscape. In particular, it could improve drawing of large-scale networks of yeast genetic interactions and human physical interactions. In more general terms, the biological evaluation framework developed here enables one to assess the layout solutions from any existing or future graph drawing algorithm as well as to optimize their performance for a given network type or structure. Conclusions By making use of the multilevel modular organization when visualizing biological networks, together with the biological evaluation of the layout solutions, one can generate convenient visualizations for many network biology applications.

  13. VANESA - A Software Application for the Visualization and Analysis of Networks in Systems Biology Applications

    Directory of Open Access Journals (Sweden)

    Brinkrolf Christoph

    2014-06-01

    Full Text Available VANESA is a modeling software for the automatic reconstruction and analysis of biological networks based on life-science database information. Using VANESA, scientists are able to model any kind of biological processes and systems as biological networks. It is now possible for scientists to automatically reconstruct important molecular systems with information from the databases KEGG, MINT, IntAct, HPRD, and BRENDA. Additionally, experimental results can be expanded with database information to better analyze the investigated elements and processes in an overall context. Users also have the possibility to use graph theoretical approaches in VANESA to identify regulatory structures and significant actors within the modeled systems. These structures can then be further investigated in the Petri net environment of VANESA. It is platform-independent, free-of-charge, and available at http://vanesa.sf.net.

  14. Root Systems Biology: Integrative Modeling across Scales, from Gene Regulatory Networks to the Rhizosphere1

    Science.gov (United States)

    Hill, Kristine; Porco, Silvana; Lobet, Guillaume; Zappala, Susan; Mooney, Sacha; Draye, Xavier; Bennett, Malcolm J.

    2013-01-01

    Genetic and genomic approaches in model organisms have advanced our understanding of root biology over the last decade. Recently, however, systems biology and modeling have emerged as important approaches, as our understanding of root regulatory pathways has become more complex and interpreting pathway outputs has become less intuitive. To relate root genotype to phenotype, we must move beyond the examination of interactions at the genetic network scale and employ multiscale modeling approaches to predict emergent properties at the tissue, organ, organism, and rhizosphere scales. Understanding the underlying biological mechanisms and the complex interplay between systems at these different scales requires an integrative approach. Here, we describe examples of such approaches and discuss the merits of developing models to span multiple scales, from network to population levels, and to address dynamic interactions between plants and their environment. PMID:24143806

  15. A wireless sensor network design and evaluation for large structural strain field monitoring

    International Nuclear Information System (INIS)

    Qiu, Zixue; Wu, Jian; Yuan, Shenfang

    2011-01-01

    Structural strain changes under external environmental or mechanical loads are the main monitoring parameters in structural health monitoring or mechanical property tests. This paper presents a wireless sensor network designed for monitoring large structural strain field variation. First of all, a precision strain sensor node is designed for multi-channel strain gauge signal conditioning and wireless monitoring. In order to establish a synchronous strain data acquisition network, the cluster-star network synchronization method is designed in detail. To verify the functionality of the designed wireless network for strain field monitoring capability, a multi-point network evaluation system is developed for an experimental aluminum plate structure for load variation monitoring. Based on the precision wireless strain nodes, the wireless data acquisition network is deployed to synchronously gather, process and transmit strain gauge signals and monitor results under concentrated loads. This paper shows the efficiency of the wireless sensor network for large structural strain field monitoring

  16. Active self-testing noise measurement sensors for large-scale environmental sensor networks.

    Science.gov (United States)

    Domínguez, Federico; Cuong, Nguyen The; Reinoso, Felipe; Touhafi, Abdellah; Steenhaut, Kris

    2013-12-13

    Large-scale noise pollution sensor networks consist of hundreds of spatially distributed microphones that measure environmental noise. These networks provide historical and real-time environmental data to citizens and decision makers and are therefore a key technology to steer environmental policy. However, the high cost of certified environmental microphone sensors render large-scale environmental networks prohibitively expensive. Several environmental network projects have started using off-the-shelf low-cost microphone sensors to reduce their costs, but these sensors have higher failure rates and produce lower quality data. To offset this disadvantage, we developed a low-cost noise sensor that actively checks its condition and indirectly the integrity of the data it produces. The main design concept is to embed a 13 mm speaker in the noise sensor casing and, by regularly scheduling a frequency sweep, estimate the evolution of the microphone's frequency response over time. This paper presents our noise sensor's hardware and software design together with the results of a test deployment in a large-scale environmental network in Belgium. Our middle-range-value sensor (around €50) effectively detected all experienced malfunctions, in laboratory tests and outdoor deployments, with a few false positives. Future improvements could further lower the cost of our sensor below €10.

  17. Reorganizing Complex Network to Improve Large-Scale Multiagent Teamwork

    Directory of Open Access Journals (Sweden)

    Yang Xu

    2014-01-01

    Full Text Available Large-scale multiagent teamwork has been popular in various domains. Similar to human society infrastructure, agents only coordinate with some of the others, with a peer-to-peer complex network structure. Their organization has been proven as a key factor to influence their performance. To expedite team performance, we have analyzed that there are three key factors. First, complex network effects may be able to promote team performance. Second, coordination interactions coming from their sources are always trying to be routed to capable agents. Although they could be transferred across the network via different paths, their sources and sinks depend on the intrinsic nature of the team which is irrelevant to the network connections. In addition, the agents involved in the same plan often form a subteam and communicate with each other more frequently. Therefore, if the interactions between agents can be statistically recorded, we are able to set up an integrated network adjustment algorithm by combining the three key factors. Based on our abstracted teamwork simulations and the coordination statistics, we implemented the adaptive reorganization algorithm. The experimental results briefly support our design that the reorganized network is more capable of coordinating heterogeneous agents.

  18. Impact of biology knowledge on the conservation and management of large pelagic sharks

    OpenAIRE

    Yokoi, Hiroki; Ijima, Hirotaka; Ohshimo, Seiji; Yokawa, Kotaro

    2017-01-01

    Population growth rate, which depends on several biological parameters, is valuable information for the conservation and management of pelagic sharks, such as blue and shortfin mako sharks. However, reported biological parameters for estimating the population growth rates of these sharks differ by sex and display large variability. To estimate the appropriate population growth rate and clarify relationships between growth rate and relevant biological parameters, we developed a two-sex age-str...

  19. Locating inefficient links in a large-scale transportation network

    Science.gov (United States)

    Sun, Li; Liu, Like; Xu, Zhongzhi; Jie, Yang; Wei, Dong; Wang, Pu

    2015-02-01

    Based on data from geographical information system (GIS) and daily commuting origin destination (OD) matrices, we estimated the distribution of traffic flow in the San Francisco road network and studied Braess's paradox in a large-scale transportation network with realistic travel demand. We measured the variation of total travel time Δ T when a road segment is closed, and found that | Δ T | follows a power-law distribution if Δ T 0. This implies that most roads have a negligible effect on the efficiency of the road network, while the failure of a few crucial links would result in severe travel delays, and closure of a few inefficient links would counter-intuitively reduce travel costs considerably. Generating three theoretical networks, we discovered that the heterogeneously distributed travel demand may be the origin of the observed power-law distributions of | Δ T | . Finally, a genetic algorithm was used to pinpoint inefficient link clusters in the road network. We found that closing specific road clusters would further improve the transportation efficiency.

  20. Foundational perspectives on causality in large-scale brain networks

    Science.gov (United States)

    Mannino, Michael; Bressler, Steven L.

    2015-12-01

    A profusion of recent work in cognitive neuroscience has been concerned with the endeavor to uncover causal influences in large-scale brain networks. However, despite the fact that many papers give a nod to the important theoretical challenges posed by the concept of causality, this explosion of research has generally not been accompanied by a rigorous conceptual analysis of the nature of causality in the brain. This review provides both a descriptive and prescriptive account of the nature of causality as found within and between large-scale brain networks. In short, it seeks to clarify the concept of causality in large-scale brain networks both philosophically and scientifically. This is accomplished by briefly reviewing the rich philosophical history of work on causality, especially focusing on contributions by David Hume, Immanuel Kant, Bertrand Russell, and Christopher Hitchcock. We go on to discuss the impact that various interpretations of modern physics have had on our understanding of causality. Throughout all this, a central focus is the distinction between theories of deterministic causality (DC), whereby causes uniquely determine their effects, and probabilistic causality (PC), whereby causes change the probability of occurrence of their effects. We argue that, given the topological complexity of its large-scale connectivity, the brain should be considered as a complex system and its causal influences treated as probabilistic in nature. We conclude that PC is well suited for explaining causality in the brain for three reasons: (1) brain causality is often mutual; (2) connectional convergence dictates that only rarely is the activity of one neuronal population uniquely determined by another one; and (3) the causal influences exerted between neuronal populations may not have observable effects. A number of different techniques are currently available to characterize causal influence in the brain. Typically, these techniques quantify the statistical

  1. Impact of biology knowledge on the conservation and management of large pelagic sharks.

    Science.gov (United States)

    Yokoi, Hiroki; Ijima, Hirotaka; Ohshimo, Seiji; Yokawa, Kotaro

    2017-09-06

    Population growth rate, which depends on several biological parameters, is valuable information for the conservation and management of pelagic sharks, such as blue and shortfin mako sharks. However, reported biological parameters for estimating the population growth rates of these sharks differ by sex and display large variability. To estimate the appropriate population growth rate and clarify relationships between growth rate and relevant biological parameters, we developed a two-sex age-structured matrix population model and estimated the population growth rate using combinations of biological parameters. We addressed elasticity analysis and clarified the population growth rate sensitivity. For the blue shark, the estimated median population growth rate was 0.384 with a range of minimum and maximum values of 0.195-0.533, whereas those values of the shortfin mako shark were 0.102 and 0.007-0.318, respectively. The maturity age of male sharks had the largest impact for blue sharks, whereas that of female sharks had the largest impact for shortfin mako sharks. Hypotheses for the survival process of sharks also had a large impact on the population growth rate estimation. Both shark maturity age and survival rate were based on ageing validation data, indicating the importance of validating the quality of these data for the conservation and management of large pelagic sharks.

  2. New Algorithm and Software (BNOmics) for Inferring and Visualizing Bayesian Networks from Heterogeneous Big Biological and Genetic Data.

    Science.gov (United States)

    Gogoshin, Grigoriy; Boerwinkle, Eric; Rodin, Andrei S

    2017-04-01

    Bayesian network (BN) reconstruction is a prototypical systems biology data analysis approach that has been successfully used to reverse engineer and model networks reflecting different layers of biological organization (ranging from genetic to epigenetic to cellular pathway to metabolomic). It is especially relevant in the context of modern (ongoing and prospective) studies that generate heterogeneous high-throughput omics datasets. However, there are both theoretical and practical obstacles to the seamless application of BN modeling to such big data, including computational inefficiency of optimal BN structure search algorithms, ambiguity in data discretization, mixing data types, imputation and validation, and, in general, limited scalability in both reconstruction and visualization of BNs. To overcome these and other obstacles, we present BNOmics, an improved algorithm and software toolkit for inferring and analyzing BNs from omics datasets. BNOmics aims at comprehensive systems biology-type data exploration, including both generating new biological hypothesis and testing and validating the existing ones. Novel aspects of the algorithm center around increasing scalability and applicability to varying data types (with different explicit and implicit distributional assumptions) within the same analysis framework. An output and visualization interface to widely available graph-rendering software is also included. Three diverse applications are detailed. BNOmics was originally developed in the context of genetic epidemiology data and is being continuously optimized to keep pace with the ever-increasing inflow of available large-scale omics datasets. As such, the software scalability and usability on the less than exotic computer hardware are a priority, as well as the applicability of the algorithm and software to the heterogeneous datasets containing many data types-single-nucleotide polymorphisms and other genetic/epigenetic/transcriptome variables, metabolite

  3. Data management strategies for multinational large-scale systems biology projects.

    Science.gov (United States)

    Wruck, Wasco; Peuker, Martin; Regenbrecht, Christian R A

    2014-01-01

    Good accessibility of publicly funded research data is essential to secure an open scientific system and eventually becomes mandatory [Wellcome Trust will Penalise Scientists Who Don't Embrace Open Access. The Guardian 2012]. By the use of high-throughput methods in many research areas from physics to systems biology, large data collections are increasingly important as raw material for research. Here, we present strategies worked out by international and national institutions targeting open access to publicly funded research data via incentives or obligations to share data. Funding organizations such as the British Wellcome Trust therefore have developed data sharing policies and request commitment to data management and sharing in grant applications. Increased citation rates are a profound argument for sharing publication data. Pre-publication sharing might be rewarded by a data citation credit system via digital object identifiers (DOIs) which have initially been in use for data objects. Besides policies and incentives, good practice in data management is indispensable. However, appropriate systems for data management of large-scale projects for example in systems biology are hard to find. Here, we give an overview of a selection of open-source data management systems proved to be employed successfully in large-scale projects.

  4. Extraction of drainage networks from large terrain datasets using high throughput computing

    Science.gov (United States)

    Gong, Jianya; Xie, Jibo

    2009-02-01

    Advanced digital photogrammetry and remote sensing technology produces large terrain datasets (LTD). How to process and use these LTD has become a big challenge for GIS users. Extracting drainage networks, which are basic for hydrological applications, from LTD is one of the typical applications of digital terrain analysis (DTA) in geographical information applications. Existing serial drainage algorithms cannot deal with large data volumes in a timely fashion, and few GIS platforms can process LTD beyond the GB size. High throughput computing (HTC), a distributed parallel computing mode, is proposed to improve the efficiency of drainage networks extraction from LTD. Drainage network extraction using HTC involves two key issues: (1) how to decompose the large DEM datasets into independent computing units and (2) how to merge the separate outputs into a final result. A new decomposition method is presented in which the large datasets are partitioned into independent computing units using natural watershed boundaries instead of using regular 1-dimensional (strip-wise) and 2-dimensional (block-wise) decomposition. Because the distribution of drainage networks is strongly related to watershed boundaries, the new decomposition method is more effective and natural. The method to extract natural watershed boundaries was improved by using multi-scale DEMs instead of single-scale DEMs. A HTC environment is employed to test the proposed methods with real datasets.

  5. Large-Scale Brain Networks Supporting Divided Attention across Spatial Locations and Sensory Modalities.

    Science.gov (United States)

    Santangelo, Valerio

    2018-01-01

    Higher-order cognitive processes were shown to rely on the interplay between large-scale neural networks. However, brain networks involved with the capability to split attentional resource over multiple spatial locations and multiple stimuli or sensory modalities have been largely unexplored to date. Here I re-analyzed data from Santangelo et al. (2010) to explore the causal interactions between large-scale brain networks during divided attention. During fMRI scanning, participants monitored streams of visual and/or auditory stimuli in one or two spatial locations for detection of occasional targets. This design allowed comparing a condition in which participants monitored one stimulus/modality (either visual or auditory) in two spatial locations vs. a condition in which participants monitored two stimuli/modalities (both visual and auditory) in one spatial location. The analysis of the independent components (ICs) revealed that dividing attentional resources across two spatial locations necessitated a brain network involving the left ventro- and dorso-lateral prefrontal cortex plus the posterior parietal cortex, including the intraparietal sulcus (IPS) and the angular gyrus, bilaterally. The analysis of Granger causality highlighted that the activity of lateral prefrontal regions were predictive of the activity of all of the posteriors parietal nodes. By contrast, dividing attention across two sensory modalities necessitated a brain network including nodes belonging to the dorsal frontoparietal network, i.e., the bilateral frontal eye-fields (FEF) and IPS, plus nodes belonging to the salience network, i.e., the anterior cingulated cortex and the left and right anterior insular cortex (aIC). The analysis of Granger causality highlights a tight interdependence between the dorsal frontoparietal and salience nodes in trials requiring divided attention between different sensory modalities. The current findings therefore highlighted a dissociation among brain networks

  6. Large-Scale Brain Networks Supporting Divided Attention across Spatial Locations and Sensory Modalities

    Directory of Open Access Journals (Sweden)

    Valerio Santangelo

    2018-02-01

    Full Text Available Higher-order cognitive processes were shown to rely on the interplay between large-scale neural networks. However, brain networks involved with the capability to split attentional resource over multiple spatial locations and multiple stimuli or sensory modalities have been largely unexplored to date. Here I re-analyzed data from Santangelo et al. (2010 to explore the causal interactions between large-scale brain networks during divided attention. During fMRI scanning, participants monitored streams of visual and/or auditory stimuli in one or two spatial locations for detection of occasional targets. This design allowed comparing a condition in which participants monitored one stimulus/modality (either visual or auditory in two spatial locations vs. a condition in which participants monitored two stimuli/modalities (both visual and auditory in one spatial location. The analysis of the independent components (ICs revealed that dividing attentional resources across two spatial locations necessitated a brain network involving the left ventro- and dorso-lateral prefrontal cortex plus the posterior parietal cortex, including the intraparietal sulcus (IPS and the angular gyrus, bilaterally. The analysis of Granger causality highlighted that the activity of lateral prefrontal regions were predictive of the activity of all of the posteriors parietal nodes. By contrast, dividing attention across two sensory modalities necessitated a brain network including nodes belonging to the dorsal frontoparietal network, i.e., the bilateral frontal eye-fields (FEF and IPS, plus nodes belonging to the salience network, i.e., the anterior cingulated cortex and the left and right anterior insular cortex (aIC. The analysis of Granger causality highlights a tight interdependence between the dorsal frontoparietal and salience nodes in trials requiring divided attention between different sensory modalities. The current findings therefore highlighted a dissociation among

  7. Maximal planar networks with large clustering coefficient and power-law degree distribution

    International Nuclear Information System (INIS)

    Zhou Tao; Yan Gang; Wang Binghong

    2005-01-01

    In this article, we propose a simple rule that generates scale-free networks with very large clustering coefficient and very small average distance. These networks are called random Apollonian networks (RANs) as they can be considered as a variation of Apollonian networks. We obtain the analytic results of power-law exponent γ=3 and clustering coefficient C=(46/3)-36 ln (3/2)≅0.74, which agree with the simulation results very well. We prove that the increasing tendency of average distance of RANs is a little slower than the logarithm of the number of nodes in RANs. Since most real-life networks are both scale-free and small-world networks, RANs may perform well in mimicking the reality. The RANs possess hierarchical structure as C(k)∼k -1 that are in accord with the observations of many real-life networks. In addition, we prove that RANs are maximal planar networks, which are of particular practicability for layout of printed circuits and so on. The percolation and epidemic spreading process are also studied and the comparisons between RANs and Barabasi-Albert (BA) as well as Newman-Watts (NW) networks are shown. We find that, when the network order N (the total number of nodes) is relatively small (as N∼10 4 ), the performance of RANs under intentional attack is not sensitive to N, while that of BA networks is much affected by N. And the diseases spread slower in RANs than BA networks in the early stage of the suseptible-infected process, indicating that the large clustering coefficient may slow the spreading velocity, especially in the outbreaks

  8. Evidence for the additions of clustered interacting nodes during the evolution of protein interaction networks from network motifs

    Directory of Open Access Journals (Sweden)

    Guo Hao

    2011-05-01

    Full Text Available Abstract Background High-throughput screens have revealed large-scale protein interaction networks defining most cellular functions. How the proteins were added to the protein interaction network during its growth is a basic and important issue. Network motifs represent the simplest building blocks of cellular machines and are of biological significance. Results Here we study the evolution of protein interaction networks from the perspective of network motifs. We find that in current protein interaction networks, proteins of the same age class tend to form motifs and such co-origins of motif constituents are affected by their topologies and biological functions. Further, we find that the proteins within motifs whose constituents are of the same age class tend to be densely interconnected, co-evolve and share the same biological functions, and these motifs tend to be within protein complexes. Conclusions Our findings provide novel evidence for the hypothesis of the additions of clustered interacting nodes and point out network motifs, especially the motifs with the dense topology and specific function may play important roles during this process. Our results suggest functional constraints may be the underlying driving force for such additions of clustered interacting nodes.

  9. Modeling Temporal Behavior in Large Networks: A Dynamic Mixed-Membership Model

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, R; Gallagher, B; Neville, J; Henderson, K

    2011-11-11

    Given a large time-evolving network, how can we model and characterize the temporal behaviors of individual nodes (and network states)? How can we model the behavioral transition patterns of nodes? We propose a temporal behavior model that captures the 'roles' of nodes in the graph and how they evolve over time. The proposed dynamic behavioral mixed-membership model (DBMM) is scalable, fully automatic (no user-defined parameters), non-parametric/data-driven (no specific functional form or parameterization), interpretable (identifies explainable patterns), and flexible (applicable to dynamic and streaming networks). Moreover, the interpretable behavioral roles are generalizable, computationally efficient, and natively supports attributes. We applied our model for (a) identifying patterns and trends of nodes and network states based on the temporal behavior, (b) predicting future structural changes, and (c) detecting unusual temporal behavior transitions. We use eight large real-world datasets from different time-evolving settings (dynamic and streaming). In particular, we model the evolving mixed-memberships and the corresponding behavioral transitions of Twitter, Facebook, IP-Traces, Email (University), Internet AS, Enron, Reality, and IMDB. The experiments demonstrate the scalability, flexibility, and effectiveness of our model for identifying interesting patterns, detecting unusual structural transitions, and predicting the future structural changes of the network and individual nodes.

  10. CellNet: Network Biology Applied to Stem Cell Engineering

    Science.gov (United States)

    Cahan, Patrick; Li, Hu; Morris, Samantha A.; da Rocha, Edroaldo Lummertz; Daley, George Q.; Collins, James J.

    2014-01-01

    SUMMARY Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population, and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. PMID:25126793

  11. CellNet: network biology applied to stem cell engineering.

    Science.gov (United States)

    Cahan, Patrick; Li, Hu; Morris, Samantha A; Lummertz da Rocha, Edroaldo; Daley, George Q; Collins, James J

    2014-08-14

    Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Predicting Protein Function via Semantic Integration of Multiple Networks.

    Science.gov (United States)

    Yu, Guoxian; Fu, Guangyuan; Wang, Jun; Zhu, Hailong

    2016-01-01

    Determining the biological functions of proteins is one of the key challenges in the post-genomic era. The rapidly accumulated large volumes of proteomic and genomic data drives to develop computational models for automatically predicting protein function in large scale. Recent approaches focus on integrating multiple heterogeneous data sources and they often get better results than methods that use single data source alone. In this paper, we investigate how to integrate multiple biological data sources with the biological knowledge, i.e., Gene Ontology (GO), for protein function prediction. We propose a method, called SimNet, to Semantically integrate multiple functional association Networks derived from heterogenous data sources. SimNet firstly utilizes GO annotations of proteins to capture the semantic similarity between proteins and introduces a semantic kernel based on the similarity. Next, SimNet constructs a composite network, obtained as a weighted summation of individual networks, and aligns the network with the kernel to get the weights assigned to individual networks. Then, it applies a network-based classifier on the composite network to predict protein function. Experiment results on heterogenous proteomic data sources of Yeast, Human, Mouse, and Fly show that, SimNet not only achieves better (or comparable) results than other related competitive approaches, but also takes much less time. The Matlab codes of SimNet are available at https://sites.google.com/site/guoxian85/simnet.

  13. Zebrafish whole-adult-organism chemogenomics for large-scale predictive and discovery chemical biology.

    Directory of Open Access Journals (Sweden)

    Siew Hong Lam

    2008-07-01

    Full Text Available The ability to perform large-scale, expression-based chemogenomics on whole adult organisms, as in invertebrate models (worm and fly, is highly desirable for a vertebrate model but its feasibility and potential has not been demonstrated. We performed expression-based chemogenomics on the whole adult organism of a vertebrate model, the zebrafish, and demonstrated its potential for large-scale predictive and discovery chemical biology. Focusing on two classes of compounds with wide implications to human health, polycyclic (halogenated aromatic hydrocarbons [P(HAHs] and estrogenic compounds (ECs, we generated robust prediction models that can discriminate compounds of the same class from those of different classes in two large independent experiments. The robust expression signatures led to the identification of biomarkers for potent aryl hydrocarbon receptor (AHR and estrogen receptor (ER agonists, respectively, and were validated in multiple targeted tissues. Knowledge-based data mining of human homologs of zebrafish genes revealed highly conserved chemical-induced biological responses/effects, health risks, and novel biological insights associated with AHR and ER that could be inferred to humans. Thus, our study presents an effective, high-throughput strategy of capturing molecular snapshots of chemical-induced biological states of a whole adult vertebrate that provides information on biomarkers of effects, deregulated signaling pathways, and possible affected biological functions, perturbed physiological systems, and increased health risks. These findings place zebrafish in a strategic position to bridge the wide gap between cell-based and rodent models in chemogenomics research and applications, especially in preclinical drug discovery and toxicology.

  14. Software Defined Optics and Networking for Large Scale Data Centers

    DEFF Research Database (Denmark)

    Mehmeri, Victor; Andrus, Bogdan-Mihai; Tafur Monroy, Idelfonso

    Big data imposes correlations of large amounts of information between numerous systems and databases. This leads to large dynamically changing flows and traffic patterns between clusters and server racks that result in a decrease of the quality of transmission and degraded application performance....... Highly interconnected topologies combined with flexible, on demand network configuration can become a solution to the ever-increasing dynamic traffic...

  15. Localization Algorithm Based on a Spring Model (LASM for Large Scale Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Shuai Li

    2008-03-01

    Full Text Available A navigation method for a lunar rover based on large scale wireless sensornetworks is proposed. To obtain high navigation accuracy and large exploration area, highnode localization accuracy and large network scale are required. However, thecomputational and communication complexity and time consumption are greatly increasedwith the increase of the network scales. A localization algorithm based on a spring model(LASM method is proposed to reduce the computational complexity, while maintainingthe localization accuracy in large scale sensor networks. The algorithm simulates thedynamics of physical spring system to estimate the positions of nodes. The sensor nodesare set as particles with masses and connected with neighbor nodes by virtual springs. Thevirtual springs will force the particles move to the original positions, the node positionscorrespondingly, from the randomly set positions. Therefore, a blind node position can bedetermined from the LASM algorithm by calculating the related forces with the neighbornodes. The computational and communication complexity are O(1 for each node, since thenumber of the neighbor nodes does not increase proportionally with the network scale size.Three patches are proposed to avoid local optimization, kick out bad nodes and deal withnode variation. Simulation results show that the computational and communicationcomplexity are almost constant despite of the increase of the network scale size. The time consumption has also been proven to remain almost constant since the calculation steps arealmost unrelated with the network scale size.

  16. Composition and structure of a large online social network in The Netherlands.

    Directory of Open Access Journals (Sweden)

    Rense Corten

    Full Text Available Limitations in data collection have long been an obstacle in research on friendship networks. Most earlier studies use either a sample of ego-networks, or complete network data on a relatively small group (e.g., a single organization. The rise of online social networking services such as Friendster and Facebook, however, provides researchers with opportunities to study friendship networks on a much larger scale. This study uses complete network data from Hyves, a popular online social networking service in The Netherlands, comprising over eight million members and over 400 million online friendship relations. In the first study of its kind for The Netherlands, I examine the structure of this network in terms of the degree distribution, characteristic path length, clustering, and degree assortativity. Results indicate that this network shares features of other large complex networks, but also deviates in other respects. In addition, a comparison with other online social networks shows that these networks show remarkable similarities.

  17. Composition and structure of a large online social network in The Netherlands.

    Science.gov (United States)

    Corten, Rense

    2012-01-01

    Limitations in data collection have long been an obstacle in research on friendship networks. Most earlier studies use either a sample of ego-networks, or complete network data on a relatively small group (e.g., a single organization). The rise of online social networking services such as Friendster and Facebook, however, provides researchers with opportunities to study friendship networks on a much larger scale. This study uses complete network data from Hyves, a popular online social networking service in The Netherlands, comprising over eight million members and over 400 million online friendship relations. In the first study of its kind for The Netherlands, I examine the structure of this network in terms of the degree distribution, characteristic path length, clustering, and degree assortativity. Results indicate that this network shares features of other large complex networks, but also deviates in other respects. In addition, a comparison with other online social networks shows that these networks show remarkable similarities.

  18. Notes on a PDE system for biological network formation

    KAUST Repository

    Haskovec, Jan

    2016-01-22

    We present new analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transport networks. The model describes the pressure field using a Darcy’s type equation and the dynamics of the conductance network under pressure force effects. Randomness in the material structure is represented by a linear diffusion term and conductance relaxation by an algebraic decay term. The analytical part extends the results of Haskovec et al. (2015) regarding the existence of weak and mild solutions to the whole range of meaningful relaxation exponents. Moreover, we prove finite time extinction or break-down of solutions in the spatially one-dimensional setting for certain ranges of the relaxation exponent. We also construct stationary solutions for the case of vanishing diffusion and critical value of the relaxation exponent, using a variational formulation and a penalty method. The analytical part is complemented by extensive numerical simulations. We propose a discretization based on mixed finite elements and study the qualitative properties of network structures for various parameter values. Furthermore, we indicate numerically that some analytical results proved for the spatially one-dimensional setting are likely to be valid also in several space dimensions.

  19. Asymptotic Analysis of Large Cooperative Relay Networks Using Random Matrix Theory

    Directory of Open Access Journals (Sweden)

    H. Poor

    2008-04-01

    Full Text Available Cooperative transmission is an emerging communication technology that takes advantage of the broadcast nature of wireless channels. In cooperative transmission, the use of relays can create a virtual antenna array so that multiple-input/multiple-output (MIMO techniques can be employed. Most existing work in this area has focused on the situation in which there are a small number of sources and relays and a destination. In this paper, cooperative relay networks with large numbers of nodes are analyzed, and in particular the asymptotic performance improvement of cooperative transmission over direction transmission and relay transmission is analyzed using random matrix theory. The key idea is to investigate the eigenvalue distributions related to channel capacity and to analyze the moments of this distribution in large wireless networks. A performance upper bound is derived, the performance in the low signal-to-noise-ratio regime is analyzed, and two approximations are obtained for high and low relay-to-destination link qualities, respectively. Finally, simulations are provided to validate the accuracy of the analytical results. The analysis in this paper provides important tools for the understanding and the design of large cooperative wireless networks.

  20. Supramolecular assembly of biological molecules purified from bovine nerve cells: from microtubule bundles and necklaces to neurofilament networks

    International Nuclear Information System (INIS)

    Needleman, Daniel J; Jones, Jayna B; Raviv, Uri; Ojeda-Lopez, Miguel A; Miller, H P; Li, Y; Wilson, L; Safinya, C R

    2005-01-01

    With the completion of the human genome project, the biosciences community is beginning the daunting task of understanding the structures and functions of a large number of interacting biological macromolecules. Examples include the interacting molecules involved in the process of DNA condensation during the cell cycle, and in the formation of bundles and networks of filamentous actin proteins in cell attachment, motility and cytokinesis. In this proceedings paper we present examples of supramolecular assembly based on proteins derived from the vertebrate nerve cell cytoskeleton. The axonal cytoskeleton in vertebrate neurons provides a rich example of bundles and networks of neurofilaments, microtubules (MTs) and filamentous actin, where the nature of the interactions, structures, and structure-function correlations remains poorly understood. We describe synchrotron x-ray diffraction, electron microscopy, and optical imaging data, in reconstituted protein systems purified from bovine central nervous system, which reveal unexpected structures not predicted by current electrostatic theories of polyelectrolyte bundling, including three-dimensional MT bundles and two-dimensional MT necklaces

  1. Modeling Wireless Sensor Networks for Monitoring in Biological Processes

    DEFF Research Database (Denmark)

    Nadimi, Esmaeil

    parameters, as the use of wired sensors is impractical. In this thesis, a ZigBee based wireless sensor network was employed and only a part of the herd was monitored, as monitoring each individual animal in a large herd under practical conditions is inefficient. Investigations to show that the monitored...... (MMAE) approach to the data resulted in the highest classification success rate, due to the use of precise forth-order mathematical models which relate the feed offer to the pitch angle of the neck. This thesis shows that wireless sensor networks can be successfully employed to monitor the behavior...

  2. Scalable and Fully Distributed Localization in Large-Scale Sensor Networks

    Directory of Open Access Journals (Sweden)

    Miao Jin

    2017-06-01

    Full Text Available This work proposes a novel connectivity-based localization algorithm, well suitable for large-scale sensor networks with complex shapes and a non-uniform nodal distribution. In contrast to current state-of-the-art connectivity-based localization methods, the proposed algorithm is highly scalable with linear computation and communication costs with respect to the size of the network; and fully distributed where each node only needs the information of its neighbors without cumbersome partitioning and merging process. The algorithm is theoretically guaranteed and numerically stable. Moreover, the algorithm can be readily extended to the localization of networks with a one-hop transmission range distance measurement, and the propagation of the measurement error at one sensor node is limited within a small area of the network around the node. Extensive simulations and comparison with other methods under various representative network settings are carried out, showing the superior performance of the proposed algorithm.

  3. Large-Scale Analysis of Network Bistability for Human Cancers

    Science.gov (United States)

    Shiraishi, Tetsuya; Matsuyama, Shinako; Kitano, Hiroaki

    2010-01-01

    Protein–protein interaction and gene regulatory networks are likely to be locked in a state corresponding to a disease by the behavior of one or more bistable circuits exhibiting switch-like behavior. Sets of genes could be over-expressed or repressed when anomalies due to disease appear, and the circuits responsible for this over- or under-expression might persist for as long as the disease state continues. This paper shows how a large-scale analysis of network bistability for various human cancers can identify genes that can potentially serve as drug targets or diagnosis biomarkers. PMID:20628618

  4. Ontology-supported research on vaccine efficacy, safety and integrative biological networks.

    Science.gov (United States)

    He, Yongqun

    2014-07-01

    While vaccine efficacy and safety research has dramatically progressed with the methods of in silico prediction and data mining, many challenges still exist. A formal ontology is a human- and computer-interpretable set of terms and relations that represent entities in a specific domain and how these terms relate to each other. Several community-based ontologies (including Vaccine Ontology, Ontology of Adverse Events and Ontology of Vaccine Adverse Events) have been developed to support vaccine and adverse event representation, classification, data integration, literature mining of host-vaccine interaction networks, and analysis of vaccine adverse events. The author further proposes minimal vaccine information standards and their ontology representations, ontology-based linked open vaccine data and meta-analysis, an integrative One Network ('OneNet') Theory of Life, and ontology-based approaches to study and apply the OneNet theory. In the Big Data era, these proposed strategies provide a novel framework for advanced data integration and analysis of fundamental biological networks including vaccine immune mechanisms.

  5. Autonomous management of a recursive area hierarchy for large scale wireless sensor networks using multiple parents

    Energy Technology Data Exchange (ETDEWEB)

    Cree, Johnathan Vee [Washington State Univ., Pullman, WA (United States); Delgado-Frias, Jose [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-03-01

    Large scale wireless sensor networks have been proposed for applications ranging from anomaly detection in an environment to vehicle tracking. Many of these applications require the networks to be distributed across a large geographic area while supporting three to five year network lifetimes. In order to support these requirements large scale wireless sensor networks of duty-cycled devices need a method of efficient and effective autonomous configuration/maintenance. This method should gracefully handle the synchronization tasks duty-cycled networks. Further, an effective configuration solution needs to recognize that in-network data aggregation and analysis presents significant benefits to wireless sensor network and should configure the network in a way such that said higher level functions benefit from the logically imposed structure. NOA, the proposed configuration and maintenance protocol, provides a multi-parent hierarchical logical structure for the network that reduces the synchronization workload. It also provides higher level functions with significant inherent benefits such as but not limited to: removing network divisions that are created by single-parent hierarchies, guarantees for when data will be compared in the hierarchy, and redundancies for communication as well as in-network data aggregation/analysis/storage.

  6. Large-scale functional networks connect differently for processing words and symbol strings.

    Science.gov (United States)

    Liljeström, Mia; Vartiainen, Johanna; Kujala, Jan; Salmelin, Riitta

    2018-01-01

    Reconfigurations of synchronized large-scale networks are thought to be central neural mechanisms that support cognition and behavior in the human brain. Magnetoencephalography (MEG) recordings together with recent advances in network analysis now allow for sub-second snapshots of such networks. In the present study, we compared frequency-resolved functional connectivity patterns underlying reading of single words and visual recognition of symbol strings. Word reading emphasized coherence in a left-lateralized network with nodes in classical perisylvian language regions, whereas symbol processing recruited a bilateral network, including connections between frontal and parietal regions previously associated with spatial attention and visual working memory. Our results illustrate the flexible nature of functional networks, whereby processing of different form categories, written words vs. symbol strings, leads to the formation of large-scale functional networks that operate at distinct oscillatory frequencies and incorporate task-relevant regions. These results suggest that category-specific processing should be viewed not so much as a local process but as a distributed neural process implemented in signature networks. For words, increased coherence was detected particularly in the alpha (8-13 Hz) and high gamma (60-90 Hz) frequency bands, whereas increased coherence for symbol strings was observed in the high beta (21-29 Hz) and low gamma (30-45 Hz) frequency range. These findings attest to the role of coherence in specific frequency bands as a general mechanism for integrating stimulus-dependent information across brain regions.

  7. Unified Alignment of Protein-Protein Interaction Networks.

    Science.gov (United States)

    Malod-Dognin, Noël; Ban, Kristina; Pržulj, Nataša

    2017-04-19

    Paralleling the increasing availability of protein-protein interaction (PPI) network data, several network alignment methods have been proposed. Network alignments have been used to uncover functionally conserved network parts and to transfer annotations. However, due to the computational intractability of the network alignment problem, aligners are heuristics providing divergent solutions and no consensus exists on a gold standard, or which scoring scheme should be used to evaluate them. We comprehensively evaluate the alignment scoring schemes and global network aligners on large scale PPI data and observe that three methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically and biologically coherent alignments. We study the collective behaviour of network aligners and observe that PPI networks are almost entirely aligned with a handful of aligners that we unify into a new tool, Ulign. Ulign enables complete alignment of two networks, which traditional global and local aligners fail to do. Also, multiple mappings of Ulign define biologically relevant soft clusterings of proteins in PPI networks, which may be used for refining the transfer of annotations across networks. Hence, PPI networks are already well investigated by current aligners, so to gain additional biological insights, a paradigm shift is needed. We propose such a shift come from aligning all available data types collectively rather than any particular data type in isolation from others.

  8. Error rate degradation due to switch crosstalk in large modular switched optical networks

    DEFF Research Database (Denmark)

    Saxtoft, Christian; Chidgey, P.

    1993-01-01

    A theoretical model of an optical network incorporating wavelength selective elements, amplifiers, couplers and switches is presented. The model is used to evaluate a large modular switch optical network that provides the capability of adapting easily to changes in network traffic requirements. T....... The network dimensions are shown to be limited by the optical crosstalk in the switch matrices and by the polarization dependent loss in the optical components...

  9. Spectral Methods for Immunization of Large Networks

    Directory of Open Access Journals (Sweden)

    Muhammad Ahmad

    2017-11-01

    Full Text Available Given a network of nodes, minimizing the spread of a contagion using a limited budget is a well-studied problem with applications in network security, viral marketing, social networks, and public health. In real graphs, virus may infect a node which in turn infects its neighbour nodes and this may trigger an epidemic in the whole graph. The goal thus is to select the best k nodes (budget constraint that are immunized (vaccinated, screened, filtered so as the remaining graph is less prone to the epidemic. It is known that the problem is, in all practical models, computationally intractable even for moderate sized graphs. In this paper we employ ideas from spectral graph theory to define relevance and importance of nodes. Using novel graph theoretic techniques, we then design an efficient approximation algorithm to immunize the graph. Theoretical guarantees on the running time of our algorithm show that it is more efficient than any other known solution in the literature. We test the performance of our algorithm on several real world graphs. Experiments show that our algorithm scales well for large graphs and outperforms state of the art algorithms both in quality (containment of epidemic and efficiency (runtime and space complexity.

  10. A multilevel layout algorithm for visualizing physical and genetic interaction networks, with emphasis on their modular organization

    OpenAIRE

    Tuikkala, Johannes; Vähämaa, Heidi; Salmela, Pekka; Nevalainen, Olli S; Aittokallio, Tero

    2012-01-01

    Abstract Background Graph drawing is an integral part of many systems biology studies, enabling visual exploration and mining of large-scale biological networks. While a number of layout algorithms are available in popular network analysis platforms, such as Cytoscape, it remains poorly understood how well their solutions reflect the underlying biological processes that give rise to the network connectivity structure. Moreover, visualizations obtained using conventional layout algorithms, suc...

  11. Functional asynchronous networks: Factorization of dynamics and function

    Directory of Open Access Journals (Sweden)

    Bick Christian

    2016-01-01

    Full Text Available In this note we describe the theory of functional asynchronous networks and one of the main results, the Modularization of Dynamics Theorem, which for a large class of functional asynchronous networks gives a factorization of dynamics in terms of constituent subnetworks. For these networks we can give a complete description of the network function in terms of the function of the events comprising the network and thereby answer a question originally raised by Alon in the context of biological networks.

  12. Why Traditional Expository Teaching-Learning Approaches May Founder? An Experimental Examination of Neural Networks in Biology Learning

    Science.gov (United States)

    Lee, Jun-Ki; Kwon, Yong-Ju

    2011-01-01

    Using functional magnetic resonance imaging (fMRI), this study investigates and discusses neurological explanations for, and the educational implications of, the neural network activations involved in hypothesis-generating and hypothesis-understanding for biology education. Two sets of task paradigms about biological phenomena were designed:…

  13. A comparative analysis on computational methods for fitting an ERGM to biological network data

    Directory of Open Access Journals (Sweden)

    Sudipta Saha

    2015-03-01

    Full Text Available Exponential random graph models (ERGM based on graph theory are useful in studying global biological network structure using its local properties. However, computational methods for fitting such models are sensitive to the type, structure and the number of the local features of a network under study. In this paper, we compared computational methods for fitting an ERGM with local features of different types and structures. Two commonly used methods, such as the Markov Chain Monte Carlo Maximum Likelihood Estimation and the Maximum Pseudo Likelihood Estimation are considered for estimating the coefficients of network attributes. We compared the estimates of observed network to our random simulated network using both methods under ERGM. The motivation was to ascertain the extent to which an observed network would deviate from a randomly simulated network if the physical numbers of attributes were approximately same. Cut-off points of some common attributes of interest for different order of nodes were determined through simulations. We implemented our method to a known regulatory network database of Escherichia coli (E. coli.

  14. Fundamentals of complex networks models, structures and dynamics

    CERN Document Server

    Chen, Guanrong; Li, Xiang

    2014-01-01

    Complex networks such as the Internet, WWW, transportationnetworks, power grids, biological neural networks, and scientificcooperation networks of all kinds provide challenges for futuretechnological development. In particular, advanced societies havebecome dependent on large infrastructural networks to an extentbeyond our capability to plan (modeling) and to operate (control).The recent spate of collapses in power grids and ongoing virusattacks on the Internet illustrate the need for knowledge aboutmodeling, analysis of behaviors, optimized planning and performancecontrol in such networks. F

  15. Usefulness and limitations of dK random graph models to predict interactions and functional homogeneity in biological networks under a pseudo-likelihood parameter estimation approach

    Directory of Open Access Journals (Sweden)

    Luan Yihui

    2009-09-01

    Full Text Available Abstract Background Many aspects of biological functions can be modeled by biological networks, such as protein interaction networks, metabolic networks, and gene coexpression networks. Studying the statistical properties of these networks in turn allows us to infer biological function. Complex statistical network models can potentially more accurately describe the networks, but it is not clear whether such complex models are better suited to find biologically meaningful subnetworks. Results Recent studies have shown that the degree distribution of the nodes is not an adequate statistic in many molecular networks. We sought to extend this statistic with 2nd and 3rd order degree correlations and developed a pseudo-likelihood approach to estimate the parameters. The approach was used to analyze the MIPS and BIOGRID yeast protein interaction networks, and two yeast coexpression networks. We showed that 2nd order degree correlation information gave better predictions of gene interactions in both protein interaction and gene coexpression networks. However, in the biologically important task of predicting functionally homogeneous modules, degree correlation information performs marginally better in the case of the MIPS and BIOGRID protein interaction networks, but worse in the case of gene coexpression networks. Conclusion Our use of dK models showed that incorporation of degree correlations could increase predictive power in some contexts, albeit sometimes marginally, but, in all contexts, the use of third-order degree correlations decreased accuracy. However, it is possible that other parameter estimation methods, such as maximum likelihood, will show the usefulness of incorporating 2nd and 3rd degree correlations in predicting functionally homogeneous modules.

  16. Usefulness and limitations of dK random graph models to predict interactions and functional homogeneity in biological networks under a pseudo-likelihood parameter estimation approach.

    Science.gov (United States)

    Wang, Wenhui; Nunez-Iglesias, Juan; Luan, Yihui; Sun, Fengzhu

    2009-09-03

    Many aspects of biological functions can be modeled by biological networks, such as protein interaction networks, metabolic networks, and gene coexpression networks. Studying the statistical properties of these networks in turn allows us to infer biological function. Complex statistical network models can potentially more accurately describe the networks, but it is not clear whether such complex models are better suited to find biologically meaningful subnetworks. Recent studies have shown that the degree distribution of the nodes is not an adequate statistic in many molecular networks. We sought to extend this statistic with 2nd and 3rd order degree correlations and developed a pseudo-likelihood approach to estimate the parameters. The approach was used to analyze the MIPS and BIOGRID yeast protein interaction networks, and two yeast coexpression networks. We showed that 2nd order degree correlation information gave better predictions of gene interactions in both protein interaction and gene coexpression networks. However, in the biologically important task of predicting functionally homogeneous modules, degree correlation information performs marginally better in the case of the MIPS and BIOGRID protein interaction networks, but worse in the case of gene coexpression networks. Our use of dK models showed that incorporation of degree correlations could increase predictive power in some contexts, albeit sometimes marginally, but, in all contexts, the use of third-order degree correlations decreased accuracy. However, it is possible that other parameter estimation methods, such as maximum likelihood, will show the usefulness of incorporating 2nd and 3rd degree correlations in predicting functionally homogeneous modules.

  17. Network Partitioning Domain Knowledge Multiobjective Application Mapping for Large-Scale Network-on-Chip

    Directory of Open Access Journals (Sweden)

    Yin Zhen Tei

    2014-01-01

    Full Text Available This paper proposes a multiobjective application mapping technique targeted for large-scale network-on-chip (NoC. As the number of intellectual property (IP cores in multiprocessor system-on-chip (MPSoC increases, NoC application mapping to find optimum core-to-topology mapping becomes more challenging. Besides, the conflicting cost and performance trade-off makes multiobjective application mapping techniques even more complex. This paper proposes an application mapping technique that incorporates domain knowledge into genetic algorithm (GA. The initial population of GA is initialized with network partitioning (NP while the crossover operator is guided with knowledge on communication demands. NP reduces the large-scale application mapping complexity and provides GA with a potential mapping search space. The proposed genetic operator is compared with state-of-the-art genetic operators in terms of solution quality. In this work, multiobjective optimization of energy and thermal-balance is considered. Through simulation, knowledge-based initial mapping shows significant improvement in Pareto front compared to random initial mapping that is widely used. The proposed knowledge-based crossover also shows better Pareto front compared to state-of-the-art knowledge-based crossover.

  18. An efficient method based on the uniformity principle for synthesis of large-scale heat exchanger networks

    International Nuclear Information System (INIS)

    Zhang, Chunwei; Cui, Guomin; Chen, Shang

    2016-01-01

    Highlights: • Two dimensionless uniformity factors are presented to heat exchange network. • The grouping of process streams reduces the computational complexity of large-scale HENS problems. • The optimal sub-network can be obtained by Powell particle swarm optimization algorithm. • The method is illustrated by a case study involving 39 process streams, with a better solution. - Abstract: The optimal design of large-scale heat exchanger networks is a difficult task due to the inherent non-linear characteristics and the combinatorial nature of heat exchangers. To solve large-scale heat exchanger network synthesis (HENS) problems, two dimensionless uniformity factors to describe the heat exchanger network (HEN) uniformity in terms of the temperature difference and the accuracy of process stream grouping are deduced. Additionally, a novel algorithm that combines deterministic and stochastic optimizations to obtain an optimal sub-network with a suitable heat load for a given group of streams is proposed, and is named the Powell particle swarm optimization (PPSO). As a result, the synthesis of large-scale heat exchanger networks is divided into two corresponding sub-parts, namely, the grouping of process streams and the optimization of sub-networks. This approach reduces the computational complexity and increases the efficiency of the proposed method. The robustness and effectiveness of the proposed method are demonstrated by solving a large-scale HENS problem involving 39 process streams, and the results obtained are better than those previously published in the literature.

  19. An appraisal of biological responses and network of environmental interactions in non-mining and mining impacted coastal waters

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, C.E.G.; Malik, A; Jineesh, V.K.; Fernandes, S.O.; Das, A; Pandey, S.S.; Kanolkar, G.; Sujith, P.P.; Velip, D.; Shaikh, S.; Helekar, S.; Gonsalves, M.J.B.D.; Nair, S.; LokaBharathi, P.A

    iron brought from the hinterlands. We hypothesize that there could be a shift in biological response along with changes in network of interactions between environmental and biological variables in these mining and non-mining impacted regions, lying 160...

  20. A Brief Introduction to Chinese Biological Biological

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Chinese Biological Abstracts sponsored by the Library, the Shanghai Institutes for Biological Sciences, the Biological Documentation and Information Network, all of the Chinese Academy of Sciences, commenced publication in 1987 and was initiated to provide access to the Chinese information in the field of biology.

  1. Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

    Science.gov (United States)

    Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

    2016-01-01

    Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. © 2015 Wiley Periodicals, Inc.

  2. Recurrent Convolutional Neural Networks: A Better Model of Biological Object Recognition.

    Science.gov (United States)

    Spoerer, Courtney J; McClure, Patrick; Kriegeskorte, Nikolaus

    2017-01-01

    Feedforward neural networks provide the dominant model of how the brain performs visual object recognition. However, these networks lack the lateral and feedback connections, and the resulting recurrent neuronal dynamics, of the ventral visual pathway in the human and non-human primate brain. Here we investigate recurrent convolutional neural networks with bottom-up (B), lateral (L), and top-down (T) connections. Combining these types of connections yields four architectures (B, BT, BL, and BLT), which we systematically test and compare. We hypothesized that recurrent dynamics might improve recognition performance in the challenging scenario of partial occlusion. We introduce two novel occluded object recognition tasks to test the efficacy of the models, digit clutter (where multiple target digits occlude one another) and digit debris (where target digits are occluded by digit fragments). We find that recurrent neural networks outperform feedforward control models (approximately matched in parametric complexity) at recognizing objects, both in the absence of occlusion and in all occlusion conditions. Recurrent networks were also found to be more robust to the inclusion of additive Gaussian noise. Recurrent neural networks are better in two respects: (1) they are more neurobiologically realistic than their feedforward counterparts; (2) they are better in terms of their ability to recognize objects, especially under challenging conditions. This work shows that computer vision can benefit from using recurrent convolutional architectures and suggests that the ubiquitous recurrent connections in biological brains are essential for task performance.

  3. Power-Hop: A Pervasive Observation for Real Complex Networks

    Science.gov (United States)

    2016-03-14

    e.g., power grid, the Internet and the web-graph), social (e.g., friendship networks — Facebook , Gowalla—and co- authorship networks ), urban (e.g...Mislove A., Cha M. and Gummadi K.P. On the evolution of user interaction in Facebook . In Proc. Workshop on Online Social Networks 2009. doi...scale-free distribution is pervasive and describes a large variety of networks , ranging from social and urban to technological and biological networks

  4. Memory Transmission in Small Groups and Large Networks: An Agent-Based Model.

    Science.gov (United States)

    Luhmann, Christian C; Rajaram, Suparna

    2015-12-01

    The spread of social influence in large social networks has long been an interest of social scientists. In the domain of memory, collaborative memory experiments have illuminated cognitive mechanisms that allow information to be transmitted between interacting individuals, but these experiments have focused on small-scale social contexts. In the current study, we took a computational approach, circumventing the practical constraints of laboratory paradigms and providing novel results at scales unreachable by laboratory methodologies. Our model embodied theoretical knowledge derived from small-group experiments and replicated foundational results regarding collaborative inhibition and memory convergence in small groups. Ultimately, we investigated large-scale, realistic social networks and found that agents are influenced by the agents with which they interact, but we also found that agents are influenced by nonneighbors (i.e., the neighbors of their neighbors). The similarity between these results and the reports of behavioral transmission in large networks offers a major theoretical insight by linking behavioral transmission to the spread of information. © The Author(s) 2015.

  5. Multiscale analysis of spreading in a large communication network

    International Nuclear Information System (INIS)

    Kivelä, Mikko; Pan, Raj Kumar; Kaski, Kimmo; Kertész, János; Saramäki, Jari; Karsai, Márton

    2012-01-01

    In temporal networks, both the topology of the underlying network and the timings of interaction events can be crucial in determining how a dynamic process mediated by the network unfolds. We have explored the limiting case of the speed of spreading in the SI model, set up such that an event between an infectious and a susceptible individual always transmits the infection. The speed of this process sets an upper bound for the speed of any dynamic process that is mediated through the interaction events of the network. With the help of temporal networks derived from large-scale time-stamped data on mobile phone calls, we extend earlier results that indicate the slowing-down effects of burstiness and temporal inhomogeneities. In such networks, links are not permanently active, but dynamic processes are mediated by recurrent events taking place on the links at specific points in time. We perform a multiscale analysis and pinpoint the importance of the timings of event sequences on individual links, their correlations with neighboring sequences, and the temporal pathways taken by the network-scale spreading process. This is achieved by studying empirically and analytically different characteristic relay times of links, relevant to the respective scales, and a set of temporal reference models that allow for removing selected time-domain correlations one by one. Our analysis shows that for the spreading velocity, time-domain inhomogeneities are as important as the network topology, which indicates the need to take time-domain information into account when studying spreading dynamics. In particular, results for the different characteristic relay times underline the importance of the burstiness of individual links

  6. A large fiber sensor network for an acoustic neutrino telescope

    Directory of Open Access Journals (Sweden)

    Buis Ernst-Jan

    2017-01-01

    Full Text Available The scientific prospects of detecting neutrinos with an energy close or even higher than the GKZ cut-off energy has been discussed extensively in literature. It is clear that due to their expected low flux, the detection of these ultra-high energy neutrinos (Ev > 1018 eV requires a telescope larger than 100 km3. Acoustic detection may provide a way to observe these ultra-high energy cosmic neutrinos, as sound that they induce in the deep sea when neutrinos lose their energy travels undisturbed for many kilometers. To realize a large scale acoustic neutrino telescope, dedicated technology must be developed that allows for a deep sea sensor network. Fiber optic hydrophone technology provides a promising means to establish a large scale sensor network [1] with the proper sensitivity to detect the small signals from the neutrino interactions.

  7. A Logically Centralized Approach for Control and Management of Large Computer Networks

    Science.gov (United States)

    Iqbal, Hammad A.

    2012-01-01

    Management of large enterprise and Internet service provider networks is a complex, error-prone, and costly challenge. It is widely accepted that the key contributors to this complexity are the bundling of control and data forwarding in traditional routers and the use of fully distributed protocols for network control. To address these…

  8. Connectivity in the yeast cell cycle transcription network: inferences from neural networks.

    Directory of Open Access Journals (Sweden)

    Christopher E Hart

    2006-12-01

    Full Text Available A current challenge is to develop computational approaches to infer gene network regulatory relationships based on multiple types of large-scale functional genomic data. We find that single-layer feed-forward artificial neural network (ANN models can effectively discover gene network structure by integrating global in vivo protein:DNA interaction data (ChIP/Array with genome-wide microarray RNA data. We test this on the yeast cell cycle transcription network, which is composed of several hundred genes with phase-specific RNA outputs. These ANNs were robust to noise in data and to a variety of perturbations. They reliably identified and ranked 10 of 12 known major cell cycle factors at the top of a set of 204, based on a sum-of-squared weights metric. Comparative analysis of motif occurrences among multiple yeast species independently confirmed relationships inferred from ANN weights analysis. ANN models can capitalize on properties of biological gene networks that other kinds of models do not. ANNs naturally take advantage of patterns of absence, as well as presence, of factor binding associated with specific expression output; they are easily subjected to in silico "mutation" to uncover biological redundancies; and they can use the full range of factor binding values. A prominent feature of cell cycle ANNs suggested an analogous property might exist in the biological network. This postulated that "network-local discrimination" occurs when regulatory connections (here between MBF and target genes are explicitly disfavored in one network module (G2, relative to others and to the class of genes outside the mitotic network. If correct, this predicts that MBF motifs will be significantly depleted from the discriminated class and that the discrimination will persist through evolution. Analysis of distantly related Schizosaccharomyces pombe confirmed this, suggesting that network-local discrimination is real and complements well-known enrichment of

  9. Students Mental Representation of Biology Diagrams/Pictures Conventions Based on Formation of Causal Network

    Science.gov (United States)

    Sampurno, A. W.; Rahmat, A.; Diana, S.

    2017-09-01

    Diagrams/pictures conventions is one form of visual media that often used to assist students in understanding the biological concepts. The effectiveness of use diagrams/pictures in biology learning at school level has also been mostly reported. This study examines the ability of high school students in reading diagrams/pictures biological convention which is described by Mental Representation based on formation of causal networks. The study involved 30 students 11th grade MIA senior high school Banten Indonesia who are studying the excretory system. MR data obtained by Instrument worksheet, developed based on CNET-protocol, in which there are diagrams/drawings of nephron structure and urinary mechanism. Three patterns formed MR, namely Markov chain, feedback control with a single measurement, and repeated feedback control with multiple measurement. The third pattern is the most dominating pattern, differences in the pattern of MR reveal the difference in how and from which point the students begin to uncover important information contained in the diagram to establish a causal networks. Further analysis shows that a difference in the pattern of MR relate to how complex the students process the information contained in the diagrams/pictures.

  10. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antczak, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

  11. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    2016-04-01

    Full Text Available The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell

  12. Protein complex prediction in large ontology attributed protein-protein interaction networks.

    Science.gov (United States)

    Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian; Li, Yanpeng; Xu, Bo

    2013-01-01

    Protein complexes are important for unraveling the secrets of cellular organization and function. Many computational approaches have been developed to predict protein complexes in protein-protein interaction (PPI) networks. However, most existing approaches focus mainly on the topological structure of PPI networks, and largely ignore the gene ontology (GO) annotation information. In this paper, we constructed ontology attributed PPI networks with PPI data and GO resource. After constructing ontology attributed networks, we proposed a novel approach called CSO (clustering based on network structure and ontology attribute similarity). Structural information and GO attribute information are complementary in ontology attributed networks. CSO can effectively take advantage of the correlation between frequent GO annotation sets and the dense subgraph for protein complex prediction. Our proposed CSO approach was applied to four different yeast PPI data sets and predicted many well-known protein complexes. The experimental results showed that CSO was valuable in predicting protein complexes and achieved state-of-the-art performance.

  13. Communities in Large Networks: Identification and Ranking

    DEFF Research Database (Denmark)

    Olsen, Martin

    2008-01-01

    We study the problem of identifying and ranking the members of a community in a very large network with link analysis only, given a set of representatives of the community. We define the concept of a community justified by a formal analysis of a simple model of the evolution of a directed graph. ...... and its immediate surroundings. The members are ranked with a “local” variant of the PageRank algorithm. Results are reported from successful experiments on identifying and ranking Danish Computer Science sites and Danish Chess pages using only a few representatives....

  14. Large-Scale Cooperative Task Distribution on Peer-to-Peer Networks

    Science.gov (United States)

    2012-01-01

    SUBTITLE Large-scale cooperative task distribution on peer-to-peer networks 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...disadvantages of ML- Chord are its fixed size (two layers), and limited scala - bility for large-scale systems. RC-Chord extends ML- D. Karrels et al...configurable before runtime. This can be improved by incorporating a distributed learning algorithm to tune the number and range of the DLoE tracking

  15. Modular Neural Tile Architecture for Compact Embedded Hardware Spiking Neural Network

    NARCIS (Netherlands)

    Pande, Sandeep; Morgan, Fearghal; Cawley, Seamus; Bruintjes, Tom; Smit, Gerardus Johannes Maria; McGinley, Brian; Carrillo, Snaider; Harkin, Jim; McDaid, Liam

    2013-01-01

    Biologically-inspired packet switched network on chip (NoC) based hardware spiking neural network (SNN) architectures have been proposed as an embedded computing platform for classification, estimation and control applications. Storage of large synaptic connectivity (SNN topology) information in

  16. Application of hierarchical dissociated neural network in closed-loop hybrid system integrating biological and mechanical intelligence.

    Directory of Open Access Journals (Sweden)

    Yongcheng Li

    Full Text Available Neural networks are considered the origin of intelligence in organisms. In this paper, a new design of an intelligent system merging biological intelligence with artificial intelligence was created. It was based on a neural controller bidirectionally connected to an actual mobile robot to implement a novel vehicle. Two types of experimental preparations were utilized as the neural controller including 'random' and '4Q' (cultured neurons artificially divided into four interconnected parts neural network. Compared to the random cultures, the '4Q' cultures presented absolutely different activities, and the robot controlled by the '4Q' network presented better capabilities in search tasks. Our results showed that neural cultures could be successfully employed to control an artificial agent; the robot performed better and better with the stimulus because of the short-term plasticity. A new framework is provided to investigate the bidirectional biological-artificial interface and develop new strategies for a future intelligent system using these simplified model systems.

  17. Application of Hierarchical Dissociated Neural Network in Closed-Loop Hybrid System Integrating Biological and Mechanical Intelligence

    Science.gov (United States)

    Zhang, Bin; Wang, Yuechao; Li, Hongyi

    2015-01-01

    Neural networks are considered the origin of intelligence in organisms. In this paper, a new design of an intelligent system merging biological intelligence with artificial intelligence was created. It was based on a neural controller bidirectionally connected to an actual mobile robot to implement a novel vehicle. Two types of experimental preparations were utilized as the neural controller including ‘random’ and ‘4Q’ (cultured neurons artificially divided into four interconnected parts) neural network. Compared to the random cultures, the ‘4Q’ cultures presented absolutely different activities, and the robot controlled by the ‘4Q’ network presented better capabilities in search tasks. Our results showed that neural cultures could be successfully employed to control an artificial agent; the robot performed better and better with the stimulus because of the short-term plasticity. A new framework is provided to investigate the bidirectional biological-artificial interface and develop new strategies for a future intelligent system using these simplified model systems. PMID:25992579

  18. Application of hierarchical dissociated neural network in closed-loop hybrid system integrating biological and mechanical intelligence.

    Science.gov (United States)

    Li, Yongcheng; Sun, Rong; Zhang, Bin; Wang, Yuechao; Li, Hongyi

    2015-01-01

    Neural networks are considered the origin of intelligence in organisms. In this paper, a new design of an intelligent system merging biological intelligence with artificial intelligence was created. It was based on a neural controller bidirectionally connected to an actual mobile robot to implement a novel vehicle. Two types of experimental preparations were utilized as the neural controller including 'random' and '4Q' (cultured neurons artificially divided into four interconnected parts) neural network. Compared to the random cultures, the '4Q' cultures presented absolutely different activities, and the robot controlled by the '4Q' network presented better capabilities in search tasks. Our results showed that neural cultures could be successfully employed to control an artificial agent; the robot performed better and better with the stimulus because of the short-term plasticity. A new framework is provided to investigate the bidirectional biological-artificial interface and develop new strategies for a future intelligent system using these simplified model systems.

  19. Towards a Scalable and Adaptive Application Support Platform for Large-Scale Distributed E-Sciences in High-Performance Network Environments

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chase Qishi [New Jersey Inst. of Technology, Newark, NJ (United States); Univ. of Memphis, TN (United States); Zhu, Michelle Mengxia [Southern Illinois Univ., Carbondale, IL (United States)

    2016-06-06

    The advent of large-scale collaborative scientific applications has demonstrated the potential for broad scientific communities to pool globally distributed resources to produce unprecedented data acquisition, movement, and analysis. System resources including supercomputers, data repositories, computing facilities, network infrastructures, storage systems, and display devices have been increasingly deployed at national laboratories and academic institutes. These resources are typically shared by large communities of users over Internet or dedicated networks and hence exhibit an inherent dynamic nature in their availability, accessibility, capacity, and stability. Scientific applications using either experimental facilities or computation-based simulations with various physical, chemical, climatic, and biological models feature diverse scientific workflows as simple as linear pipelines or as complex as a directed acyclic graphs, which must be executed and supported over wide-area networks with massively distributed resources. Application users oftentimes need to manually configure their computing tasks over networks in an ad hoc manner, hence significantly limiting the productivity of scientists and constraining the utilization of resources. The success of these large-scale distributed applications requires a highly adaptive and massively scalable workflow platform that provides automated and optimized computing and networking services. This project is to design and develop a generic Scientific Workflow Automation and Management Platform (SWAMP), which contains a web-based user interface specially tailored for a target application, a set of user libraries, and several easy-to-use computing and networking toolkits for application scientists to conveniently assemble, execute, monitor, and control complex computing workflows in heterogeneous high-performance network environments. SWAMP will enable the automation and management of the entire process of scientific

  20. Community detection using preference networks

    Science.gov (United States)

    Tasgin, Mursel; Bingol, Haluk O.

    2018-04-01

    Community detection is the task of identifying clusters or groups of nodes in a network where nodes within the same group are more connected with each other than with nodes in different groups. It has practical uses in identifying similar functions or roles of nodes in many biological, social and computer networks. With the availability of very large networks in recent years, performance and scalability of community detection algorithms become crucial, i.e. if time complexity of an algorithm is high, it cannot run on large networks. In this paper, we propose a new community detection algorithm, which has a local approach and is able to run on large networks. It has a simple and effective method; given a network, algorithm constructs a preference network of nodes where each node has a single outgoing edge showing its preferred node to be in the same community with. In such a preference network, each connected component is a community. Selection of the preferred node is performed using similarity based metrics of nodes. We use two alternatives for this purpose which can be calculated in 1-neighborhood of nodes, i.e. number of common neighbors of selector node and its neighbors and, the spread capability of neighbors around the selector node which is calculated by the gossip algorithm of Lind et.al. Our algorithm is tested on both computer generated LFR networks and real-life networks with ground-truth community structure. It can identify communities accurately in a fast way. It is local, scalable and suitable for distributed execution on large networks.

  1. An energy-efficient data gathering protocol in large wireless sensor network

    Science.gov (United States)

    Wang, Yamin; Zhang, Ruihua; Tao, Shizhong

    2006-11-01

    Wireless sensor network consisting of a large number of small sensors with low-power transceiver can be an effective tool for gathering data in a variety of environment. The collected data must be transmitted to the base station for further processing. Since a network consists of sensors with limited battery energy, the method for data gathering and routing must be energy efficient in order to prolong the lifetime of the network. In this paper, we presented an energy-efficient data gathering protocol in wireless sensor network. The new protocol used data fusion technology clusters nodes into groups and builds a chain among the cluster heads according to a hybrid of the residual energy and distance to the base station. Results in stochastic geometry are used to derive the optimum parameter of our algorithm that minimizes the total energy spent in the network. Simulation results show performance superiority of the new protocol.

  2. A Non-Homogeneous Dynamic Bayesian Network with Sequentially Coupled Interaction Parameters for Applications in Systems and Synthetic Biology

    NARCIS (Netherlands)

    Grzegorczyk, Marco; Husmeier, Dirk

    2012-01-01

    An important and challenging problem in systems biology is the inference of gene regulatory networks from short non-stationary time series of transcriptional profiles. A popular approach that has been widely applied to this end is based on dynamic Bayesian networks (DBNs), although traditional

  3. Parameter estimation in large-scale systems biology models: a parallel and self-adaptive cooperative strategy.

    Science.gov (United States)

    Penas, David R; González, Patricia; Egea, Jose A; Doallo, Ramón; Banga, Julio R

    2017-01-21

    The development of large-scale kinetic models is one of the current key issues in computational systems biology and bioinformatics. Here we consider the problem of parameter estimation in nonlinear dynamic models. Global optimization methods can be used to solve this type of problems but the associated computational cost is very large. Moreover, many of these methods need the tuning of a number of adjustable search parameters, requiring a number of initial exploratory runs and therefore further increasing the computation times. Here we present a novel parallel method, self-adaptive cooperative enhanced scatter search (saCeSS), to accelerate the solution of this class of problems. The method is based on the scatter search optimization metaheuristic and incorporates several key new mechanisms: (i) asynchronous cooperation between parallel processes, (ii) coarse and fine-grained parallelism, and (iii) self-tuning strategies. The performance and robustness of saCeSS is illustrated by solving a set of challenging parameter estimation problems, including medium and large-scale kinetic models of the bacterium E. coli, bakerés yeast S. cerevisiae, the vinegar fly D. melanogaster, Chinese Hamster Ovary cells, and a generic signal transduction network. The results consistently show that saCeSS is a robust and efficient method, allowing very significant reduction of computation times with respect to several previous state of the art methods (from days to minutes, in several cases) even when only a small number of processors is used. The new parallel cooperative method presented here allows the solution of medium and large scale parameter estimation problems in reasonable computation times and with small hardware requirements. Further, the method includes self-tuning mechanisms which facilitate its use by non-experts. We believe that this new method can play a key role in the development of large-scale and even whole-cell dynamic models.

  4. Procurement of a Large Area Mapping FTIR Microscope for Organic-Inorganic Interfacial Analysis in Biological Materials

    Science.gov (United States)

    2015-12-31

    SECURITY CLASSIFICATION OF: After acquiring the Infrared Imaging Microscope with large area mapping capabilities for structure -function research and...Inorganic Interfacial Analysis in Biological Materials The views, opinions and/or findings contained in this report are those of the author(s) and should...of a Large Area Mapping FTIR Microscope for Organic-Inorganic Interfacial Analysis in Biological Materials Report Title After acquiring the Infrared

  5. Half dozen of one, six billion of the other: What can small- and large-scale molecular systems biology learn from one another?

    Science.gov (United States)

    Mellis, Ian A; Raj, Arjun

    2015-10-01

    Small-scale molecular systems biology, by which we mean the understanding of a how a few parts work together to control a particular biological process, is predicated on the assumption that cellular regulation is arranged in a circuit-like structure. Results from the omics revolution have upset this vision to varying degrees by revealing a high degree of interconnectivity, making it difficult to develop a simple, circuit-like understanding of regulatory processes. We here outline the limitations of the small-scale systems biology approach with examples from research into genetic algorithms, genetics, transcriptional network analysis, and genomics. We also discuss the difficulties associated with deriving true understanding from the analysis of large data sets and propose that the development of new, intelligent, computational tools may point to a way forward. Throughout, we intentionally oversimplify and talk about things in which we have little expertise, and it is likely that many of our arguments are wrong on one level or another. We do believe, however, that developing a true understanding via molecular systems biology will require a fundamental rethinking of our approach, and our goal is to provoke thought along these lines. © 2015 Mellis and Raj; Published by Cold Spring Harbor Laboratory Press.

  6. A review of active learning approaches to experimental design for uncovering biological networks

    Science.gov (United States)

    2017-01-01

    Various types of biological knowledge describe networks of interactions among elementary entities. For example, transcriptional regulatory networks consist of interactions among proteins and genes. Current knowledge about the exact structure of such networks is highly incomplete, and laboratory experiments that manipulate the entities involved are conducted to test hypotheses about these networks. In recent years, various automated approaches to experiment selection have been proposed. Many of these approaches can be characterized as active machine learning algorithms. Active learning is an iterative process in which a model is learned from data, hypotheses are generated from the model to propose informative experiments, and the experiments yield new data that is used to update the model. This review describes the various models, experiment selection strategies, validation techniques, and successful applications described in the literature; highlights common themes and notable distinctions among methods; and identifies likely directions of future research and open problems in the area. PMID:28570593

  7. In silico model-based inference: a contemporary approach for hypothesis testing in network biology.

    Science.gov (United States)

    Klinke, David J

    2014-01-01

    Inductive inference plays a central role in the study of biological systems where one aims to increase their understanding of the system by reasoning backwards from uncertain observations to identify causal relationships among components of the system. These causal relationships are postulated from prior knowledge as a hypothesis or simply a model. Experiments are designed to test the model. Inferential statistics are used to establish a level of confidence in how well our postulated model explains the acquired data. This iterative process, commonly referred to as the scientific method, either improves our confidence in a model or suggests that we revisit our prior knowledge to develop a new model. Advances in technology impact how we use prior knowledge and data to formulate models of biological networks and how we observe cellular behavior. However, the approach for model-based inference has remained largely unchanged since Fisher, Neyman and Pearson developed the ideas in the early 1900s that gave rise to what is now known as classical statistical hypothesis (model) testing. Here, I will summarize conventional methods for model-based inference and suggest a contemporary approach to aid in our quest to discover how cells dynamically interpret and transmit information for therapeutic aims that integrates ideas drawn from high performance computing, Bayesian statistics, and chemical kinetics. © 2014 American Institute of Chemical Engineers.

  8. Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually relevant hubs in biological networks.

    Science.gov (United States)

    Muetze, Tanja; Goenawan, Ivan H; Wiencko, Heather L; Bernal-Llinares, Manuel; Bryan, Kenneth; Lynn, David J

    2016-01-01

    Highly connected nodes (hubs) in biological networks are topologically important to the structure of the network and have also been shown to be preferentially associated with a range of phenotypes of interest. The relative importance of a hub node, however, can change depending on the biological context. Here, we report a Cytoscape app, the Contextual Hub Analysis Tool (CHAT), which enables users to easily construct and visualize a network of interactions from a gene or protein list of interest, integrate contextual information, such as gene expression or mass spectrometry data, and identify hub nodes that are more highly connected to contextual nodes (e.g. genes or proteins that are differentially expressed) than expected by chance. In a case study, we use CHAT to construct a network of genes that are differentially expressed in Dengue fever, a viral infection. CHAT was used to identify and compare contextual and degree-based hubs in this network. The top 20 degree-based hubs were enriched in pathways related to the cell cycle and cancer, which is likely due to the fact that proteins involved in these processes tend to be highly connected in general. In comparison, the top 20 contextual hubs were enriched in pathways commonly observed in a viral infection including pathways related to the immune response to viral infection. This analysis shows that such contextual hubs are considerably more biologically relevant than degree-based hubs and that analyses which rely on the identification of hubs solely based on their connectivity may be biased towards nodes that are highly connected in general rather than in the specific context of interest. CHAT is available for Cytoscape 3.0+ and can be installed via the Cytoscape App Store ( http://apps.cytoscape.org/apps/chat).

  9. Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.

    Science.gov (United States)

    Yu, Bowen; Doraiswamy, Harish; Chen, Xi; Miraldi, Emily; Arrieta-Ortiz, Mario Luis; Hafemeister, Christoph; Madar, Aviv; Bonneau, Richard; Silva, Cláudio T

    2014-12-01

    Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).

  10. Extracting reaction networks from databases-opening Pandora's box.

    Science.gov (United States)

    Fearnley, Liam G; Davis, Melissa J; Ragan, Mark A; Nielsen, Lars K

    2014-11-01

    Large quantities of information describing the mechanisms of biological pathways continue to be collected in publicly available databases. At the same time, experiments have increased in scale, and biologists increasingly use pathways defined in online databases to interpret the results of experiments and generate hypotheses. Emerging computational techniques that exploit the rich biological information captured in reaction systems require formal standardized descriptions of pathways to extract these reaction networks and avoid the alternative: time-consuming and largely manual literature-based network reconstruction. Here, we systematically evaluate the effects of commonly used knowledge representations on the seemingly simple task of extracting a reaction network describing signal transduction from a pathway database. We show that this process is in fact surprisingly difficult, and the pathway representations adopted by various knowledge bases have dramatic consequences for reaction network extraction, connectivity, capture of pathway crosstalk and in the modelling of cell-cell interactions. Researchers constructing computational models built from automatically extracted reaction networks must therefore consider the issues we outline in this review to maximize the value of existing pathway knowledge. © The Author 2013. Published by Oxford University Press.

  11. Qualitative reasoning for biological network inference from systematic perturbation experiments.

    Science.gov (United States)

    Badaloni, Silvana; Di Camillo, Barbara; Sambo, Francesco

    2012-01-01

    The systematic perturbation of the components of a biological system has been proven among the most informative experimental setups for the identification of causal relations between the components. In this paper, we present Systematic Perturbation-Qualitative Reasoning (SPQR), a novel Qualitative Reasoning approach to automate the interpretation of the results of systematic perturbation experiments. Our method is based on a qualitative abstraction of the experimental data: for each perturbation experiment, measured values of the observed variables are modeled as lower, equal or higher than the measurements in the wild type condition, when no perturbation is applied. The algorithm exploits a set of IF-THEN rules to infer causal relations between the variables, analyzing the patterns of propagation of the perturbation signals through the biological network, and is specifically designed to minimize the rate of false positives among the inferred relations. Tested on both simulated and real perturbation data, SPQR indeed exhibits a significantly higher precision than the state of the art.

  12. Large-scale transportation network congestion evolution prediction using deep learning theory.

    Science.gov (United States)

    Ma, Xiaolei; Yu, Haiyang; Wang, Yunpeng; Wang, Yinhai

    2015-01-01

    Understanding how congestion at one location can cause ripples throughout large-scale transportation network is vital for transportation researchers and practitioners to pinpoint traffic bottlenecks for congestion mitigation. Traditional studies rely on either mathematical equations or simulation techniques to model traffic congestion dynamics. However, most of the approaches have limitations, largely due to unrealistic assumptions and cumbersome parameter calibration process. With the development of Intelligent Transportation Systems (ITS) and Internet of Things (IoT), transportation data become more and more ubiquitous. This triggers a series of data-driven research to investigate transportation phenomena. Among them, deep learning theory is considered one of the most promising techniques to tackle tremendous high-dimensional data. This study attempts to extend deep learning theory into large-scale transportation network analysis. A deep Restricted Boltzmann Machine and Recurrent Neural Network architecture is utilized to model and predict traffic congestion evolution based on Global Positioning System (GPS) data from taxi. A numerical study in Ningbo, China is conducted to validate the effectiveness and efficiency of the proposed method. Results show that the prediction accuracy can achieve as high as 88% within less than 6 minutes when the model is implemented in a Graphic Processing Unit (GPU)-based parallel computing environment. The predicted congestion evolution patterns can be visualized temporally and spatially through a map-based platform to identify the vulnerable links for proactive congestion mitigation.

  13. Thermodynamically based constraints for rate coefficients of large biochemical networks.

    Science.gov (United States)

    Vlad, Marcel O; Ross, John

    2009-01-01

    Wegscheider cyclicity conditions are relationships among the rate coefficients of a complex reaction network, which ensure the compatibility of kinetic equations with the conditions for thermodynamic equilibrium. The detailed balance at equilibrium, that is the equilibration of forward and backward rates for each elementary reaction, leads to compatibility between the conditions of kinetic and thermodynamic equilibrium. Therefore, Wegscheider cyclicity conditions can be derived by eliminating the equilibrium concentrations from the conditions of detailed balance. We develop matrix algebra tools needed to carry out this elimination, reexamine an old derivation of the general form of Wegscheider cyclicity condition, and develop new derivations which lead to more compact and easier-to-use formulas. We derive scaling laws for the nonequilibrium rates of a complex reaction network, which include Wegscheider conditions as a particular case. The scaling laws for the rates are used for clarifying the kinetic and thermodynamic meaning of Wegscheider cyclicity conditions. Finally, we discuss different ways of using Wegscheider cyclicity conditions for kinetic computations in systems biology.

  14. Output regulation of large-scale hydraulic networks with minimal steady state power consumption

    NARCIS (Netherlands)

    Jensen, Tom Nørgaard; Wisniewski, Rafał; De Persis, Claudio; Kallesøe, Carsten Skovmose

    2014-01-01

    An industrial case study involving a large-scale hydraulic network is examined. The hydraulic network underlies a district heating system, with an arbitrary number of end-users. The problem of output regulation is addressed along with a optimization criterion for the control. The fact that the

  15. Fast and accurate detection of spread source in large complex networks.

    Science.gov (United States)

    Paluch, Robert; Lu, Xiaoyan; Suchecki, Krzysztof; Szymański, Bolesław K; Hołyst, Janusz A

    2018-02-06

    Spread over complex networks is a ubiquitous process with increasingly wide applications. Locating spread sources is often important, e.g. finding the patient one in epidemics, or source of rumor spreading in social network. Pinto, Thiran and Vetterli introduced an algorithm (PTVA) to solve the important case of this problem in which a limited set of nodes act as observers and report times at which the spread reached them. PTVA uses all observers to find a solution. Here we propose a new approach in which observers with low quality information (i.e. with large spread encounter times) are ignored and potential sources are selected based on the likelihood gradient from high quality observers. The original complexity of PTVA is O(N α ), where α ∈ (3,4) depends on the network topology and number of observers (N denotes the number of nodes in the network). Our Gradient Maximum Likelihood Algorithm (GMLA) reduces this complexity to O (N 2 log (N)). Extensive numerical tests performed on synthetic networks and real Gnutella network with limitation that id's of spreaders are unknown to observers demonstrate that for scale-free networks with such limitation GMLA yields higher quality localization results than PTVA does.

  16. Rapid Modeling of and Response to Large Earthquakes Using Real-Time GPS Networks (Invited)

    Science.gov (United States)

    Crowell, B. W.; Bock, Y.; Squibb, M. B.

    2010-12-01

    Real-time GPS networks have the advantage of capturing motions throughout the entire earthquake cycle (interseismic, seismic, coseismic, postseismic), and because of this, are ideal for real-time monitoring of fault slip in the region. Real-time GPS networks provide the perfect supplement to seismic networks, which operate with lower noise and higher sampling rates than GPS networks, but only measure accelerations or velocities, putting them at a supreme disadvantage for ascertaining the full extent of slip during a large earthquake in real-time. Here we report on two examples of rapid modeling of recent large earthquakes near large regional real-time GPS networks. The first utilizes Japan’s GEONET consisting of about 1200 stations during the 2003 Mw 8.3 Tokachi-Oki earthquake about 100 km offshore Hokkaido Island and the second investigates the 2010 Mw 7.2 El Mayor-Cucapah earthquake recorded by more than 100 stations in the California Real Time Network. The principal components of strain were computed throughout the networks and utilized as a trigger to initiate earthquake modeling. Total displacement waveforms were then computed in a simulated real-time fashion using a real-time network adjustment algorithm that fixes a station far away from the rupture to obtain a stable reference frame. Initial peak ground displacement measurements can then be used to obtain an initial size through scaling relationships. Finally, a full coseismic model of the event can be run minutes after the event, given predefined fault geometries, allowing emergency first responders and researchers to pinpoint the regions of highest damage. Furthermore, we are also investigating using total displacement waveforms for real-time moment tensor inversions to look at spatiotemporal variations in slip.

  17. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering. PMID:24709875

  18. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

    Full Text Available Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  19. Consistent robustness analysis (CRA) identifies biologically relevant properties of regulatory network models.

    Science.gov (United States)

    Saithong, Treenut; Painter, Kevin J; Millar, Andrew J

    2010-12-16

    A number of studies have previously demonstrated that "goodness of fit" is insufficient in reliably classifying the credibility of a biological model. Robustness and/or sensitivity analysis is commonly employed as a secondary method for evaluating the suitability of a particular model. The results of such analyses invariably depend on the particular parameter set tested, yet many parameter values for biological models are uncertain. Here, we propose a novel robustness analysis that aims to determine the "common robustness" of the model with multiple, biologically plausible parameter sets, rather than the local robustness for a particular parameter set. Our method is applied to two published models of the Arabidopsis circadian clock (the one-loop [1] and two-loop [2] models). The results reinforce current findings suggesting the greater reliability of the two-loop model and pinpoint the crucial role of TOC1 in the circadian network. Consistent Robustness Analysis can indicate both the relative plausibility of different models and also the critical components and processes controlling each model.

  20. A Parallel Supercomputer Implementation of a Biological Inspired Neural Network and its use for Pattern Recognition

    International Nuclear Information System (INIS)

    De Ladurantaye, Vincent; Lavoie, Jean; Bergeron, Jocelyn; Parenteau, Maxime; Lu Huizhong; Pichevar, Ramin; Rouat, Jean

    2012-01-01

    A parallel implementation of a large spiking neural network is proposed and evaluated. The neural network implements the binding by synchrony process using the Oscillatory Dynamic Link Matcher (ODLM). Scalability, speed and performance are compared for 2 implementations: Message Passing Interface (MPI) and Compute Unified Device Architecture (CUDA) running on clusters of multicore supercomputers and NVIDIA graphical processing units respectively. A global spiking list that represents at each instant the state of the neural network is described. This list indexes each neuron that fires during the current simulation time so that the influence of their spikes are simultaneously processed on all computing units. Our implementation shows a good scalability for very large networks. A complex and large spiking neural network has been implemented in parallel with success, thus paving the road towards real-life applications based on networks of spiking neurons. MPI offers a better scalability than CUDA, while the CUDA implementation on a GeForce GTX 285 gives the best cost to performance ratio. When running the neural network on the GTX 285, the processing speed is comparable to the MPI implementation on RQCHP's Mammouth parallel with 64 notes (128 cores).

  1. Biological neural networks as model systems for designing future parallel processing computers

    Science.gov (United States)

    Ross, Muriel D.

    1991-01-01

    One of the more interesting debates of the present day centers on whether human intelligence can be simulated by computer. The author works under the premise that neurons individually are not smart at all. Rather, they are physical units which are impinged upon continuously by other matter that influences the direction of voltage shifts across the units membranes. It is only the action of a great many neurons, billions in the case of the human nervous system, that intelligent behavior emerges. What is required to understand even the simplest neural system is painstaking analysis, bit by bit, of the architecture and the physiological functioning of its various parts. The biological neural network studied, the vestibular utricular and saccular maculas of the inner ear, are among the most simple of the mammalian neural networks to understand and model. While there is still a long way to go to understand even this most simple neural network in sufficient detail for extrapolation to computers and robots, a start was made. Moreover, the insights obtained and the technologies developed help advance the understanding of the more complex neural networks that underlie human intelligence.

  2. Tradeoffs between quality-of-control and quality-of-service in large-scale nonlinear networked control systems

    NARCIS (Netherlands)

    Borgers, D. P.; Geiselhart, R.; Heemels, W. P. M. H.

    2017-01-01

    In this paper we study input-to-state stability (ISS) of large-scale networked control systems (NCSs) in which sensors, controllers and actuators are connected via multiple (local) communication networks which operate asynchronously and independently of each other. We model the large-scale NCS as an

  3. A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology

    NARCIS (Netherlands)

    Herrgård, Markus J.; Swainston, Neil; Dobson, Paul; Dunn, Warwick B.; Arga, K. Yalçin; Arvas, Mikko; Blüthgen, Nils; Borger, Simon; Costenoble, Roeland; Heinemann, Matthias; Hucka, Michael; Novère, Nicolas Le; Li, Peter; Liebermeister, Wolfram; Mo, Monica L.; Oliveira, Ana Paula; Petranovic, Dina; Pettifer, Stephen; Simeonidis, Evangelos; Smallbone, Kieran; Spasić, Irena; Weichart, Dieter; Brent, Roger; Broomhead, David S.; Westerhoff, Hans V.; Kırdar, Betül; Penttilä, Merja; Klipp, Edda; Palsson, Bernhard Ø.; Sauer, Uwe; Oliver, Stephen G.; Mendes, Pedro; Nielsen, Jens; Kell, Douglas B.

    2008-01-01

    Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several genome-scale network reconstructions describe Saccharomyces cerevisiae metabolism, they differ in scope and

  4. Equation Chapter 1 Section 1Cross Layer Design for Localization in Large-Scale Underwater Sensor Networks

    Directory of Open Access Journals (Sweden)

    Yuanfeng ZHANG

    2014-02-01

    Full Text Available There are many technical challenges for designing large-scale underwater sensor networks, especially the sensor node localization. Although many papers studied for large-scale sensor node localization, previous studies mainly study the location algorithm without the cross layer design for localization. In this paper, by utilizing the network hierarchical structure of underwater sensor networks, we propose a new large-scale underwater acoustic localization scheme based on cross layer design. In this scheme, localization is performed in a hierarchical way, and the whole localization process focused on the physical layer, data link layer and application layer. We increase the pipeline parameters which matched the acoustic channel, added in MAC protocol to increase the authenticity of the large-scale underwater sensor networks, and made analysis of different location algorithm. We conduct extensive simulations, and our results show that MAC layer protocol and the localization algorithm all would affect the result of localization which can balance the trade-off between localization accuracy, localization coverage, and communication cost.

  5. Inferring the conservative causal core of gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Emmert-Streib Frank

    2010-09-01

    Full Text Available Abstract Background Inferring gene regulatory networks from large-scale expression data is an important problem that received much attention in recent years. These networks have the potential to gain insights into causal molecular interactions of biological processes. Hence, from a methodological point of view, reliable estimation methods based on observational data are needed to approach this problem practically. Results In this paper, we introduce a novel gene regulatory network inference (GRNI algorithm, called C3NET. We compare C3NET with four well known methods, ARACNE, CLR, MRNET and RN, conducting in-depth numerical ensemble simulations and demonstrate also for biological expression data from E. coli that C3NET performs consistently better than the best known GRNI methods in the literature. In addition, it has also a low computational complexity. Since C3NET is based on estimates of mutual information values in conjunction with a maximization step, our numerical investigations demonstrate that our inference algorithm exploits causal structural information in the data efficiently. Conclusions For systems biology to succeed in the long run, it is of crucial importance to establish methods that extract large-scale gene networks from high-throughput data that reflect the underlying causal interactions among genes or gene products. Our method can contribute to this endeavor by demonstrating that an inference algorithm with a neat design permits not only a more intuitive and possibly biological interpretation of its working mechanism but can also result in superior results.

  6. Inferring the conservative causal core of gene regulatory networks.

    Science.gov (United States)

    Altay, Gökmen; Emmert-Streib, Frank

    2010-09-28

    Inferring gene regulatory networks from large-scale expression data is an important problem that received much attention in recent years. These networks have the potential to gain insights into causal molecular interactions of biological processes. Hence, from a methodological point of view, reliable estimation methods based on observational data are needed to approach this problem practically. In this paper, we introduce a novel gene regulatory network inference (GRNI) algorithm, called C3NET. We compare C3NET with four well known methods, ARACNE, CLR, MRNET and RN, conducting in-depth numerical ensemble simulations and demonstrate also for biological expression data from E. coli that C3NET performs consistently better than the best known GRNI methods in the literature. In addition, it has also a low computational complexity. Since C3NET is based on estimates of mutual information values in conjunction with a maximization step, our numerical investigations demonstrate that our inference algorithm exploits causal structural information in the data efficiently. For systems biology to succeed in the long run, it is of crucial importance to establish methods that extract large-scale gene networks from high-throughput data that reflect the underlying causal interactions among genes or gene products. Our method can contribute to this endeavor by demonstrating that an inference algorithm with a neat design permits not only a more intuitive and possibly biological interpretation of its working mechanism but can also result in superior results.

  7. Cell cycle gene expression networks discovered using systems biology: Significance in carcinogenesis

    Science.gov (United States)

    Scott, RE; Ghule, PN; Stein, JL; Stein, GS

    2015-01-01

    The early stages of carcinogenesis are linked to defects in the cell cycle. A series of cell cycle checkpoints are involved in this process. The G1/S checkpoint that serves to integrate the control of cell proliferation and differentiation is linked to carcinogenesis and the mitotic spindle checkpoint with the development of chromosomal instability. This paper presents the outcome of systems biology studies designed to evaluate if networks of covariate cell cycle gene transcripts exist in proliferative mammalian tissues including mice, rats and humans. The GeneNetwork website that contains numerous gene expression datasets from different species, sexes and tissues represents the foundational resource for these studies (www.genenetwork.org). In addition, WebGestalt, a gene ontology tool, facilitated the identification of expression networks of genes that co-vary with key cell cycle targets, especially Cdc20 and Plk1 (www.bioinfo.vanderbilt.edu/webgestalt). Cell cycle expression networks of such covariate mRNAs exist in multiple proliferative tissues including liver, lung, pituitary, adipose and lymphoid tissues among others but not in brain or retina that have low proliferative potential. Sixty-three covariate cell cycle gene transcripts (mRNAs) compose the average cell cycle network with p = e−13 to e−36. Cell cycle expression networks show species, sex and tissue variability and they are enriched in mRNA transcripts associated with mitosis many of which are associated with chromosomal instability. PMID:25808367

  8. A balanced memory network.

    Directory of Open Access Journals (Sweden)

    Yasser Roudi

    2007-09-01

    Full Text Available A fundamental problem in neuroscience is understanding how working memory--the ability to store information at intermediate timescales, like tens of seconds--is implemented in realistic neuronal networks. The most likely candidate mechanism is the attractor network, and a great deal of effort has gone toward investigating it theoretically. Yet, despite almost a quarter century of intense work, attractor networks are not fully understood. In particular, there are still two unanswered questions. First, how is it that attractor networks exhibit irregular firing, as is observed experimentally during working memory tasks? And second, how many memories can be stored under biologically realistic conditions? Here we answer both questions by studying an attractor neural network in which inhibition and excitation balance each other. Using mean-field analysis, we derive a three-variable description of attractor networks. From this description it follows that irregular firing can exist only if the number of neurons involved in a memory is large. The same mean-field analysis also shows that the number of memories that can be stored in a network scales with the number of excitatory connections, a result that has been suggested for simple models but never shown for realistic ones. Both of these predictions are verified using simulations with large networks of spiking neurons.

  9. Socio-Cognitive Phenotypes Differentially Modulate Large-Scale Structural Covariance Networks.

    Science.gov (United States)

    Valk, Sofie L; Bernhardt, Boris C; Böckler, Anne; Trautwein, Fynn-Mathis; Kanske, Philipp; Singer, Tania

    2017-02-01

    Functional neuroimaging studies have suggested the existence of 2 largely distinct social cognition networks, one for theory of mind (taking others' cognitive perspective) and another for empathy (sharing others' affective states). To address whether these networks can also be dissociated at the level of brain structure, we combined behavioral phenotyping across multiple socio-cognitive tasks with 3-Tesla MRI cortical thickness and structural covariance analysis in 270 healthy adults, recruited across 2 sites. Regional thickness mapping only provided partial support for divergent substrates, highlighting that individual differences in empathy relate to left insular-opercular thickness while no correlation between thickness and mentalizing scores was found. Conversely, structural covariance analysis showed clearly divergent network modulations by socio-cognitive and -affective phenotypes. Specifically, individual differences in theory of mind related to structural integration between temporo-parietal and dorsomedial prefrontal regions while empathy modulated the strength of dorsal anterior insula networks. Findings were robust across both recruitment sites, suggesting generalizability. At the level of structural network embedding, our study provides a double dissociation between empathy and mentalizing. Moreover, our findings suggest that structural substrates of higher-order social cognition are reflected rather in interregional networks than in the the local anatomical markup of specific regions per se. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Empirical Models of Social Learning in a Large, Evolving Network.

    Directory of Open Access Journals (Sweden)

    Ayşe Başar Bener

    Full Text Available This paper advances theories of social learning through an empirical examination of how social networks change over time. Social networks are important for learning because they constrain individuals' access to information about the behaviors and cognitions of other people. Using data on a large social network of mobile device users over a one-month time period, we test three hypotheses: 1 attraction homophily causes individuals to form ties on the basis of attribute similarity, 2 aversion homophily causes individuals to delete existing ties on the basis of attribute dissimilarity, and 3 social influence causes individuals to adopt the attributes of others they share direct ties with. Statistical models offer varied degrees of support for all three hypotheses and show that these mechanisms are more complex than assumed in prior work. Although homophily is normally thought of as a process of attraction, people also avoid relationships with others who are different. These mechanisms have distinct effects on network structure. While social influence does help explain behavior, people tend to follow global trends more than they follow their friends.

  11. Cardinality Estimation Algorithm in Large-Scale Anonymous Wireless Sensor Networks

    KAUST Repository

    Douik, Ahmed

    2017-08-30

    Consider a large-scale anonymous wireless sensor network with unknown cardinality. In such graphs, each node has no information about the network topology and only possesses a unique identifier. This paper introduces a novel distributed algorithm for cardinality estimation and topology discovery, i.e., estimating the number of node and structure of the graph, by querying a small number of nodes and performing statistical inference methods. While the cardinality estimation allows the design of more efficient coding schemes for the network, the topology discovery provides a reliable way for routing packets. The proposed algorithm is shown to produce a cardinality estimate proportional to the best linear unbiased estimator for dense graphs and specific running times. Simulation results attest the theoretical results and reveal that, for a reasonable running time, querying a small group of nodes is sufficient to perform an estimation of 95% of the whole network. Applications of this work include estimating the number of Internet of Things (IoT) sensor devices, online social users, active protein cells, etc.

  12. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine

    International Nuclear Information System (INIS)

    Stites, Edward C

    2013-01-01

    Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients. (paper)

  13. Large deep neural networks for MS lesion segmentation

    Science.gov (United States)

    Prieto, Juan C.; Cavallari, Michele; Palotai, Miklos; Morales Pinzon, Alfredo; Egorova, Svetlana; Styner, Martin; Guttmann, Charles R. G.

    2017-02-01

    Multiple sclerosis (MS) is a multi-factorial autoimmune disorder, characterized by spatial and temporal dissemination of brain lesions that are visible in T2-weighted and Proton Density (PD) MRI. Assessment of lesion burden and is useful for monitoring the course of the disease, and assessing correlates of clinical outcomes. Although there are established semi-automated methods to measure lesion volume, most of them require human interaction and editing, which are time consuming and limits the ability to analyze large sets of data with high accuracy. The primary objective of this work is to improve existing segmentation algorithms and accelerate the time consuming operation of identifying and validating MS lesions. In this paper, a Deep Neural Network for MS Lesion Segmentation is implemented. The MS lesion samples are extracted from the Partners Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) study. A set of 900 subjects with T2, PD and a manually corrected label map images were used to train a Deep Neural Network and identify MS lesions. Initial tests using this network achieved a 90% accuracy rate. A secondary goal was to enable this data repository for big data analysis by using this algorithm to segment the remaining cases available in the CLIMB repository.

  14. Integrating large-scale functional genomics data to dissect metabolic networks for hydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Harwood, Caroline S

    2012-12-17

    The goal of this project is to identify gene networks that are critical for efficient biohydrogen production by leveraging variation in gene content and gene expression in independently isolated Rhodopseudomonas palustris strains. Coexpression methods were applied to large data sets that we have collected to define probabilistic causal gene networks. To our knowledge this a first systems level approach that takes advantage of strain-to strain variability to computationally define networks critical for a particular bacterial phenotypic trait.

  15. Exploring candidate biological functions by Boolean Function Networks for Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Maria Simak

    Full Text Available The great amount of gene expression data has brought a big challenge for the discovery of Gene Regulatory Network (GRN. For network reconstruction and the investigation of regulatory relations, it is desirable to ensure directness of links between genes on a map, infer their directionality and explore candidate biological functions from high-throughput transcriptomic data. To address these problems, we introduce a Boolean Function Network (BFN model based on techniques of hidden Markov model (HMM, likelihood ratio test and Boolean logic functions. BFN consists of two consecutive tests to establish links between pairs of genes and check their directness. We evaluate the performance of BFN through the application to S. cerevisiae time course data. BFN produces regulatory relations which show consistency with succession of cell cycle phases. Furthermore, it also improves sensitivity and specificity when compared with alternative methods of genetic network reverse engineering. Moreover, we demonstrate that BFN can provide proper resolution for GO enrichment of gene sets. Finally, the Boolean functions discovered by BFN can provide useful insights for the identification of control mechanisms of regulatory processes, which is the special advantage of the proposed approach. In combination with low computational complexity, BFN can serve as an efficient screening tool to reconstruct genes relations on the whole genome level. In addition, the BFN approach is also feasible to a wide range of time course datasets.

  16. Large-scale transportation network congestion evolution prediction using deep learning theory.

    Directory of Open Access Journals (Sweden)

    Xiaolei Ma

    Full Text Available Understanding how congestion at one location can cause ripples throughout large-scale transportation network is vital for transportation researchers and practitioners to pinpoint traffic bottlenecks for congestion mitigation. Traditional studies rely on either mathematical equations or simulation techniques to model traffic congestion dynamics. However, most of the approaches have limitations, largely due to unrealistic assumptions and cumbersome parameter calibration process. With the development of Intelligent Transportation Systems (ITS and Internet of Things (IoT, transportation data become more and more ubiquitous. This triggers a series of data-driven research to investigate transportation phenomena. Among them, deep learning theory is considered one of the most promising techniques to tackle tremendous high-dimensional data. This study attempts to extend deep learning theory into large-scale transportation network analysis. A deep Restricted Boltzmann Machine and Recurrent Neural Network architecture is utilized to model and predict traffic congestion evolution based on Global Positioning System (GPS data from taxi. A numerical study in Ningbo, China is conducted to validate the effectiveness and efficiency of the proposed method. Results show that the prediction accuracy can achieve as high as 88% within less than 6 minutes when the model is implemented in a Graphic Processing Unit (GPU-based parallel computing environment. The predicted congestion evolution patterns can be visualized temporally and spatially through a map-based platform to identify the vulnerable links for proactive congestion mitigation.

  17. Standard and biological treatment in large vessel vasculitis: guidelines and current approaches.

    Science.gov (United States)

    Muratore, Francesco; Pipitone, Nicolò; Salvarani, Carlo

    2017-04-01

    Giant cell arteritis and Takayasu arteritis are the two major forms of idiopathic large vessel vasculitis. High doses of glucocorticoids are effective in inducing remission in both conditions, but relapses and recurrences are common, requiring prolonged glucocorticoid treatment with the risk of the related adverse events. Areas covered: In this article, we will review the standard and biological treatment strategies in large vessel vasculitis, and we will focus on the current approaches to these diseases. Expert commentary: The results of treatment trials with conventional immunosuppressive agents such as methotrexate, azathioprine, mycophenolate mofetil, and cyclophosphamide have overall been disappointing. TNF-α blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis. Observational evidence strongly supports the use of anti-TNF-α agents and tocilizumab in Takayasu patients with relapsing disease. However biological agents are not curative, and relapses remain common.

  18. Effects of dam-induced landscape fragmentation on amazonian ant-plant mutualistic networks.

    Science.gov (United States)

    Emer, Carine; Venticinque, Eduardo Martins; Fonseca, Carlos Roberto

    2013-08-01

    Mutualistic networks are critical to biological diversity maintenance; however, their structures and functionality may be threatened by a swiftly changing world. In the Amazon, the increasing number of dams poses a large threat to biological diversity because they greatly alter and fragment the surrounding landscape. Tight coevolutionary interactions typical of tropical forests, such as the ant-myrmecophyte mutualism, where the myrmecophyte plants provide domatia nesting space to their symbiotic ants, may be jeopardized by the landscape changes caused by dams. We analyzed 31 ant-myrmecophyte mutualistic networks in undisturbed and disturbed sites surrounding Balbina, the largest Central Amazonian dam. We tested how ant-myrmecophyte networks differ among dam-induced islands, lake edges, and undisturbed forests in terms of species richness, composition, structure, and robustness (number of species remaining in the network after partner extinctions). We also tested how landscape configuration in terms of area, isolation, shape, and neighborhood alters the structure of the ant-myrmecophyte networks on islands. Ant-myrmecophytic networks were highly compartmentalized in undisturbed forests, and the compartments had few strongly connected mutualistic partners. In contrast, networks at lake edges and on islands were not compartmentalized and were negatively affected by island area and isolation in terms of species richness, density, and composition. Habitat loss and fragmentation led to coextinction cascades that contributed to the elimination of entire ant-plant compartments. Furthermore, many myrmecophytic plants in disturbed sites lost their mutualistic ant partners or were colonized by opportunistic, nonspecialized ants. Robustness of ant-myrmecophyte networks on islands was lower than robustness near lake edges and in undisturbed forest and was particularly susceptible to the extinction of plants. Beyond the immediate habitat loss caused by the building of large dams

  19. Biologically based neural network for mobile robot navigation

    Science.gov (United States)

    Torres Muniz, Raul E.

    1999-01-01

    The new tendency in mobile robots is to crete non-Cartesian system based on reactions to their environment. This emerging technology is known as Evolutionary Robotics, which is combined with the Biorobotic field. This new approach brings cost-effective solutions, flexibility, robustness, and dynamism into the design of mobile robots. It also provides fast reactions to the sensory inputs, and new interpretation of the environment or surroundings of the mobile robot. The Subsumption Architecture (SA) and the action selection dynamics developed by Brooks and Maes, respectively, have successfully obtained autonomous mobile robots initiating this new trend of the Evolutionary Robotics. Their design keeps the mobile robot control simple. This work present a biologically inspired modification of these schemes. The hippocampal-CA3-based neural network developed by Williams Levy is used to implement the SA, while the action selection dynamics emerge from iterations of the levels of competence implemented with the HCA3. This replacement by the HCA3 results in a closer biological model than the SA, combining the Behavior-based intelligence theory with neuroscience. The design is kept simple, and it is implemented in the Khepera Miniature Mobile Robot. The used control scheme obtains an autonomous mobile robot that can be used to execute a mail delivery system and surveillance task inside a building floor.

  20. Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data

    NARCIS (Netherlands)

    Kümmel, Anne; Panke, Sven; Heinemann, Matthias

    2006-01-01

    As one of the most recent members of the omics family, large-scale quantitative metabolomics data are currently complementing our systems biology data pool and offer the chance to integrate the metabolite level into the functional analysis of cellular networks. Network-embedded thermodynamic

  1. Parameter-free Network Sparsification and Data Reduction by Minimal Algorithmic Information Loss

    KAUST Repository

    Zenil, Hector; Kiani, Narsis A.; Tegner, Jesper

    2018-01-01

    The study of large and complex datasets, or big data, organized as networks has emerged as one of the central challenges in most areas of science and technology. Cellular and molecular networks in biology is one of the prime examples. Henceforth, a

  2. The Latin American Biological Dosimetry Network (LBDNet): Argentina, Brazil, Chile, Cuba, Mexico, Peru, Uruguay

    International Nuclear Information System (INIS)

    Guerrero C, C.; Arceo M, C.; Di Giorgio, M.; Vallerga, M.; Radl, A.; Taja, M.; Seoane, A.; De Luca, J.; Stuck O, M.; Valdivia, P.

    2010-10-01

    Biological dosimetry is a necessary support for national radiation protection programs and emergency response schemes. The Latin American Biological Dosimetry Network (LBDNet) was formally founded in 2007 for mutual assistance in case of radiation emergencies and for providing support to other Latin American countries that do not have bio dosimetry laboratories. In the frame of the IAEA Technical Cooperation Projects RLA/9/54 and RLA/9/61 the following activities have been performed: a) An international intercomparison exercise organized during 2007-2008 included six European countries and LBDNet laboratories. Relevant parameters related with dose assessment were evaluated through triage and conventional scoring criteria. A new approach for statistical data analysis was developed including assessment of inter-laboratory reproducibility and intra-laboratory repeatability. Overall, the laboratory performance was satisfactory for mutual cooperation purposes. b) In 2009, LBDNet and two European countries carried out a digital image intercomparison exercise involving dose assessment from metaphase images distributed electronically through internet. The main objectives were to evaluate scoring feasibility on metaphase images and time response. In addition a re-examination phase was considered in which the most controversial images were discussed jointly, this allowed for the development of a homogeneous scoring criteria within the network. c) A further exercise was performed during 2009 involving the shipment of biological samples for biological dosimetry assessment. The aim of this exercise was to test the timely and properly sending and receiving blood samples under national and international regulations. A total of 14 laboratories participated in this joint IAEA, PAHO and WHO. (Author)

  3. The Latin American Biological Dosimetry Network (LBDNet): Argentina, Brazil, Chile, Cuba, Mexico, Peru, Uruguay

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero C, C.; Arceo M, C. [ININ, Carretera Mexico-Toluca s/n, Ocoyoacac 52750, Estado de Mexico (Mexico); Di Giorgio, M.; Vallerga, M.; Radl, A. [Autoridad Regulatoria Nuclear, Av. del Libertador 8250, C1429 BNP CABA (Argentina); Taja, M.; Seoane, A.; De Luca, J. [Universidad Nacionald de La Plata, Av. 7 No. 1776, La Plata 1900, Buenos Aires (Argentina); Stuck O, M. [Instituto de Radioproteccion y Dosimetria, Av. Salvador Allende s/n, Recreio dos Bandeirantes, Rio de Janeiro (Brazil); Valdivia, P., E-mail: lbdnet@googlegroups.co [Comision Chilena de Energia, Amutanegui 95, Santiago Centro, Santiago (Chile)

    2010-10-15

    Biological dosimetry is a necessary support for national radiation protection programs and emergency response schemes. The Latin American Biological Dosimetry Network (LBDNet) was formally founded in 2007 for mutual assistance in case of radiation emergencies and for providing support to other Latin American countries that do not have bio dosimetry laboratories. In the frame of the IAEA Technical Cooperation Projects RLA/9/54 and RLA/9/61 the following activities have been performed: a) An international intercomparison exercise organized during 2007-2008 included six European countries and LBDNet laboratories. Relevant parameters related with dose assessment were evaluated through triage and conventional scoring criteria. A new approach for statistical data analysis was developed including assessment of inter-laboratory reproducibility and intra-laboratory repeatability. Overall, the laboratory performance was satisfactory for mutual cooperation purposes. b) In 2009, LBDNet and two European countries carried out a digital image intercomparison exercise involving dose assessment from metaphase images distributed electronically through internet. The main objectives were to evaluate scoring feasibility on metaphase images and time response. In addition a re-examination phase was considered in which the most controversial images were discussed jointly, this allowed for the development of a homogeneous scoring criteria within the network. c) A further exercise was performed during 2009 involving the shipment of biological samples for biological dosimetry assessment. The aim of this exercise was to test the timely and properly sending and receiving blood samples under national and international regulations. A total of 14 laboratories participated in this joint IAEA, PAHO and WHO. (Author)

  4. Non-parametric co-clustering of large scale sparse bipartite networks on the GPU

    DEFF Research Database (Denmark)

    Hansen, Toke Jansen; Mørup, Morten; Hansen, Lars Kai

    2011-01-01

    of row and column clusters from a hypothesis space of an infinite number of clusters. To reach large scale applications of co-clustering we exploit that parameter inference for co-clustering is well suited for parallel computing. We develop a generic GPU framework for efficient inference on large scale...... sparse bipartite networks and achieve a speedup of two orders of magnitude compared to estimation based on conventional CPUs. In terms of scalability we find for networks with more than 100 million links that reliable inference can be achieved in less than an hour on a single GPU. To efficiently manage...

  5. Measuring large-scale social networks with high resolution.

    Directory of Open Access Journals (Sweden)

    Arkadiusz Stopczynski

    Full Text Available This paper describes the deployment of a large-scale study designed to measure human interactions across a variety of communication channels, with high temporal resolution and spanning multiple years-the Copenhagen Networks Study. Specifically, we collect data on face-to-face interactions, telecommunication, social networks, location, and background information (personality, demographics, health, politics for a densely connected population of 1000 individuals, using state-of-the-art smartphones as social sensors. Here we provide an overview of the related work and describe the motivation and research agenda driving the study. Additionally, the paper details the data-types measured, and the technical infrastructure in terms of both backend and phone software, as well as an outline of the deployment procedures. We document the participant privacy procedures and their underlying principles. The paper is concluded with early results from data analysis, illustrating the importance of multi-channel high-resolution approach to data collection.

  6. Quantitative utilization of prior biological knowledge in the Bayesian network modeling of gene expression data

    Directory of Open Access Journals (Sweden)

    Gao Shouguo

    2011-08-01

    Full Text Available Abstract Background Bayesian Network (BN is a powerful approach to reconstructing genetic regulatory networks from gene expression data. However, expression data by itself suffers from high noise and lack of power. Incorporating prior biological knowledge can improve the performance. As each type of prior knowledge on its own may be incomplete or limited by quality issues, integrating multiple sources of prior knowledge to utilize their consensus is desirable. Results We introduce a new method to incorporate the quantitative information from multiple sources of prior knowledge. It first uses the Naïve Bayesian classifier to assess the likelihood of functional linkage between gene pairs based on prior knowledge. In this study we included cocitation in PubMed and schematic similarity in Gene Ontology annotation. A candidate network edge reservoir is then created in which the copy number of each edge is proportional to the estimated likelihood of linkage between the two corresponding genes. In network simulation the Markov Chain Monte Carlo sampling algorithm is adopted, and samples from this reservoir at each iteration to generate new candidate networks. We evaluated the new algorithm using both simulated and real gene expression data including that from a yeast cell cycle and a mouse pancreas development/growth study. Incorporating prior knowledge led to a ~2 fold increase in the number of known transcription regulations recovered, without significant change in false positive rate. In contrast, without the prior knowledge BN modeling is not always better than a random selection, demonstrating the necessity in network modeling to supplement the gene expression data with additional information. Conclusion our new development provides a statistical means to utilize the quantitative information in prior biological knowledge in the BN modeling of gene expression data, which significantly improves the performance.

  7. Distributed and Cooperative Link Scheduling for Large-Scale Multihop Wireless Networks

    Directory of Open Access Journals (Sweden)

    Swami Ananthram

    2007-01-01

    Full Text Available A distributed and cooperative link-scheduling (DCLS algorithm is introduced for large-scale multihop wireless networks. With this algorithm, each and every active link in the network cooperatively calibrates its environment and converges to a desired link schedule for data transmissions within a time frame of multiple slots. This schedule is such that the entire network is partitioned into a set of interleaved subnetworks, where each subnetwork consists of concurrent cochannel links that are properly separated from each other. The desired spacing in each subnetwork can be controlled by a tuning parameter and the number of time slots specified for each frame. Following the DCLS algorithm, a distributed and cooperative power control (DCPC algorithm can be applied to each subnetwork to ensure a desired data rate for each link with minimum network transmission power. As shown consistently by simulations, the DCLS algorithm along with a DCPC algorithm yields significant power savings. The power savings also imply an increased feasible region of averaged link data rates for the entire network.

  8. Distributed and Cooperative Link Scheduling for Large-Scale Multihop Wireless Networks

    Directory of Open Access Journals (Sweden)

    Ananthram Swami

    2007-12-01

    Full Text Available A distributed and cooperative link-scheduling (DCLS algorithm is introduced for large-scale multihop wireless networks. With this algorithm, each and every active link in the network cooperatively calibrates its environment and converges to a desired link schedule for data transmissions within a time frame of multiple slots. This schedule is such that the entire network is partitioned into a set of interleaved subnetworks, where each subnetwork consists of concurrent cochannel links that are properly separated from each other. The desired spacing in each subnetwork can be controlled by a tuning parameter and the number of time slots specified for each frame. Following the DCLS algorithm, a distributed and cooperative power control (DCPC algorithm can be applied to each subnetwork to ensure a desired data rate for each link with minimum network transmission power. As shown consistently by simulations, the DCLS algorithm along with a DCPC algorithm yields significant power savings. The power savings also imply an increased feasible region of averaged link data rates for the entire network.

  9. ShakeNet: a portable wireless sensor network for instrumenting large civil structures

    Science.gov (United States)

    Kohler, Monica D.; Hao, Shuai; Mishra, Nilesh; Govindan, Ramesh; Nigbor, Robert

    2015-08-03

    We report our findings from a U.S. Geological Survey (USGS) National Earthquake Hazards Reduction Program-funded project to develop and test a wireless, portable, strong-motion network of up to 40 triaxial accelerometers for structural health monitoring. The overall goal of the project was to record ambient vibrations for several days from USGS-instrumented structures. Structural health monitoring has important applications in fields like civil engineering and the study of earthquakes. The emergence of wireless sensor networks provides a promising means to such applications. However, while most wireless sensor networks are still in the experimentation stage, very few take into consideration the realistic earthquake engineering application requirements. To collect comprehensive data for structural health monitoring for civil engineers, high-resolution vibration sensors and sufficient sampling rates should be adopted, which makes it challenging for current wireless sensor network technology in the following ways: processing capabilities, storage limit, and communication bandwidth. The wireless sensor network has to meet expectations set by wired sensor devices prevalent in the structural health monitoring community. For this project, we built and tested an application-realistic, commercially based, portable, wireless sensor network called ShakeNet for instrumentation of large civil structures, especially for buildings, bridges, or dams after earthquakes. Two to three people can deploy ShakeNet sensors within hours after an earthquake to measure the structural response of the building or bridge during aftershocks. ShakeNet involved the development of a new sensing platform (ShakeBox) running a software suite for networking, data collection, and monitoring. Deployments reported here on a tall building and a large dam were real-world tests of ShakeNet operation, and helped to refine both hardware and software. 

  10. Structuring heterogeneous biological information using fuzzy clustering of k-partite graphs

    Directory of Open Access Journals (Sweden)

    Theis Fabian J

    2010-10-01

    Full Text Available Abstract Background Extensive and automated data integration in bioinformatics facilitates the construction of large, complex biological networks. However, the challenge lies in the interpretation of these networks. While most research focuses on the unipartite or bipartite case, we address the more general but common situation of k-partite graphs. These graphs contain k different node types and links are only allowed between nodes of different types. In order to reveal their structural organization and describe the contained information in a more coarse-grained fashion, we ask how to detect clusters within each node type. Results Since entities in biological networks regularly have more than one function and hence participate in more than one cluster, we developed a k-partite graph partitioning algorithm that allows for overlapping (fuzzy clusters. It determines for each node a degree of membership to each cluster. Moreover, the algorithm estimates a weighted k-partite graph that connects the extracted clusters. Our method is fast and efficient, mimicking the multiplicative update rules commonly employed in algorithms for non-negative matrix factorization. It facilitates the decomposition of networks on a chosen scale and therefore allows for analysis and interpretation of structures on various resolution levels. Applying our algorithm to a tripartite disease-gene-protein complex network, we were able to structure this graph on a large scale into clusters that are functionally correlated and biologically meaningful. Locally, smaller clusters enabled reclassification or annotation of the clusters' elements. We exemplified this for the transcription factor MECP2. Conclusions In order to cope with the overwhelming amount of information available from biomedical literature, we need to tackle the challenge of finding structures in large networks with nodes of multiple types. To this end, we presented a novel fuzzy k-partite graph partitioning

  11. Large-scale changes in network interactions as a physiological signature of spatial neglect.

    Science.gov (United States)

    Baldassarre, Antonello; Ramsey, Lenny; Hacker, Carl L; Callejas, Alicia; Astafiev, Serguei V; Metcalf, Nicholas V; Zinn, Kristi; Rengachary, Jennifer; Snyder, Abraham Z; Carter, Alex R; Shulman, Gordon L; Corbetta, Maurizio

    2014-12-01

    The relationship between spontaneous brain activity and behaviour following focal injury is not well understood. Here, we report a large-scale study of resting state functional connectivity MRI and spatial neglect following stroke in a large (n=84) heterogeneous sample of first-ever stroke patients (within 1-2 weeks). Spatial neglect, which is typically more severe after right than left hemisphere injury, includes deficits of spatial attention and motor actions contralateral to the lesion, and low general attention due to impaired vigilance/arousal. Patients underwent structural and resting state functional MRI scans, and spatial neglect was measured using the Posner spatial cueing task, and Mesulam and Behavioural Inattention Test cancellation tests. A principal component analysis of the behavioural tests revealed a main factor accounting for 34% of variance that captured three correlated behavioural deficits: visual neglect of the contralesional visual field, visuomotor neglect of the contralesional field, and low overall performance. In an independent sample (21 healthy subjects), we defined 10 resting state networks consisting of 169 brain regions: visual-fovea and visual-periphery, sensory-motor, auditory, dorsal attention, ventral attention, language, fronto-parietal control, cingulo-opercular control, and default mode. We correlated the neglect factor score with the strength of resting state functional connectivity within and across the 10 resting state networks. All damaged brain voxels were removed from the functional connectivity:behaviour correlational analysis. We found that the correlated behavioural deficits summarized by the factor score were associated with correlated multi-network patterns of abnormal functional connectivity involving large swaths of cortex. Specifically, dorsal attention and sensory-motor networks showed: (i) reduced interhemispheric functional connectivity; (ii) reduced anti-correlation with fronto-parietal and default mode

  12. Local, distributed topology control for large-scale wireless ad-hoc networks

    NARCIS (Netherlands)

    Nieberg, T.; Hurink, Johann L.

    In this document, topology control of a large-scale, wireless network by a distributed algorithm that uses only locally available information is presented. Topology control algorithms adjust the transmission power of wireless nodes to create a desired topology. The algorithm, named local power

  13. Preserving biological diversity in the face of large-scale demands for biofuels

    International Nuclear Information System (INIS)

    Cook, J.J.; Beyea, J.; Keeler, K.H.

    1991-01-01

    Large-scale production and harvesting of biomass to replace fossil fuels could reduce biological diversity by eliminating habitat for native species. Forests would be managed and harvested more intensively, and virtually all arable land unsuitable for high-value agriculture or silviculture might be used to grow crops dedicated to energy. Given the prospects for a potentially large increase in biofuel production, it is time now to develop strategies for mitigating the loss of biodiversity that might ensue. Planning at micro to macro scales will be crucial to minimize the ecological impacts of producing biofuels. In particular, cropping and harvesting systems will need to provide the biological, spatial, and temporal diversity characteristics of natural ecosystems and successional sequences, if we are to have this technology support the environmental health of the world rather than compromise it. Incorporation of these ecological values will be necessary to forestall costly environmental restoration, even at the cost of submaximal biomass productivity. It is therefore doubtful that all managers will take the longer view. Since the costs of biodiversity loss are largely external to economic markets, society cannot rely on the market to protect biodiversity, and some sort of intervention will be necessary. 116 refs., 1 tab

  14. Robust Learning of High-dimensional Biological Networks with Bayesian Networks

    Science.gov (United States)

    Nägele, Andreas; Dejori, Mathäus; Stetter, Martin

    Structure learning of Bayesian networks applied to gene expression data has become a potentially useful method to estimate interactions between genes. However, the NP-hardness of Bayesian network structure learning renders the reconstruction of the full genetic network with thousands of genes unfeasible. Consequently, the maximal network size is usually restricted dramatically to a small set of genes (corresponding with variables in the Bayesian network). Although this feature reduction step makes structure learning computationally tractable, on the downside, the learned structure might be adversely affected due to the introduction of missing genes. Additionally, gene expression data are usually very sparse with respect to the number of samples, i.e., the number of genes is much greater than the number of different observations. Given these problems, learning robust network features from microarray data is a challenging task. This chapter presents several approaches tackling the robustness issue in order to obtain a more reliable estimation of learned network features.

  15. Congenital blindness is associated with large-scale reorganization of anatomical networks.

    Science.gov (United States)

    Hasson, Uri; Andric, Michael; Atilgan, Hicret; Collignon, Olivier

    2016-03-01

    Blindness is a unique model for understanding the role of experience in the development of the brain's functional and anatomical architecture. Documenting changes in the structure of anatomical networks for this population would substantiate the notion that the brain's core network-level organization may undergo neuroplasticity as a result of life-long experience. To examine this issue, we compared whole-brain networks of regional cortical-thickness covariance in early blind and matched sighted individuals. This covariance is thought to reflect signatures of integration between systems involved in similar perceptual/cognitive functions. Using graph-theoretic metrics, we identified a unique mode of anatomical reorganization in the blind that differed from that found for sighted. This was seen in that network partition structures derived from subgroups of blind were more similar to each other than they were to partitions derived from sighted. Notably, after deriving network partitions, we found that language and visual regions tended to reside within separate modules in sighted but showed a pattern of merging into shared modules in the blind. Our study demonstrates that early visual deprivation triggers a systematic large-scale reorganization of whole-brain cortical-thickness networks, suggesting changes in how occipital regions interface with other functional networks in the congenitally blind. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Role of Delays in Shaping Spatiotemporal Dynamics of Neuronal Activity in Large Networks

    International Nuclear Information System (INIS)

    Roxin, Alex; Brunel, Nicolas; Hansel, David

    2005-01-01

    We study the effect of delays on the dynamics of large networks of neurons. We show that delays give rise to a wealth of bifurcations and to a rich phase diagram, which includes oscillatory bumps, traveling waves, lurching waves, standing waves arising via a period-doubling bifurcation, aperiodic regimes, and regimes of multistability. We study the existence and the stability of the various dynamical patterns analytically and numerically in a simplified rate model as a function of the interaction parameters. The results derived in that framework allow us to understand the origin of the diversity of dynamical states observed in large networks of spiking neurons

  17. Gene coexpression network analysis as a source of functional annotation for rice genes.

    Directory of Open Access Journals (Sweden)

    Kevin L Childs

    Full Text Available With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional

  18. Large scale silver nanowires network fabricated by MeV hydrogen (H+) ion beam irradiation

    International Nuclear Information System (INIS)

    S, Honey; S, Naseem; A, Ishaq; M, Maaza; M T, Bhatti; D, Wan

    2016-01-01

    A random two-dimensional large scale nano-network of silver nanowires (Ag-NWs) is fabricated by MeV hydrogen (H + ) ion beam irradiation. Ag-NWs are irradiated under H +  ion beam at different ion fluences at room temperature. The Ag-NW network is fabricated by H + ion beam-induced welding of Ag-NWs at intersecting positions. H +  ion beam induced welding is confirmed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Moreover, the structure of Ag NWs remains stable under H +  ion beam, and networks are optically transparent. Morphology also remains stable under H +  ion beam irradiation. No slicings or cuttings of Ag-NWs are observed under MeV H +  ion beam irradiation. The results exhibit that the formation of Ag-NW network proceeds through three steps: ion beam induced thermal spikes lead to the local heating of Ag-NWs, the formation of simple junctions on small scale, and the formation of a large scale network. This observation is useful for using Ag-NWs based devices in upper space where protons are abandoned in an energy range from MeV to GeV. This high-quality Ag-NW network can also be used as a transparent electrode for optoelectronics devices. (paper)

  19. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa Jane; Freude, Kristine

    2016-01-01

    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...

  20. Automated, feature-based image alignment for high-resolution imaging mass spectrometry of large biological samples

    NARCIS (Netherlands)

    Broersen, A.; Liere, van R.; Altelaar, A.F.M.; Heeren, R.M.A.; McDonnell, L.A.

    2008-01-01

    High-resolution imaging mass spectrometry of large biological samples is the goal of several research groups. In mosaic imaging, the most common method, the large sample is divided into a mosaic of small areas that are then analyzed with high resolution. Here we present an automated alignment

  1. 78 FR 70076 - Large Scale Networking (LSN)-Middleware and Grid Interagency Coordination (MAGIC) Team

    Science.gov (United States)

    2013-11-22

    ... projects. The MAGIC Team reports to the Large Scale Networking (LSN) Coordinating Group (CG). Public... Coordination (MAGIC) Team AGENCY: The Networking and Information Technology Research and Development (NITRD... MAGIC Team meetings are held on the first Wednesday of each month, 2:00-4:00 p.m., at the National...

  2. Major technological innovations introduced in the large antennas of the Deep Space Network

    Science.gov (United States)

    Imbriale, W. A.

    2002-01-01

    The NASA Deep Space Network (DSN) is the largest and most sensitive scientific, telecommunications and radio navigation network in the world. Its principal responsibilities are to provide communications, tracking, and science services to most of the world's spacecraft that travel beyond low Earth orbit. The network consists of three Deep Space Communications Complexes. Each of the three complexes consists of multiple large antennas equipped with ultra sensitive receiving systems. A centralized Signal Processing Center (SPC) remotely controls the antennas, generates and transmits spacecraft commands, and receives and processes the spacecraft telemetry.

  3. Suspended sediment transport trough a large fluvial-tidal channel network

    Science.gov (United States)

    Wright, Scott A.; Morgan-King, Tara L.

    2015-01-01

    The confluence of the Sacramento and San Joaquin Rivers, CA, forms a large network of interconnected channels, referred to as the Sacramento-San Joaquin Delta (the Delta). The Delta comprises the transition zone from the fluvial influences of the upstream rivers and tidal influences of San Francisco Bay downstream. Formerly an extensive tidal marsh, the hydrodynamics and geomorphology of Delta have been substantially modified by humans to support agriculture, navigation, and water supply. These modifications, including construction of new channels, diking and draining of tidal wetlands, dredging of navigation channels, and the operation of large pumping facilities for distribution of freshwater from the Delta to other parts of the state, have had a dramatic impact on the physical and ecological processes within the Delta. To better understand the current physical processes, and their linkages to ecological processes, the USGS maintains an extensive network of flow, sediment, and water quality gages in the Delta. Flow gaging is accomplished through use of the index-velocity method, and sediment monitoring uses turbidity as a surrogate for suspended-sediment concentration. Herein, we present analyses of the transport and dispersal of suspended sediment through the complex network of channels in the Delta. The primary source of sediment to the Delta is the Sacramento River, which delivers pulses of sediment primarily during winter and spring runoff events. Upon reaching the Delta, the sediment pulses move through the fluvial-tidal transition while also encountering numerous channel junctions as the Sacramento River branches into several distributary channels. The monitoring network allows us to track these pulses through the network and document the dominant transport pathways for suspended sediment. Further, the flow gaging allows for an assessment of the relative effects of advection (the fluvial signal) and dispersion (from the tides) on the sediment pulses as they

  4. Coordinated SLNR based Precoding in Large-Scale Heterogeneous Networks

    KAUST Repository

    Boukhedimi, Ikram

    2017-03-06

    This work focuses on the downlink of large-scale two-tier heterogeneous networks composed of a macro-cell overlaid by micro-cell networks. Our interest is on the design of coordinated beamforming techniques that allow to mitigate the inter-cell interference. Particularly, we consider the case in which the coordinating base stations (BSs) have imperfect knowledge of the channel state information. Under this setting, we propose a regularized SLNR based precoding design in which the regularization factor is used to allow better resilience with respect to the channel estimation errors. Based on tools from random matrix theory, we provide an analytical analysis of the SINR and SLNR performances. These results are then exploited to propose a proper setting of the regularization factor. Simulation results are finally provided in order to validate our findings and to confirm the performance of the proposed precoding scheme.

  5. Coordinated SLNR based Precoding in Large-Scale Heterogeneous Networks

    KAUST Repository

    Boukhedimi, Ikram; Kammoun, Abla; Alouini, Mohamed-Slim

    2017-01-01

    This work focuses on the downlink of large-scale two-tier heterogeneous networks composed of a macro-cell overlaid by micro-cell networks. Our interest is on the design of coordinated beamforming techniques that allow to mitigate the inter-cell interference. Particularly, we consider the case in which the coordinating base stations (BSs) have imperfect knowledge of the channel state information. Under this setting, we propose a regularized SLNR based precoding design in which the regularization factor is used to allow better resilience with respect to the channel estimation errors. Based on tools from random matrix theory, we provide an analytical analysis of the SINR and SLNR performances. These results are then exploited to propose a proper setting of the regularization factor. Simulation results are finally provided in order to validate our findings and to confirm the performance of the proposed precoding scheme.

  6. Patterns of interactions of a large fish-parasite network in a tropical floodplain.

    Science.gov (United States)

    Lima, Dilermando P; Giacomini, Henrique C; Takemoto, Ricardo M; Agostinho, Angelo A; Bini, Luis M

    2012-07-01

    1. Describing and explaining the structure of species interaction networks is of paramount importance for community ecology. Yet much has to be learned about the mechanisms responsible for major patterns, such as nestedness and modularity in different kinds of systems, of which large and diverse networks are a still underrepresented and scarcely studied fraction. 2. We assembled information on fishes and their parasites living in a large floodplain of key ecological importance for freshwater ecosystems in the Paraná River basin in South America. The resulting fish-parasite network containing 72 and 324 species of fishes and parasites, respectively, was analysed to investigate the patterns of nestedness and modularity as related to fish and parasite features. 3. Nestedness was found in the entire network and among endoparasites, multiple-host life cycle parasites and native hosts, but not in networks of ectoparasites, single-host life cycle parasites and non-native fishes. All networks were significantly modular. Taxonomy was the major host's attribute influencing both nestedness and modularity: more closely related host species tended to be associated with more nested parasite compositions and had greater chance of belonging to the same network module. Nevertheless, host abundance had a positive relationship with nestedness when only native host species pairs of the same network module were considered for analysis. 4. These results highlight the importance of evolutionary history of hosts in linking patterns of nestedness and formation of modules in the network. They also show that functional attributes of parasites (i.e. parasitism mode and life cycle) and origin of host populations (i.e. natives versus non-natives) are crucial to define the relative contribution of these two network properties and their dependence on other ecological factors (e.g. host abundance), with potential implications for community dynamics and stability. © 2012 The Authors

  7. Endogenous Molecular-Cellular Network Cancer Theory: A Systems Biology Approach.

    Science.gov (United States)

    Wang, Gaowei; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

    2018-01-01

    In light of ever apparent limitation of the current dominant cancer mutation theory, a quantitative hypothesis for cancer genesis and progression, endogenous molecular-cellular network hypothesis has been proposed from the systems biology perspective, now for more than 10 years. It was intended to include both the genetic and epigenetic causes to understand cancer. Its development enters the stage of meaningful interaction with experimental and clinical data and the limitation of the traditional cancer mutation theory becomes more evident. Under this endogenous network hypothesis, we established a core working network of hepatocellular carcinoma (HCC) according to the hypothesis and quantified the working network by a nonlinear dynamical system. We showed that the two stable states of the working network reproduce the main known features of normal liver and HCC at both the modular and molecular levels. Using endogenous network hypothesis and validated working network, we explored genetic mutation pattern in cancer and potential strategies to cure or relieve HCC from a totally new perspective. Patterns of genetic mutations have been traditionally analyzed by posteriori statistical association approaches in light of traditional cancer mutation theory. One may wonder the possibility of a priori determination of any mutation regularity. Here, we found that based on the endogenous network theory the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. Normal hepatocyte and cancerous hepatocyte stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable

  8. Biological intrusion barriers for large-volume waste-disposal sites

    International Nuclear Information System (INIS)

    Hakonson, T.E.; Cline, J.F.; Rickard, W.H.

    1982-01-01

    intrusion of plants and animals into shallow land burial sites with subsequent mobilization of toxic and radiotoxic materials has occured. Based on recent pathway modeling studies, such intrusions can contribute to the dose received by man. This paper describes past work on developing biological intrusion barrier systems for application to large volume waste site stabilization. State-of-the-art concepts employing rock and chemical barriers are discussed relative to long term serviceability and cost of application. The interaction of bio-intrusion barrier systems with other processes affecting trench cover stability are discussed to ensure that trench cover designs minimize the potential dose to man. 3 figures, 6 tables

  9. How Did the Information Flow in the #AlphaGo Hashtag Network? A Social Network Analysis of the Large-Scale Information Network on Twitter.

    Science.gov (United States)

    Kim, Jinyoung

    2017-12-01

    As it becomes common for Internet users to use hashtags when posting and searching information on social media, it is important to understand who builds a hashtag network and how information is circulated within the network. This article focused on unlocking the potential of the #AlphaGo hashtag network by addressing the following questions. First, the current study examined whether traditional opinion leadership (i.e., the influentials hypothesis) or grassroot participation by the public (i.e., the interpersonal hypothesis) drove dissemination of information in the hashtag network. Second, several unique patterns of information distribution by key users were identified. Finally, the association between attributes of key users who exerted great influence on information distribution (i.e., the number of followers and follows) and their central status in the network was tested. To answer the proffered research questions, a social network analysis was conducted using a large-scale hashtag network data set from Twitter (n = 21,870). The results showed that the leading actors in the network were actively receiving information from their followers rather than serving as intermediaries between the original information sources and the public. Moreover, the leading actors played several roles (i.e., conversation starters, influencers, and active engagers) in the network. Furthermore, the number of their follows and followers were significantly associated with their central status in the hashtag network. Based on the results, the current research explained how the information was exchanged in the hashtag network by proposing the reciprocal model of information flow.

  10. 77 FR 58416 - Large Scale Networking (LSN); Middleware and Grid Interagency Coordination (MAGIC) Team

    Science.gov (United States)

    2012-09-20

    ..., Grid, and cloud projects. The MAGIC Team reports to the Large Scale Networking (LSN) Coordinating Group... Coordination (MAGIC) Team AGENCY: The Networking and Information Technology Research and Development (NITRD.... Dates/Location: The MAGIC Team meetings are held on the first Wednesday of each month, 2:00-4:00pm, at...

  11. Biological engineering applications of feedforward neural networks designed and parameterized by genetic algorithms.

    Science.gov (United States)

    Ferentinos, Konstantinos P

    2005-09-01

    Two neural network (NN) applications in the field of biological engineering are developed, designed and parameterized by an evolutionary method based on the evolutionary process of genetic algorithms. The developed systems are a fault detection NN model and a predictive modeling NN system. An indirect or 'weak specification' representation was used for the encoding of NN topologies and training parameters into genes of the genetic algorithm (GA). Some a priori knowledge of the demands in network topology for specific application cases is required by this approach, so that the infinite search space of the problem is limited to some reasonable degree. Both one-hidden-layer and two-hidden-layer network architectures were explored by the GA. Except for the network architecture, each gene of the GA also encoded the type of activation functions in both hidden and output nodes of the NN and the type of minimization algorithm that was used by the backpropagation algorithm for the training of the NN. Both models achieved satisfactory performance, while the GA system proved to be a powerful tool that can successfully replace the problematic trial-and-error approach that is usually used for these tasks.

  12. Towards a Versatile Problem Diagnosis Infrastructure for LargeWireless Sensor Networks

    NARCIS (Netherlands)

    Iwanicki, Konrad; Steen, van Maarten

    2007-01-01

    In this position paper, we address the issue of durable maintenance of a wireless sensor network, which will be crucial if the vision of large, long-lived sensornets is to become reality. Durable maintenance requires tools for diagnosing and fixing occurring problems, which can range from

  13. Neural network models for biological waste-gas treatment systems.

    Science.gov (United States)

    Rene, Eldon R; Estefanía López, M; Veiga, María C; Kennes, Christian

    2011-12-15

    This paper outlines the procedure for developing artificial neural network (ANN) based models for three bioreactor configurations used for waste-gas treatment. The three bioreactor configurations chosen for this modelling work were: biofilter (BF), continuous stirred tank bioreactor (CSTB) and monolith bioreactor (MB). Using styrene as the model pollutant, this paper also serves as a general database of information pertaining to the bioreactor operation and important factors affecting gas-phase styrene removal in these biological systems. Biological waste-gas treatment systems are considered to be both advantageous and economically effective in treating a stream of polluted air containing low to moderate concentrations of the target contaminant, over a rather wide range of gas-flow rates. The bioreactors were inoculated with the fungus Sporothrix variecibatus, and their performances were evaluated at different empty bed residence times (EBRT), and at different inlet styrene concentrations (C(i)). The experimental data from these bioreactors were modelled to predict the bioreactors performance in terms of their removal efficiency (RE, %), by adequate training and testing of a three-layered back propagation neural network (input layer-hidden layer-output layer). Two models (BIOF1 and BIOF2) were developed for the BF with different combinations of easily measurable BF parameters as the inputs, that is concentration (gm(-3)), unit flow (h(-1)) and pressure drop (cm of H(2)O). The model developed for the CSTB used two inputs (concentration and unit flow), while the model for the MB had three inputs (concentration, G/L (gas/liquid) ratio, and pressure drop). Sensitivity analysis in the form of absolute average sensitivity (AAS) was performed for all the developed ANN models to ascertain the importance of the different input parameters, and to assess their direct effect on the bioreactors performance. The performance of the models was estimated by the regression

  14. A large scale analysis of information-theoretic network complexity measures using chemical structures.

    Directory of Open Access Journals (Sweden)

    Matthias Dehmer

    Full Text Available This paper aims to investigate information-theoretic network complexity measures which have already been intensely used in mathematical- and medicinal chemistry including drug design. Numerous such measures have been developed so far but many of them lack a meaningful interpretation, e.g., we want to examine which kind of structural information they detect. Therefore, our main contribution is to shed light on the relatedness between some selected information measures for graphs by performing a large scale analysis using chemical networks. Starting from several sets containing real and synthetic chemical structures represented by graphs, we study the relatedness between a classical (partition-based complexity measure called the topological information content of a graph and some others inferred by a different paradigm leading to partition-independent measures. Moreover, we evaluate the uniqueness of network complexity measures numerically. Generally, a high uniqueness is an important and desirable property when designing novel topological descriptors having the potential to be applied to large chemical databases.

  15. Evolutionary optimization with data collocation for reverse engineering of biological networks.

    Science.gov (United States)

    Tsai, Kuan-Yao; Wang, Feng-Sheng

    2005-04-01

    Modern experimental biology is moving away from analyses of single elements to whole-organism measurements. Such measured time-course data contain a wealth of information about the structure and dynamic of the pathway or network. The dynamic modeling of the whole systems is formulated as a reverse problem that requires a well-suited mathematical model and a very efficient computational method to identify the model structure and parameters. Numerical integration for differential equations and finding global parameter values are still two major challenges in this field of the parameter estimation of nonlinear dynamic biological systems. We compare three techniques of parameter estimation for nonlinear dynamic biological systems. In the proposed scheme, the modified collocation method is applied to convert the differential equations to the system of algebraic equations. The observed time-course data are then substituted into the algebraic system equations to decouple system interactions in order to obtain the approximate model profiles. Hybrid differential evolution (HDE) with population size of five is able to find a global solution. The method is not only suited for parameter estimation but also can be applied for structure identification. The solution obtained by HDE is then used as the starting point for a local search method to yield the refined estimates.

  16. Large-scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function.

    Science.gov (United States)

    Lerman, Caryn; Gu, Hong; Loughead, James; Ruparel, Kosha; Yang, Yihong; Stein, Elliot A

    2014-05-01

    Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders. To test the hypothesis that the strength of coupling among 3 large-scale brain networks--salience, executive control, and default mode--will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks. A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses. Twenty-four hours of abstinence vs smoking satiety. Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary). The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P = .002; right RAI, P = .04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = -0.59; P = .007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = -0.66, P = .003; posterior cingulate cortex, r = -0.65, P = .001). Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may be critical in cognitive/affective alterations that underlie nicotine dependence.

  17. MapReduce Based Parallel Neural Networks in Enabling Large Scale Machine Learning.

    Science.gov (United States)

    Liu, Yang; Yang, Jie; Huang, Yuan; Xu, Lixiong; Li, Siguang; Qi, Man

    2015-01-01

    Artificial neural networks (ANNs) have been widely used in pattern recognition and classification applications. However, ANNs are notably slow in computation especially when the size of data is large. Nowadays, big data has received a momentum from both industry and academia. To fulfill the potentials of ANNs for big data applications, the computation process must be speeded up. For this purpose, this paper parallelizes neural networks based on MapReduce, which has become a major computing model to facilitate data intensive applications. Three data intensive scenarios are considered in the parallelization process in terms of the volume of classification data, the size of the training data, and the number of neurons in the neural network. The performance of the parallelized neural networks is evaluated in an experimental MapReduce computer cluster from the aspects of accuracy in classification and efficiency in computation.

  18. FiBi - A French network of facilities for irradiation in biology: The organisation of the network and the research opportunities associated

    International Nuclear Information System (INIS)

    Gaillard-Lecanu, E.; Coffigny, H.; Poncy, J.L.; Authier, N.; Verrey, B.; Bailly, I.; Baldacchino, G.; Bordy, J.M.; Carriere, M.; Leplat, J.J.; Pin, S.; Pommeret, S.; Thuret, J.Y.; Renault, J.P.; Cortella, I.; Duval, D.; Khodja, H.; Testard, I.

    2006-01-01

    The Life Science Division of the Atomic Energy Commission has developed a national network of available irradiation facilities for biological studies. One aim is to optimise the irradiation of biological samples, through a compendium of existing facilities allowing for the preserving and the irradiation of these samples in good conditions, and for providing an appropriate and reliable dosimetry. Given the high cost of the facilities and their specialization (nature and precision of irradiation on a cell scale, dose and dose rate), closeness is no longer the only criteria of choice for biologists. Development is leaning towards the implementation of irradiation platforms gathering irradiation tools associated with specific methods belonging to biology: cell culture, molecular biology and even animal care houses. The aim is to be able to offer biologists the most appropriate experimental tools, and to modify them according to the changing needs of radiobiology. This work is currently in progress and the database is still not exhaustive and shall be implemented as and when new documents are drawn up and new facilities are opened. (author)

  19. Enabling Controlling Complex Networks with Local Topological Information.

    Science.gov (United States)

    Li, Guoqi; Deng, Lei; Xiao, Gaoxi; Tang, Pei; Wen, Changyun; Hu, Wuhua; Pei, Jing; Shi, Luping; Stanley, H Eugene

    2018-03-15

    Complex networks characterize the nature of internal/external interactions in real-world systems including social, economic, biological, ecological, and technological networks. Two issues keep as obstacles to fulfilling control of large-scale networks: structural controllability which describes the ability to guide a dynamical system from any initial state to any desired final state in finite time, with a suitable choice of inputs; and optimal control, which is a typical control approach to minimize the cost for driving the network to a predefined state with a given number of control inputs. For large complex networks without global information of network topology, both problems remain essentially open. Here we combine graph theory and control theory for tackling the two problems in one go, using only local network topology information. For the structural controllability problem, a distributed local-game matching method is proposed, where every node plays a simple Bayesian game with local information and local interactions with adjacent nodes, ensuring a suboptimal solution at a linear complexity. Starring from any structural controllability solution, a minimizing longest control path method can efficiently reach a good solution for the optimal control in large networks. Our results provide solutions for distributed complex network control and demonstrate a way to link the structural controllability and optimal control together.

  20. Just-in-time connectivity for large spiking networks.

    Science.gov (United States)

    Lytton, William W; Omurtag, Ahmet; Neymotin, Samuel A; Hines, Michael L

    2008-11-01

    The scale of large neuronal network simulations is memory limited due to the need to store connectivity information: connectivity storage grows as the square of neuron number up to anatomically relevant limits. Using the NEURON simulator as a discrete-event simulator (no integration), we explored the consequences of avoiding the space costs of connectivity through regenerating connectivity parameters when needed: just in time after a presynaptic cell fires. We explored various strategies for automated generation of one or more of the basic static connectivity parameters: delays, postsynaptic cell identities, and weights, as well as run-time connectivity state: the event queue. Comparison of the JitCon implementation to NEURON's standard NetCon connectivity method showed substantial space savings, with associated run-time penalty. Although JitCon saved space by eliminating connectivity parameters, larger simulations were still memory limited due to growth of the synaptic event queue. We therefore designed a JitEvent algorithm that added items to the queue only when required: instead of alerting multiple postsynaptic cells, a spiking presynaptic cell posted a callback event at the shortest synaptic delay time. At the time of the callback, this same presynaptic cell directly notified the first postsynaptic cell and generated another self-callback for the next delay time. The JitEvent implementation yielded substantial additional time and space savings. We conclude that just-in-time strategies are necessary for very large network simulations but that a variety of alternative strategies should be considered whose optimality will depend on the characteristics of the simulation to be run.

  1. Information flow analysis of interactome networks.

    Directory of Open Access Journals (Sweden)

    Patrycja Vasilyev Missiuro

    2009-04-01

    Full Text Available Recent studies of cellular networks have revealed modular organizations of genes and proteins. For example, in interactome networks, a module refers to a group of interacting proteins that form molecular complexes and/or biochemical pathways and together mediate a biological process. However, it is still poorly understood how biological information is transmitted between different modules. We have developed information flow analysis, a new computational approach that identifies proteins central to the transmission of biological information throughout the network. In the information flow analysis, we represent an interactome network as an electrical circuit, where interactions are modeled as resistors and proteins as interconnecting junctions. Construing the propagation of biological signals as flow of electrical current, our method calculates an information flow score for every protein. Unlike previous metrics of network centrality such as degree or betweenness that only consider topological features, our approach incorporates confidence scores of protein-protein interactions and automatically considers all possible paths in a network when evaluating the importance of each protein. We apply our method to the interactome networks of Saccharomyces cerevisiae and Caenorhabditis elegans. We find that the likelihood of observing lethality and pleiotropy when a protein is eliminated is positively correlated with the protein's information flow score. Even among proteins of low degree or low betweenness, high information scores serve as a strong predictor of loss-of-function lethality or pleiotropy. The correlation between information flow scores and phenotypes supports our hypothesis that the proteins of high information flow reside in central positions in interactome networks. We also show that the ranks of information flow scores are more consistent than that of betweenness when a large amount of noisy data is added to an interactome. Finally, we

  2. CUFID-query: accurate network querying through random walk based network flow estimation.

    Science.gov (United States)

    Jeong, Hyundoo; Qian, Xiaoning; Yoon, Byung-Jun

    2017-12-28

    Functional modules in biological networks consist of numerous biomolecules and their complicated interactions. Recent studies have shown that biomolecules in a functional module tend to have similar interaction patterns and that such modules are often conserved across biological networks of different species. As a result, such conserved functional modules can be identified through comparative analysis of biological networks. In this work, we propose a novel network querying algorithm based on the CUFID (Comparative network analysis Using the steady-state network Flow to IDentify orthologous proteins) framework combined with an efficient seed-and-extension approach. The proposed algorithm, CUFID-query, can accurately detect conserved functional modules as small subnetworks in the target network that are expected to perform similar functions to the given query functional module. The CUFID framework was recently developed for probabilistic pairwise global comparison of biological networks, and it has been applied to pairwise global network alignment, where the framework was shown to yield accurate network alignment results. In the proposed CUFID-query algorithm, we adopt the CUFID framework and extend it for local network alignment, specifically to solve network querying problems. First, in the seed selection phase, the proposed method utilizes the CUFID framework to compare the query and the target networks and to predict the probabilistic node-to-node correspondence between the networks. Next, the algorithm selects and greedily extends the seed in the target network by iteratively adding nodes that have frequent interactions with other nodes in the seed network, in a way that the conductance of the extended network is maximally reduced. Finally, CUFID-query removes irrelevant nodes from the querying results based on the personalized PageRank vector for the induced network that includes the fully extended network and its neighboring nodes. Through extensive

  3. Complex and unexpected dynamics in simple genetic regulatory networks

    Science.gov (United States)

    Borg, Yanika; Ullner, Ekkehard; Alagha, Afnan; Alsaedi, Ahmed; Nesbeth, Darren; Zaikin, Alexey

    2014-03-01

    One aim of synthetic biology is to construct increasingly complex genetic networks from interconnected simpler ones to address challenges in medicine and biotechnology. However, as systems increase in size and complexity, emergent properties lead to unexpected and complex dynamics due to nonlinear and nonequilibrium properties from component interactions. We focus on four different studies of biological systems which exhibit complex and unexpected dynamics. Using simple synthetic genetic networks, small and large populations of phase-coupled quorum sensing repressilators, Goodwin oscillators, and bistable switches, we review how coupled and stochastic components can result in clustering, chaos, noise-induced coherence and speed-dependent decision making. A system of repressilators exhibits oscillations, limit cycles, steady states or chaos depending on the nature and strength of the coupling mechanism. In large repressilator networks, rich dynamics can also be exhibited, such as clustering and chaos. In populations of Goodwin oscillators, noise can induce coherent oscillations. In bistable systems, the speed with which incoming external signals reach steady state can bias the network towards particular attractors. These studies showcase the range of dynamical behavior that simple synthetic genetic networks can exhibit. In addition, they demonstrate the ability of mathematical modeling to analyze nonlinearity and inhomogeneity within these systems.