Sample records for biological network analysis

  1. Introduction to Network Analysis in Systems Biology


    Ma’ayan, Avi


    This Teaching Resource provides lecture notes, slides, and a problem set for a set of three lectures from a course entitled “Systems Biology: Biomedical Modeling.” The materials are from three separate lectures introducing applications of graph theory and network analysis in systems biology. The first lecture describes different types of intracellular networks, methods for constructing biological networks, and different types of graphs used to represent regulatory intracellular networks. The ...

  2. Modeling and analysis of modular structure in diverse biological networks. (United States)

    Al-Anzi, Bader; Gerges, Sherif; Olsman, Noah; Ormerod, Christopher; Piliouras, Georgios; Ormerod, John; Zinn, Kai


    Biological networks, like most engineered networks, are not the product of a singular design but rather are the result of a long process of refinement and optimization. Many large real-world networks are comprised of well-defined and meaningful smaller modules. While engineered networks are designed and refined by humans with particular goals in mind, biological networks are created by the selective pressures of evolution. In this paper, we seek to define aspects of network architecture that are shared among different types of evolved biological networks. First, we developed a new mathematical model, the Stochastic Block Model with Path Selection (SBM-PS) that simulates biological network formation based on the selection of edges that increase clustering. SBM-PS can produce modular networks whose properties resemble those of real networks. Second, we analyzed three real networks of very different types, and showed that all three can be fit well by the SBM-PS model. Third, we showed that modular elements within the three networks correspond to meaningful biological structures. The networks chosen for analysis were a proteomic network composed of all proteins required for mitochondrial function in budding yeast, a mesoscale anatomical network composed of axonal connections among regions of the mouse brain, and the connectome of individual neurons in the nematode C. elegans. We find that the three networks have common architectural features, and each can be divided into subnetworks with characteristic topologies that control specific phenotypic outputs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. SBEToolbox: A Matlab Toolbox for Biological Network Analysis. (United States)

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


    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

  4. Biological Network Inference and analysis using SEBINI and CABIN. (United States)

    Taylor, Ronald; Singhal, Mudita


    Attaining a detailed understanding of the various biological networks in an organism lies at the core of the emerging discipline of systems biology. A precise description of the relationships formed between genes, mRNA molecules, and proteins is a necessary step toward a complete description of the dynamic behavior of an organism at the cellular level, and toward intelligent, efficient, and directed modification of an organism. The importance of understanding such regulatory, signaling, and interaction networks has fueled the development of numerous in silico inference algorithms, as well as new experimental techniques and a growing collection of public databases. The Software Environment for BIological Network Inference (SEBINI) has been created to provide an interactive environment for the deployment, evaluation, and improvement of algorithms used to reconstruct the structure of biological regulatory and interaction networks. SEBINI can be used to analyze high-throughput gene expression, protein abundance, or protein activation data via a suite of state-of-the-art network inference algorithms. It also allows algorithm developers to compare and train network inference methods on artificial networks and simulated gene expression perturbation data. SEBINI can therefore be used by software developers wishing to evaluate, refine, or combine inference techniques, as well as by bioinformaticians analyzing experimental data. Networks inferred from the SEBINI software platform can be further analyzed using the Collective Analysis of Biological Interaction Networks (CABIN) tool, which is an exploratory data analysis software that enables integration and analysis of protein-protein interaction and gene-to-gene regulatory evidence obtained from multiple sources. The collection of edges in a public database, along with the confidence held in each edge (if available), can be fed into CABIN as one "evidence network," using the Cytoscape SIF file format. Using CABIN, one may

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

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima


    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.

  6. Analysis of complex networks from biology to linguistics

    CERN Document Server

    Dehmer, Matthias


    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.

  7. Optimization Techniques for Analysis of Biological and Social Networks (United States)


    This project focused on a multifaceted study of a class of cluster-detection problems arising in biological and social networks . This includes...and heuristics. Originally, clusters (complexes, modules, cohesive subgroups) in biological and social networks were described by cliques (complete

  8. Wavelet analysis of polarization maps of polycrystalline biological fluids networks (United States)

    Ushenko, Y. A.


    The optical model of human joints synovial fluid is proposed. The statistic (statistic moments), correlation (autocorrelation function) and self-similar (Log-Log dependencies of power spectrum) structure of polarization two-dimensional distributions (polarization maps) of synovial fluid has been analyzed. It has been shown that differentiation of polarization maps of joint synovial fluid with different physiological state samples is expected of scale-discriminative analysis. To mark out of small-scale domain structure of synovial fluid polarization maps, the wavelet analysis has been used. The set of parameters, which characterize statistic, correlation and self-similar structure of wavelet coefficients' distributions of different scales of polarization domains for diagnostics and differentiation of polycrystalline network transformation connected with the pathological processes, has been determined.

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

    KAUST Repository

    Haskovec, Jan


    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.

  10. Vicus: Exploiting local structures to improve network-based analysis of biological data.

    Directory of Open Access Journals (Sweden)

    Bo Wang


    Full Text Available Biological networks entail important topological features and patterns critical to understanding interactions within complicated biological systems. Despite a great progress in understanding their structure, much more can be done to improve our inference and network analysis. Spectral methods play a key role in many network-based applications. Fundamental to spectral methods is the Laplacian, a matrix that captures the global structure of the network. Unfortunately, the Laplacian does not take into account intricacies of the network's local structure and is sensitive to noise in the network. These two properties are fundamental to biological networks and cannot be ignored. We propose an alternative matrix Vicus. The Vicus matrix captures the local neighborhood structure of the network and thus is more effective at modeling biological interactions. We demonstrate the advantages of Vicus in the context of spectral methods by extensive empirical benchmarking on tasks such as single cell dimensionality reduction, protein module discovery and ranking genes for cancer subtyping. Our experiments show that using Vicus, spectral methods result in more accurate and robust performance in all of these tasks.

  11. Vicus: Exploiting local structures to improve network-based analysis of biological data. (United States)

    Wang, Bo; Huang, Lin; Zhu, Yuke; Kundaje, Anshul; Batzoglou, Serafim; Goldenberg, Anna


    Biological networks entail important topological features and patterns critical to understanding interactions within complicated biological systems. Despite a great progress in understanding their structure, much more can be done to improve our inference and network analysis. Spectral methods play a key role in many network-based applications. Fundamental to spectral methods is the Laplacian, a matrix that captures the global structure of the network. Unfortunately, the Laplacian does not take into account intricacies of the network's local structure and is sensitive to noise in the network. These two properties are fundamental to biological networks and cannot be ignored. We propose an alternative matrix Vicus. The Vicus matrix captures the local neighborhood structure of the network and thus is more effective at modeling biological interactions. We demonstrate the advantages of Vicus in the context of spectral methods by extensive empirical benchmarking on tasks such as single cell dimensionality reduction, protein module discovery and ranking genes for cancer subtyping. Our experiments show that using Vicus, spectral methods result in more accurate and robust performance in all of these tasks.

  12. Querying Large Biological Network Datasets (United States)

    Gulsoy, Gunhan


    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.…

  13. Synthetic biological networks

    International Nuclear Information System (INIS)

    Archer, Eric; Süel, Gürol M


    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)

  14. Networks in Cell Biology (United States)

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


    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.

  15. Dominating biological networks.

    Directory of Open Access Journals (Sweden)

    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.

  16. NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways (United States)

    Brohée, Sylvain; Faust, Karoline; Lima-Mendez, Gipsi; Sand, Olivier; Janky, Rekin's; Vanderstocken, Gilles; Deville, Yves; van Helden, Jacques


    The network analysis tools (NeAT) ( provide a user-friendly web access to a collection of modular tools for the analysis of networks (graphs) and clusters (e.g. microarray clusters, functional classes, etc.). A first set of tools supports basic operations on graphs (comparison between two graphs, neighborhood of a set of input nodes, path finding and graph randomization). Another set of programs makes the connection between networks and clusters (graph-based clustering, cliques discovery and mapping of clusters onto a network). The toolbox also includes programs for detecting significant intersections between clusters/classes (e.g. clusters of co-expression versus functional classes of genes). NeAT are designed to cope with large datasets and provide a flexible toolbox for analyzing biological networks stored in various databases (protein interactions, regulation and metabolism) or obtained from high-throughput experiments (two-hybrid, mass-spectrometry and microarrays). The web interface interconnects the programs in predefined analysis flows, enabling to address a series of questions about networks of interest. Each tool can also be used separately by entering custom data for a specific analysis. NeAT can also be used as web services (SOAP/WSDL interface), in order to design programmatic workflows and integrate them with other available resources. PMID:18524799

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

    Directory of Open Access Journals (Sweden)

    Astrid eJunker


    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.

  18. Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis. (United States)

    Jabbar-Lopez, Zarif K; Yiu, Zenas Z N; Ward, Victoria; Exton, Lesley S; Mohd Mustapa, M Firouz; Samarasekera, Eleanor; Burden, A David; Murphy, Ruth; Owen, Caroline M; Parslew, Richard; Venning, Vanessa; Warren, Richard B; Smith, Catherine H


    Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3-4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually relevant hubs in biological networks. (United States)

    Muetze, Tanja; Goenawan, Ivan H; Wiencko, Heather L; Bernal-Llinares, Manuel; Bryan, Kenneth; Lynn, David J


    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 (

  20. Biological process linkage networks.

    Directory of Open Access Journals (Sweden)

    Dikla Dotan-Cohen

    Full Text Available The traditional approach to studying complex biological networks is based on the identification of interactions between internal components of signaling or metabolic pathways. By comparison, little is known about interactions between higher order biological systems, such as biological pathways and processes. We propose a methodology for gleaning patterns of interactions between biological processes by analyzing protein-protein interactions, transcriptional co-expression and genetic interactions. At the heart of the methodology are the concept of Linked Processes and the resultant network of biological processes, the Process Linkage Network (PLN.We construct, catalogue, and analyze different types of PLNs derived from different data sources and different species. When applied to the Gene Ontology, many of the resulting links connect processes that are distant from each other in the hierarchy, even though the connection makes eminent sense biologically. Some others, however, carry an element of surprise and may reflect mechanisms that are unique to the organism under investigation. In this aspect our method complements the link structure between processes inherent in the Gene Ontology, which by its very nature is species-independent. As a practical application of the linkage of processes we demonstrate that it can be effectively used in protein function prediction, having the power to increase both the coverage and the accuracy of predictions, when carefully integrated into prediction methods.Our approach constitutes a promising new direction towards understanding the higher levels of organization of the cell as a system which should help current efforts to re-engineer ontologies and improve our ability to predict which proteins are involved in specific biological processes.

  1. Global stability analysis and robust design of multi-time-scale biological networks under parametric uncertainties. (United States)

    Meyer-Baese, Anke; Koshkouei, Ali J; Emmett, Mark R; Goodall, David P


    Biological networks are prone to internal parametric fluctuations and external noises. Robustness represents a crucial property of these networks, which militates the effects of internal fluctuations and external noises. In this paper biological networks are formulated as coupled nonlinear differential systems operating at different time-scales under vanishing perturbations. In contrast to previous work viewing biological parametric uncertain systems as perturbations to a known nominal linear system, the perturbed biological system is modeled as nonlinear perturbations to a known nonlinear idealized system and is represented by two time-scales (subsystems). In addition, conditions for the existence of a global uniform attractor of the perturbed biological system are presented. By using an appropriate Lyapunov function for the coupled system, a maximal upper bound for the fast time-scale associated with the fast state is derived. The proposed robust system design principles are potentially applicable to robust biosynthetic network design. Finally, two examples of two important biological networks, a neural network and a gene regulatory network, are presented to illustrate the applicability of the developed theoretical framework.

  2. 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. (United States)

    Pedersen, Morten Gram


    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.

  3. Design principles in biological networks (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. 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


    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

  5. VAN: an R package for identifying biologically perturbed networks via differential variability analysis


    Jayaswal, Vivek; Schramm, Sarah-Jane; Mann, Graham J; Wilkins, Marc R; Yang, Yee Hwa


    Background Large-scale molecular interaction networks are dynamic in nature and are of special interest in the analysis of complex diseases, which are characterized by network-level perturbations rather than changes in individual genes/proteins. The methods developed for the identification of differentially expressed genes or gene sets are not suitable for network-level analyses. Consequently, bioinformatics approaches that enable a joint analysis of high-throughput transcriptomics datasets a...

  6. Strategic Integration of Multiple Bioinformatics Resources for System Level Analysis of Biological Networks. (United States)

    D'Souza, Mark; Sulakhe, Dinanath; Wang, Sheng; Xie, Bing; Hashemifar, Somaye; Taylor, Andrew; Dubchak, Inna; Conrad Gilliam, T; Maltsev, Natalia


    Recent technological advances in genomics allow the production of biological data at unprecedented tera- and petabyte scales. Efficient mining of these vast and complex datasets for the needs of biomedical research critically depends on a seamless integration of the clinical, genomic, and experimental information with prior knowledge about genotype-phenotype relationships. Such experimental data accumulated in publicly available databases should be accessible to a variety of algorithms and analytical pipelines that drive computational analysis and data mining.We present an integrated computational platform Lynx (Sulakhe et al., Nucleic Acids Res 44:D882-D887, 2016) ( ), a web-based database and knowledge extraction engine. It provides advanced search capabilities and a variety of algorithms for enrichment analysis and network-based gene prioritization. It gives public access to the Lynx integrated knowledge base (LynxKB) and its analytical tools via user-friendly web services and interfaces. The Lynx service-oriented architecture supports annotation and analysis of high-throughput experimental data. Lynx tools assist the user in extracting meaningful knowledge from LynxKB and experimental data, and in the generation of weighted hypotheses regarding the genes and molecular mechanisms contributing to human phenotypes or conditions of interest. The goal of this integrated platform is to support the end-to-end analytical needs of various translational projects.

  7. Insights into TREM2 biology by network analysis of human brain gene expression data. (United States)

    Forabosco, Paola; Ramasamy, Adaikalavan; Trabzuni, Daniah; Walker, Robert; Smith, Colin; Bras, Jose; Levine, Adam P; Hardy, John; Pocock, Jennifer M; Guerreiro, Rita; Weale, Michael E; Ryten, Mina


    Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease. Here we use microarray-based expression data generated from 101 neuropathologically normal individuals and covering 10 brain regions, including the hippocampus, to understand TREM2 biology in human brain. Using network analysis, we detect a highly preserved TREM2-containing module in human brain, show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5 brain regions, including the hippocampus, suggesting that it can drive module function. Using enrichment analysis we show significant overrepresentation of genes implicated in the adaptive and innate immune system. Inspection of genes with the highest connectivity to TREM2 suggests that it plays a key role in mediating changes in the microglial cytoskeleton necessary not only for phagocytosis, but also migration. Most importantly, we show that the TREM2-containing module is significantly enriched for genes genetically implicated in Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia and that among the genes identified are possible new disease-relevant genes. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Sudipta Saha


    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.

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

    DEFF Research Database (Denmark)

    Green, Sara; Serban, Maria; Scholl, Raphael


    The increasing application of network models to interpret biological systems raises a number of important methodological and epistemological questions. What novel insights can network analysis provide in biology? Are network approaches an extension of or in conflict with mechanistic research...

  10. Insights into biological information processing: structural and dynamical analysis of a human protein signalling network

    Energy Technology Data Exchange (ETDEWEB)

    Fuente, Alberto de la; Fotia, Giorgio; Maggio, Fabio; Mancosu, Gianmaria; Pieroni, Enrico [CRS4 Bioinformatica, Parco Tecnologico POLARIS, Ed.1, Loc Piscinamanna, Pula (Italy)], E-mail:


    We present an investigation on the structural and dynamical properties of a 'human protein signalling network' (HPSN). This biological network is composed of nodes that correspond to proteins and directed edges that represent signal flows. In order to gain insight into the organization of cell information processing this network is analysed taking into account explicitly the edge directions. We explore the topological properties of the HPSN at the global and the local scale, further applying the generating function formalism to provide a suitable comparative model. The relationship between the node degrees and the distribution of signals through the network is characterized using degree correlation profiles. Finally, we analyse the dynamical properties of small sub-graphs showing high correlation between their occurrence and dynamic stability.

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

  12. Critical controllability analysis of directed biological networks using efficient graph reduction. (United States)

    Ishitsuka, Masayuki; Akutsu, Tatsuya; Nacher, Jose C


    Network science has recently integrated key concepts from control theory and has applied them to the analysis of the controllability of complex networks. One of the proposed frameworks uses the Minimum Dominating Set (MDS) approach, which has been successfully applied to the identification of cancer-related proteins and in analyses of large-scale undirected networks, such as proteome-wide protein interaction networks. However, many real systems are better represented by directed networks. Therefore, fast algorithms are required for the application of MDS to directed networks. Here, we propose an algorithm that utilises efficient graph reduction to identify critical control nodes in large-scale directed complex networks. The algorithm is 176-fold faster than existing methods and increases the computable network size to 65,000 nodes. We then applied the developed algorithm to metabolic pathways consisting of 70 plant species encompassing major plant lineages ranging from algae to angiosperms and to signalling pathways from C. elegans, D. melanogaster and H. sapiens. The analysis not only identified functional pathways enriched with critical control molecules but also showed that most control categories are largely conserved across evolutionary time, from green algae and early basal plants to modern angiosperm plant lineages.

  13. Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

    Directory of Open Access Journals (Sweden)

    Samra Khalid


    Full Text Available Background Breast cancer (BC is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s. It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α associated Biological Regulatory Network (BRN for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR for wet lab experiments as well as provided valuable insights in the treatment of cancers

  14. Generating confidence intervals on biological networks

    Directory of Open Access Journals (Sweden)

    Stumpf Michael PH


    Full Text Available Abstract Background In the analysis of networks we frequently require the statistical significance of some network statistic, such as measures of similarity for the properties of interacting nodes. The structure of the network may introduce dependencies among the nodes and it will in general be necessary to account for these dependencies in the statistical analysis. To this end we require some form of Null model of the network: generally rewired replicates of the network are generated which preserve only the degree (number of interactions of each node. We show that this can fail to capture important features of network structure, and may result in unrealistic significance levels, when potentially confounding additional information is available. Methods We present a new network resampling Null model which takes into account the degree sequence as well as available biological annotations. Using gene ontology information as an illustration we show how this information can be accounted for in the resampling approach, and the impact such information has on the assessment of statistical significance of correlations and motif-abundances in the Saccharomyces cerevisiae protein interaction network. An algorithm, GOcardShuffle, is introduced to allow for the efficient construction of an improved Null model for network data. Results We use the protein interaction network of S. cerevisiae; correlations between the evolutionary rates and expression levels of interacting proteins and their statistical significance were assessed for Null models which condition on different aspects of the available data. The novel GOcardShuffle approach results in a Null model for annotated network data which appears better to describe the properties of real biological networks. Conclusion An improved statistical approach for the statistical analysis of biological network data, which conditions on the available biological information, leads to qualitatively different results

  15. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions. (United States)

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


    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.

  16. How Scale-Free Are Biological Networks

    NARCIS (Netherlands)

    Khanin, Raya; Wit, Ernst


    The concept of scale-free network has emerged as a powerful unifying paradigm in the study of complex systems in biology and in physical and social studies. Metabolic, protein, and gene interaction networks have been reported to exhibit scale-free behavior based on the analysis of the distribution

  17. Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study.

    Directory of Open Access Journals (Sweden)

    Valborg Gudmundsdottir

    Full Text Available Glucagon-like peptide 1 (GLP-1 stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS of GLP-1 stimulated insulin secretion in non-diabetic individuals from the Netherlands Twin register (n = 126. This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100. Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P < 0.05 with glucose-stimulated insulin secretion phenotypes in up to 5,318 individuals in MAGIC cohorts. The network contains both known and novel genes in the context of insulin secretion and is enriched for members of the focal adhesion, extracellular-matrix receptor interaction, actin cytoskeleton regulation, Rap1 and PI3K-Akt signaling pathways. Adipose tissue is, like the beta-cell, one of the target tissues of GLP-1 and we thus hypothesized that similar networks might be functional in both tissues. In order to verify peripheral effects of GLP-1 stimulation, we compared the transcriptome profiling of ob/ob mice treated with liraglutide, a clinically used GLP-1 receptor agonist, versus baseline controls. Some of the upstream regulators of differentially expressed genes in the white adipose tissue of ob/ob mice were also detected in the human beta-cell network of genes associated with GLP-1 stimulated insulin secretion. The findings provide biological insight into the mechanisms through which the effects of GLP-1 may be modulated and highlight a potential role of the beta-cell expressed genes RYR2, GDI2, KIAA0232, COL4A1 and COL4A2 in GLP-1 stimulated

  18. SEBINI: Software Environment for BIological Network Inference. (United States)

    Taylor, Ronald C; Shah, Anuj; Treatman, Charles; Blevins, Meridith


    The Software Environment for BIological Network Inference (SEBINI) has been created to provide an interactive environment for the deployment and evaluation of algorithms used to reconstruct the structure of biological regulatory and interaction networks. SEBINI can be used to compare and train network inference methods on artificial networks and simulated gene expression perturbation data. It also allows the analysis within the same framework of experimental high-throughput expression data using the suite of (trained) inference methods; hence SEBINI should be useful to software developers wishing to evaluate, compare, refine or combine inference techniques, and to bioinformaticians analyzing experimental data. SEBINI provides a platform that aids in more accurate reconstruction of biological networks, with less effort, in less time. A demonstration website is located at The Java source code and PostgreSQL database schema are available freely for non-commercial use.

  19. Comparative analysis of housekeeping and tissue-selective genes in human based on network topologies and biological properties. (United States)

    Yang, Lei; Wang, Shiyuan; Zhou, Meng; Chen, Xiaowen; Zuo, Yongchun; Sun, Dianjun; Lv, Yingli


    Housekeeping genes are genes that are turned on most of the time in almost every tissue to maintain cellular functions. Tissue-selective genes are predominantly expressed in one or a few biologically relevant tissue types. Benefitting from the massive gene expression microarray data obtained over the past decades, the properties of housekeeping and tissue-selective genes can now be investigated on a large-scale manner. In this study, we analyzed the topological properties of housekeeping and tissue-selective genes in the protein-protein interaction (PPI) network. Furthermore, we compared the biological properties and amino acid usage between these two gene groups. The results indicated that there were significant differences in topological properties between housekeeping and tissue-selective genes in the PPI network, and housekeeping genes had higher centrality properties and may play important roles in the complex biological network environment. We also found that there were significant differences in multiple biological properties and many amino acid compositions. The functional genes enrichment and subcellular localizations analysis was also performed to investigate the characterization of housekeeping and tissue-selective genes. The results indicated that the two gene groups showed significant different enrichment in drug targets, disease genes and toxin targets, and located in different subcellular localizations. At last, the discriminations between the properties of two gene groups were measured by the F-score, and expression stage had the most discriminative index in all properties. These findings may elucidate the biological mechanisms for understanding housekeeping and tissue-selective genes and may contribute to better annotate housekeeping and tissue-selective genes in other organisms.

  20. Biological network analysis with CentiScaPe: centralities and experimental dataset integration [v2; ref status: indexed,

    Directory of Open Access Journals (Sweden)

    Giovanni Scardoni


    Full Text Available The growing dimension and complexity of the available experimental data generating biological networks have increased the need for tools that help in categorizing nodes by their topological relevance. Here we present CentiScaPe, a Cytoscape app specifically designed to calculate centrality indexes used for the identification of the most important nodes in a network. CentiScaPe is a comprehensive suite of algorithms dedicated to network nodes centrality analysis, computing several centralities for undirected, directed and weighted networks. The results of the topological analysis can be integrated with data set from lab experiments, like expression or phosphorylation levels for each protein represented in the network. Our app opens new perspectives in the analysis of biological networks, since the integration of topological analysis with lab experimental data enhance the predictive power of the bioinformatics analysis.

  1. Network biology methods integrating biological data for translational science. (United States)

    Bebek, Gurkan; Koyutürk, Mehmet; Price, Nathan D; Chance, Mark R


    The explosion of biomedical data, both on the genomic and proteomic side as well as clinical data, will require complex integration and analysis to provide new molecular variables to better understand the molecular basis of phenotype. Currently, much data exist in silos and is not analyzed in frameworks where all data are brought to bear in the development of biomarkers and novel functional targets. This is beginning to change. Network biology approaches, which emphasize the interactions between genes, proteins and metabolites provide a framework for data integration such that genome, proteome, metabolome and other -omics data can be jointly analyzed to understand and predict disease phenotypes. In this review, recent advances in network biology approaches and results are identified. A common theme is the potential for network analysis to provide multiplexed and functionally connected biomarkers for analyzing the molecular basis of disease, thus changing our approaches to analyzing and modeling genome- and proteome-wide data.

  2. Dense module enumeration in biological networks

    International Nuclear Information System (INIS)

    Tsuda, Koji; Georgii, Elisabeth


    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.

  3. Adverse effects of biologics: a network meta-analysis and Cochrane overview

    DEFF Research Database (Denmark)

    Singh, J. A.; Wells, G. A.; Christensen, Robin Daniel Kjersgaard


    Background Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious...... results We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group...

  4. Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study

    DEFF Research Database (Denmark)

    Gudmundsdottir, Valborg; Pedersen, Helle Krogh; Allebrandt, Karla Viviani


    cohorts. The network contains both known and novel genes in the context of insulin secretion and is enriched for members of the focal adhesion, extracellular-matrix receptor interaction, actin cytoskeleton regulation, Rap1 and PI3K-Akt signaling pathways. Adipose tissue is, like the beta-cell, one...

  5. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis. (United States)

    Singh, Jasvinder A; Hossain, Alomgir; Mudano, Amy S; Tanjong Ghogomu, Elizabeth; Suarez-Almazor, Maria E; Buchbinder, Rachelle; Maxwell, Lara J; Tugwell, Peter; Wells, George A


    Biologic disease-modifying anti-rheumatic drugs (biologics) are highly effective in treating rheumatoid arthritis (RA), however there are few head-to-head biologic comparison studies. We performed a systematic review, a standard meta-analysis and a network meta-analysis (NMA) to update the 2009 Cochrane Overview. This review is focused on the adults with RA who are naive to methotrexate (MTX) that is, receiving their first disease-modifying agent. To compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib versus comparator (methotrexate (MTX)/other DMARDs) in people with RA who are naive to methotrexate. In June 2015 we searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE and Embase; and trials registers. We used standard Cochrane methods. We calculated odds ratios (OR) and mean differences (MD) along with 95% confidence intervals (CI) for traditional meta-analyses and 95% credible intervals (CrI) using a Bayesian mixed treatment comparisons approach for network meta-analysis (NMA). We converted OR to risk ratios (RR) for ease of interpretation. We also present results in absolute measures as risk difference (RD) and number needed to treat for an additional beneficial or harmful outcome (NNTB/H). Nineteen RCTs with 6485 participants met inclusion criteria (including five studies from the original 2009 review), and data were available for four TNF biologics (adalimumab (six studies; 1851 participants), etanercept (three studies; 678 participants), golimumab (one study; 637 participants) and infliximab (seven studies; 1363 participants)) and two non-TNF biologics (abatacept (one study; 509 participants) and rituximab (one study; 748 participants)).Less than 50% of the studies were judged to be at low risk of bias for allocation sequence generation, allocation concealment and blinding, 21% were at low risk for selective

  6. A canonical correlation analysis-based dynamic bayesian network prior to infer gene regulatory networks from multiple types of biological data. (United States)

    Baur, Brittany; Bozdag, Serdar


    One of the challenging and important computational problems in systems biology is to infer gene regulatory networks (GRNs) of biological systems. Several methods that exploit gene expression data have been developed to tackle this problem. In this study, we propose the use of copy number and DNA methylation data to infer GRNs. We developed an algorithm that scores regulatory interactions between genes based on canonical correlation analysis. In this algorithm, copy number or DNA methylation variables are treated as potential regulator variables, and expression variables are treated as potential target variables. We first validated that the canonical correlation analysis method is able to infer true interactions in high accuracy. We showed that the use of DNA methylation or copy number datasets leads to improved inference over steady-state expression. Our results also showed that epigenetic and structural information could be used to infer directionality of regulatory interactions. Additional improvements in GRN inference can be gleaned from incorporating the result in an informative prior in a dynamic Bayesian algorithm. This is the first study that incorporates copy number and DNA methylation into an informative prior in dynamic Bayesian framework. By closely examining top-scoring interactions with different sources of epigenetic or structural information, we also identified potential novel regulatory interactions.

  7. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena


    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 ...

  8. Invasion exponents in biological networks (United States)

    Demetrius, Lloyd; Gundlach, Volker Matthias; Ochs, Gunter


    This article is concerned with the characterization of invasion exponents in biological networks defined by a population of replicating elements: molecules, cells, higher organisms. We show that the outcome of competition between an invader and a resident population is a stochastic process, determined by the rate at which a population returns to its steady state after a random perturbation in the parameters that characterize the replicating elements. This return rate is defined by the macroscopic parameter evolutionary entropy, a measure of the diversity of the interaction between the individuals in the population. We also show that the evolutionary stability of a population, that is the invulnerability of a resident to the introduction of an invader competing for the available resources, are given by extremal states of entropy. These results which pertain to networks of interacting molecules, cells and higher organisms, are generalizations of results established for demographic networks, that is populations of replicating organisms parametrized by the ages at which they reproduce and die.

  9. Social traits, social networks and evolutionary biology. (United States)

    Fisher, D N; McAdam, A G


    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.

  10. Biological transportation networks: Modeling and simulation

    KAUST Repository

    Albi, Giacomo


    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.

  11. Novel topological descriptors for analyzing biological networks

    Directory of Open Access Journals (Sweden)

    Varmuza Kurt K


    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.

  12. A generic algorithm for layout of biological networks. (United States)

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


    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.

  13. A generic algorithm for layout of biological networks

    Directory of Open Access Journals (Sweden)

    Dwyer Tim


    Full Text Available Abstract Background 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. Results 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. Conclusion 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.

  14. Continuum Modeling of Biological Network Formation

    KAUST Repository

    Albi, Giacomo


    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.

  15. Measuring the evolutionary rewiring of biological networks.

    Directory of Open Access Journals (Sweden)

    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.

  16. Mango: combining and analyzing heterogeneous biological networks. (United States)

    Chang, Jennifer; Cho, Hyejin; Chou, Hui-Hsien


    Heterogeneous biological data such as sequence matches, gene expression correlations, protein-protein interactions, and biochemical pathways can be merged and analyzed via graphs, or networks. Existing software for network analysis has limited scalability to large data sets or is only accessible to software developers as libraries. In addition, the polymorphic nature of the data sets requires a more standardized method for integration and exploration. Mango facilitates large network analyses with its Graph Exploration Language, automatic graph attribute handling, and real-time 3-dimensional visualization. On a personal computer Mango can load, merge, and analyze networks with millions of links and can connect to online databases to fetch and merge biological pathways. Mango is written in C++ and runs on Mac OS, Windows, and Linux. The stand-alone distributions, including the Graph Exploration Language integrated development environment, are freely available for download from The Mango User Guide listing all features can be found at

  17. 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.

  18. Correlation-Based Network Generation, Visualization, and Analysis as a Powerful Tool in Biological Studies: A Case Study in Cancer Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Albert Batushansky


    Full Text Available In the last decade vast data sets are being generated in biological and medical studies. The challenge lies in their summary, complexity reduction, and interpretation. Correlation-based networks and graph-theory based properties of this type of networks can be successfully used during this process. However, the procedure has its pitfalls and requires specific knowledge that often lays beyond classical biology and includes many computational tools and software. Here we introduce one of a series of methods for correlation-based network generation and analysis using freely available software. The pipeline allows the user to control each step of the network generation and provides flexibility in selection of correlation methods and thresholds. The pipeline was implemented on published metabolomics data of a population of human breast carcinoma cell lines MDA-MB-231 under two conditions: normal and hypoxia. The analysis revealed significant differences between the metabolic networks in response to the tested conditions. The network under hypoxia had 1.7 times more significant correlations between metabolites, compared to normal conditions. Unique metabolic interactions were identified which could lead to the identification of improved markers or aid in elucidating the mechanism of regulation between distantly related metabolites induced by the cancer growth.

  19. Communication on the structure of biological networks

    Indian Academy of Sciences (India)

    An epidemic can also spread faster in neuronal networks than in the other biological networks studied here. Thus, the underlying undirected architecture of a neuronal network possesses certain conformation which is favourable for spreading different entities or information. Now, to explore the topological characteristics that ...

  20. Network Reconstruction of Dynamic Biological Systems


    Asadi, Behrang


    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...

  1. Ontology- and graph-based similarity assessment in biological networks. (United States)

    Wang, Haiying; Zheng, Huiru; Azuaje, Francisco


    A standard systems-based approach to biomarker and drug target discovery consists of placing putative biomarkers in the context of a network of biological interactions, followed by different 'guilt-by-association' analyses. The latter is typically done based on network structural features. Here, an alternative analysis approach in which the networks are analyzed on a 'semantic similarity' space is reported. Such information is extracted from ontology-based functional annotations. We present SimTrek, a Cytoscape plugin for ontology-based similarity assessment in biological networks. Supplementary data are available at Bioinformatics online.

  2. Contextual Hub Analysis Tool (CHAT: A Cytoscape app for identifying contextually relevant hubs in biological networks [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Tanja Muetze


    Full Text Available 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.   Availability: CHAT is available for Cytoscape 3.0+ and can be installed via the Cytoscape App Store (

  3. Communication on the structure of biological networks

    Indian Academy of Sciences (India)

    As there is an interplay between network architecture and dynamics, structure plays an important role in communication and spreading of information in a network. ... Department of Mathematics and Statistics, Indian Institute of Science Education and Research Kolkata, Mohanpur 741 246, India; Department of Biological ...

  4. Communication on the structure of biological networks

    Indian Academy of Sciences (India)

    from five different classes (neuronal, food web, protein–protein interaction, metabolism and gene regulation) and ..... food webs show good expansion property (see table 1) unlike other biological networks. The distribution of distances ..... tion is very fast on a network having high degree nodes. Later on, it was shown that.

  5. Network-Based Models in Molecular Biology (United States)

    Beyer, Andreas

    Biological systems are characterized by a large number of diverse interactions. Interaction maps have been used to abstract those interactions at all biological scales ranging from food webs at the ecosystem level down to protein interaction networks at the molecular scale.

  6. Metannogen: annotation of biological reaction networks. (United States)

    Gille, Christoph; Hübner, Katrin; Hoppe, Andreas; Holzhütter, Hermann-Georg


    Semantic annotations of the biochemical entities constituting a biological reaction network are indispensable to create biologically meaningful networks. They further heighten efficient exchange, reuse and merging of existing models which concern present-day systems biology research more often. Two types of tools for the reconstruction of biological networks currently exist: (i) several sophisticated programs support graphical network editing and visualization. (ii) Data management systems permit reconstruction and curation of huge networks in a team of scientists including data integration, annotation and cross-referencing. We seeked ways to combine the advantages of both approaches. Metannogen, which was previously developed for network reconstruction, has been considerably improved. From now on, Metannogen provides sbml import and annotation of networks created elsewhere. This permits users of other network reconstruction platforms or modeling software to annotate their networks using Metannogen's advanced information management. We implemented word-autocompletion, multipattern highlighting, spell check, brace-expansion and publication management, and improved annotation, cross-referencing and team work requirements. Unspecific enzymes and transporters acting on a spectrum of different substrates are efficiently handled. The network can be exported in sbml format where the annotations are embedded in line with the miriam standard. For more comfort, Metannogen may be tightly coupled with the network editor such that Metannogen becomes an additional view for the focused reaction in the network editor. Finally, Metannogen provides local single user, shared password protected multiuser or public access to the annotation data. Metannogen is available free of charge at: or Supplementary data are available at Bioinformatics online.

  7. Cytoscape ESP: simple search of complex biological networks. (United States)

    Ashkenazi, Maital; Bader, Gary D; Kuchinsky, Allan; Moshelion, Menachem; States, David J


    Cytoscape enhanced search plugin (ESP) enables searching complex biological networks on multiple attribute fields using logical operators and wildcards. Queries use an intuitive syntax and simple search line interface. ESP is implemented as a Cytoscape plugin and complements existing search functions in the Cytoscape network visualization and analysis software, allowing users to easily identify nodes, edges and subgraphs of interest, even for very large networks. Availabiity:

  8. Controllability and observability of Boolean networks arising from biology (United States)

    Li, Rui; Yang, Meng; Chu, Tianguang


    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.

  9. Predicting biological networks from genomic data

    DEFF Research Database (Denmark)

    Harrington, Eoghan D; Jensen, Lars J; Bork, Peer


    Continuing improvements in DNA sequencing technologies are providing us with vast amounts of genomic data from an ever-widening range of organisms. The resulting challenge for bioinformatics is to interpret this deluge of data and place it back into its biological context. Biological networks...... provide a conceptual framework with which we can describe part of this context, namely the different interactions that occur between the molecular components of a cell. Here, we review the computational methods available to predict biological networks from genomic sequence data and discuss how they relate...

  10. C. elegans network biology: a beginning. (United States)

    Piano, Fabio; Gunsalus, Kristin C; Hill, David E; Vidal, Marc


    The architecture and dynamics of molecular networks can provide an understanding of complex biological processes complementary to that obtained from the in-depth study of single genes and proteins. With a completely sequenced and well-annotated genome, a fully characterized cell lineage, and powerful tools available to dissect development, Caenorhabditis elegans, among metazoans, provides an optimal system to bridge cellular and organismal biology with the global properties of macromolecular networks. This chapter considers omic technologies available for C. elegans to describe molecular networks--encompassing transcriptional and phenotypic profiling as well as physical interaction mapping--and discusses how their individual and integrated applications are paving the way for a network-level understanding of C. elegans biology.

  11. Quantifying evolvability in small biological networks

    Energy Technology Data Exchange (ETDEWEB)

    Nemenman, Ilya [Los Alamos National Laboratory; Mugler, Andrew [COLUMBIA UNIV; Ziv, Etay [COLUMBIA UNIV; Wiggins, Chris H [COLUMBIA UNIV


    The authors introduce a quantitative measure of the capacity of a small biological network to evolve. The measure is applied to a stochastic description of the experimental setup of Guet et al. (Science 2002, 296, pp. 1466), treating chemical inducers as functional inputs to biochemical networks and the expression of a reporter gene as the functional output. The authors take an information-theoretic approach, allowing the system to set parameters that optimise signal processing ability, thus enumerating each network's highest-fidelity functions. All networks studied are highly evolvable by the measure, meaning that change in function has little dependence on change in parameters. Moreover, each network's functions are connected by paths in the parameter space along which information is not significantly lowered, meaning a network may continuously change its functionality without completely losing it along the way. This property further underscores the evolvability of the networks.

  12. Ultraperformance liquid chromatography-mass spectrometry based comprehensive metabolomics combined with pattern recognition and network analysis methods for characterization of metabolites and metabolic pathways from biological data sets. (United States)

    Zhang, Ai-hua; Sun, Hui; Han, Ying; Yan, Guang-li; Yuan, Ye; Song, Gao-chen; Yuan, Xiao-xia; Xie, Ning; Wang, Xi-jun


    Metabolomics is the study of metabolic changes in biological systems and provides the small molecule fingerprints related to the disease. Extracting biomedical information from large metabolomics data sets by multivariate data analysis is of considerable complexity. Therefore, more efficient and optimizing metabolomics data processing technologies are needed to improve mass spectrometry applications in biomarker discovery. Here, we report the findings of urine metabolomic investigation of hepatitis C virus (HCV) patients by high-throughput ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) coupled with pattern recognition methods (principal component analysis, partial least-squares, and OPLS-DA) and network pharmacology. A total of 20 urinary differential metabolites (13 upregulated and 7 downregulated) were identified and contributed to HCV progress, involve several key metabolic pathways such as taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, histidine metabolism, arginine and proline metabolism, and so forth. Metabolites identified through metabolic profiling may facilitate the development of more accurate marker algorithms to better monitor disease progression. Network analysis validated close contact between these metabolites and implied the importance of the metabolic pathways. Mapping altered metabolites to KEGG pathways identified alterations in a variety of biological processes mediated through complex networks. These findings may be promising to yield a valuable and noninvasive tool that insights into the pathophysiology of HCV and to advance the early diagnosis and monitor the progression of disease. Overall, this investigation illustrates the power of the UPLC-MS platform combined with the pattern recognition and network analysis methods that can engender new insights into HCV pathobiology.

  13. Exploring biological network structure with clustered random networks

    Directory of Open Access Journals (Sweden)

    Bansal Shweta


    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

  14. Discriminative topological features reveal biological network mechanisms

    Directory of Open Access Journals (Sweden)

    Levovitz Chaya


    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.

  15. 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.

  16. 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)


    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.

  17. 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. (United States)

    Jalili, Mahdi


    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.

  18. Network biology concepts in complex disease comorbidities

    DEFF Research Database (Denmark)

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


    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...

  19. Asymmetric Branching in Biological Resource Distribution Networks (United States)

    Brummer, Alexander Byers

    There is a remarkable relationship between an organism's metabolic rate (resting power consumption) and the organism's mass. It may be a universal law of nature that an organism's resting metabolic rate is proportional to its mass to the power of 3/4. This relationship, known as Kleiber's Law, appears to be valid for both plants and animals. This law is important because it implies that larger organisms are more efficient than smaller organisms, and knowledge regarding metabolic rates are essential to a multitude of other fields in ecology and biology. This includes modeling the interactions of many species across multiple trophic levels, distributions of species abundances across large spatial landscapes, and even medical diagnostics for respiratory and cardiovascular pathologies. Previous models of vascular networks that seek to identify the origin of metabolic scaling have all been based on the unrealistic assumption of perfectly symmetric branching. In this dissertation I will present a theory of asymmetric branching in self-similar vascular networks (published by Brummer et al. in [9]). The theory shows that there can exist a suite of vascular forms that result in the often observed 3/4 metabolic scaling exponent of Kleiber's Law. Furthermore, the theory makes predictions regarding major morphological features related to vascular branching patterns and their relationships to metabolic scaling. These predictions are suggestive of evolutionary convergence in vascular branching. To test these predictions, I will present an analysis of real mammalian and plant vascular data that shows: (i) broad patterns in vascular networks across entire animal kingdoms and (ii) within these patterns, plant and mammalian vascular networks can be uniquely distinguished from one another (publication in preparation by Brummer et al.). I will also present results from a computational study in support of point (i). Namely, that asymmetric branching may be the optimal strategy to

  20. Discovery of Chemical Toxicity via Biological Networks and Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Edward; Habib, Tanwir; Guan, Xin; Escalon, Barbara; Falciani, Francesco; Chipman, J.K.; Antczak, Philipp; Edwards, Stephen; Taylor, Ronald C.; Vulpe, Chris; Loguinov, Alexandre; Van Aggelen, Graham; Villeneuve, Daniel L.; Garcia-Reyero, Natalia


    Both soldiers and animals are exposed to many chemicals as the result of military activities. Tools are needed to understand the hazards and risks that chemicals and new materials pose to soldiers and the environment. We have investigated the potential of global gene regulatory networks in understanding the impact of chemicals on reproduction. We characterized effects of chemicals on ovaries of the model animal system, the Fathead minnow (Pimopheles promelas) connecting chemical impacts on gene expression to circulating blood levels of the hormones testosterone and estradiol in addition to the egg yolk protein vitellogenin. We describe the application of reverse engineering complex interaction networks from high dimensional gene expression data to characterize chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis that governs reproduction in fathead minnows. The construction of global gene regulatory networks provides deep insights into how drugs and chemicals effect key organs and biological pathways.

  1. Integrative network biology: graph prototyping for co-expression cancer networks.

    Directory of Open Access Journals (Sweden)

    Karl G Kugler

    Full Text Available Network-based analysis has been proven useful in biologically-oriented areas, e.g., to explore the dynamics and complexity of biological networks. Investigating a set of networks allows deriving general knowledge about the underlying topological and functional properties. The integrative analysis of networks typically combines networks from different studies that investigate the same or similar research questions. In order to perform an integrative analysis it is often necessary to compare the properties of matching edges across the data set. This identification of common edges is often burdensome and computational intensive. Here, we present an approach that is different from inferring a new network based on common features. Instead, we select one network as a graph prototype, which then represents a set of comparable network objects, as it has the least average distance to all other networks in the same set. We demonstrate the usefulness of the graph prototyping approach on a set of prostate cancer networks and a set of corresponding benign networks. We further show that the distances within the cancer group and the benign group are statistically different depending on the utilized distance measure.

  2. Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

    Directory of Open Access Journals (Sweden)

    Adrian D Vickers

    Full Text Available Biological therapies are increasingly used to treat ulcerative colitis (UC.To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF therapy.A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance.Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI]: 2.19 [1.35-3.55], clinical remission (OR [95% CrI]: 2.81 [1.49-5.49], and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]; there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]. In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0].This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All

  3. Logical analysis of biological systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian


    R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005.......R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005....

  4. Review of Biological Network Data and Its Applications

    Directory of Open Access Journals (Sweden)

    Donghyeon Yu


    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.

  5. Emergence of communication in socio-biological networks

    CERN Document Server

    Berea, Anamaria


    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 ...

  6. Applying differential dynamic logic to reconfigurable biological networks. (United States)

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


    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.

  7. PANET: a GPU-based tool for fast parallel analysis of robustness dynamics and feed-forward/feedback loop structures in large-scale biological networks.

    Directory of Open Access Journals (Sweden)

    Hung-Cuong Trinh

    Full Text Available It has been a challenge in systems biology to unravel relationships between structural properties and dynamic behaviors of biological networks. A Cytoscape plugin named NetDS was recently proposed to analyze the robustness-related dynamics and feed-forward/feedback loop structures of biological networks. Despite such a useful function, limitations on the network size that can be analyzed exist due to high computational costs. In addition, the plugin cannot verify an intrinsic property which can be induced by an observed result because it has no function to simulate the observation on a large number of random networks. To overcome these limitations, we have developed a novel software tool, PANET. First, the time-consuming parts of NetDS were redesigned to be processed in parallel using the OpenCL library. This approach utilizes the full computing power of multi-core central processing units and graphics processing units. Eventually, this made it possible to investigate a large-scale network such as a human signaling network with 1,609 nodes and 5,063 links. We also developed a new function to perform a batch-mode simulation where it generates a lot of random networks and conducts robustness calculations and feed-forward/feedback loop examinations of them. This helps us to determine if the findings in real biological networks are valid in arbitrary random networks or not. We tested our plugin in two case studies based on two large-scale signaling networks and found interesting results regarding relationships between coherently coupled feed-forward/feedback loops and robustness. In addition, we verified whether or not those findings are consistently conserved in random networks through batch-mode simulations. Taken together, our plugin is expected to effectively investigate various relationships between dynamics and structural properties in large-scale networks. Our software tool, user manual and example datasets are freely available at

  8. Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data. (United States)

    McWilliams, Daniel F; Ferguson, Eamonn; Young, Adam; Kiely, Patrick D W; Walsh, David A


    Rheumatoid arthritis (RA) disease activity is often measured using the 28-joint Disease Activity Score (DAS28). We aimed to identify and independently verify subgroups of people with RA that may be discordant with respect to self-reported and objective disease state, with potentially different clinical needs. Data were derived from three cohorts: (1) the Early Rheumatoid Arthritis Network (ERAN) and the British Society for Rheumatology Biologics Register (BSRBR), (2) those commencing tumour necrosis factor (TNF)-α inhibitors and (3) those using non-biologic drugs. In latent class analysis, we used variables related to pain, central pain mechanisms or inflammation (pain, vitality, mental health, erythrocyte sedimentation rate, swollen joint count, tender joint count, visual analogue scale of general health). Clinically relevant outcomes were examined. Five, four and four latent classes were found in the ERAN, BSRBR TNF inhibitor and non-biologic cohorts, respectively. The proportions of people assigned with >80% probability into latent classes were 76%, 58% and 72% in the ERAN, TNF inhibitor and non-biologic cohorts, respectively. The latent classes displayed either concordance between measures indicative of mild, moderate or severe disease activity; discordantly worse patient-reported measures despite less markedly elevated inflammation; or discordantly less severe patient-reported measures despite elevated inflammation. Latent classes with discordantly worse patient-reported measures represented 12%, 40% and 21% of the ERAN, TNF inhibitor and non-biologic cohorts, respectively; contained more females; and showed worse function. In those latent classes with worse scores at baseline, DAS28 and function improved over 1 year (p pain management strategies.

  9. Analysis of the text of a textbook of biology oriented by actor-network theory: a study on the theme “biological evolution”

    Directory of Open Access Journals (Sweden)

    Francisco Ângelo Coutinho


    Full Text Available In this paper we present a strategy for analyzing the text of the textbook based on principles of Actor-Network Theory. This theory seeks to understand central claims about knowledge, subjectivity, society and nature, as effects of an interaction network. By analyzing the argumentative strategies employed by the authors of the text analyzed, we found that there is a process of strengthening the scientific explanation that construct a conception of science and which leaves religious conceptions isolated. In this process, the authors establish a network that exclude religious explanation of the field of rationality and interdict the rationality of religion. We wondered whether this is the best attitude when considering the diversity present in school.

  10. Classification of the micro and nanoparticles and biological agents by neural network analysis of the parameters of optical resonance of whispering gallery mode in dielectric microspheres (United States)

    Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schweiger, Gustav; Ostendorf, Andreas


    A novel technique for the label-free analysis of micro and nanoparticles including biomolecules using optical micro cavity resonance of whispering-gallery-type modes is being developed. Various schemes of the method using both standard and specially produced microspheres have been investigated to make further development for microbial application. It was demonstrated that optical resonance under optimal geometry could be detected under the laser power of less 1 microwatt. The sensitivity of developed schemes has been tested by monitoring the spectral shift of the whispering gallery modes. Water solutions of ethanol, ascorbic acid, blood phantoms including albumin and HCl, glucose, biotin, biomarker like C reactive protein so as bacteria and virus phantoms (gels of silica micro and nanoparticles) have been used. Structure of resonance spectra of the solutions was a specific subject of investigation. Probabilistic neural network classifier for biological agents and micro/nano particles classification has been developed. Several parameters of resonance spectra as spectral shift, broadening, diffuseness and others have been used as input parameters to develop a network classifier for micro and nanoparticles and biological agents in solution. Classification probability of approximately 98% for probes under investigation have been achieved. Developed approach have been demonstrated to be a promising technology platform for sensitive, lab-on-chip type sensor which can be used for development of diagnostic tools for different biological molecules, e.g. proteins, oligonucleotides, oligosaccharides, lipids, small molecules, viral particles, cells as well as in different experimental contexts e.g. proteomics, genomics, drug discovery, and membrane studies.

  11. Bayesian Network Webserver: a comprehensive tool for biological network modeling. (United States)

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


    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 (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). Supplementary data are available at Bioinformatics online.

  12. Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis. (United States)

    Reyes-Gibby, Cielito C; Melkonian, Stephanie C; Wang, Jian; Yu, Robert K; Shelburne, Samuel A; Lu, Charles; Gunn, Gary Brandon; Chambers, Mark S; Hanna, Ehab Y; Yeung, Sai-Ching J; Shete, Sanjay


    Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06-08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological

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

    Directory of Open Access Journals (Sweden)

    Jacques Demongeot


    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.

  14. PREMER: a Tool to Infer Biological Networks. (United States)

    Villaverde, Alejandro F; Becker, Kolja; Banga, Julio R


    Inferring the structure of unknown cellular networks is a main challenge in computational biology. Data-driven approaches based on information theory can determine the existence of interactions among network nodes automatically. However, the elucidation of certain features - such as distinguishing between direct and indirect interactions or determining the direction of a causal link - requires estimating information-theoretic quantities in a multidimensional space. This can be a computationally demanding task, which acts as a bottleneck for the application of elaborate algorithms to large-scale network inference problems. The computational cost of such calculations can be alleviated by the use of compiled programs and parallelization. To this end we have developed PREMER (Parallel Reverse Engineering with Mutual information & Entropy Reduction), a software toolbox that can run in parallel and sequential environments. It uses information theoretic criteria to recover network topology and determine the strength and causality of interactions, and allows incorporating prior knowledge, imputing missing data, and correcting outliers. PREMER is a free, open source software tool that does not require any commercial software. Its core algorithms are programmed in FORTRAN 90 and implement OpenMP directives. It has user interfaces in Python and MATLAB/Octave, and runs on Windows, Linux and OSX (

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

    Directory of Open Access Journals (Sweden)

    Kormeier Benjamin


    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.

  16. Noncommutative Biology: Sequential Regulation of Complex Networks.

    Directory of Open Access Journals (Sweden)

    William Letsou


    Full Text Available Single-cell variability in gene expression is important for generating distinct cell types, but it is unclear how cells use the same set of regulatory molecules to specifically control similarly regulated genes. While combinatorial binding of transcription factors at promoters has been proposed as a solution for cell-type specific gene expression, we found that such models resulted in substantial information bottlenecks. We sought to understand the consequences of adopting sequential logic wherein the time-ordering of factors informs the final outcome. We showed that with noncommutative control, it is possible to independently control targets that would otherwise be activated simultaneously using combinatorial logic. Consequently, sequential logic overcomes the information bottleneck inherent in complex networks. We derived scaling laws for two noncommutative models of regulation, motivated by phosphorylation/neural networks and chromosome folding, respectively, and showed that they scale super-exponentially in the number of regulators. We also showed that specificity in control is robust to the loss of a regulator. Lastly, we connected these theoretical results to real biological networks that demonstrate specificity in the context of promiscuity. These results show that achieving a desired outcome often necessitates roundabout steps.

  17. Harnessing systems biology approaches to engineer functional microvascular networks. (United States)

    Sefcik, Lauren S; Wilson, Jennifer L; Papin, Jason A; Botchwey, Edward A


    Microvascular remodeling is a complex process that includes many cell types and molecular signals. Despite a continued growth in the understanding of signaling pathways involved in the formation and maturation of new blood vessels, approximately half of all compounds entering clinical trials will fail, resulting in the loss of much time, money, and resources. Most pro-angiogenic clinical trials to date have focused on increasing neovascularization via the delivery of a single growth factor or gene. Alternatively, a focus on the concerted regulation of whole networks of genes may lead to greater insight into the underlying physiology since the coordinated response is greater than the sum of its parts. Systems biology offers a comprehensive network view of the processes of angiogenesis and arteriogenesis that might enable the prediction of drug targets and whether or not activation of the targets elicits the desired outcome. Systems biology integrates complex biological data from a variety of experimental sources (-omics) and analyzes how the interactions of the system components can give rise to the function and behavior of that system. This review focuses on how systems biology approaches have been applied to microvascular growth and remodeling, and how network analysis tools can be utilized to aid novel pro-angiogenic drug discovery.


    Directory of Open Access Journals (Sweden)

    Eduardo Fonseca-Pedrero


    Full Text Available The main goal of this work is to introduce a new approach called network analysis for its application in the field of psychology. In this paper we present the network model in a brief, entertaining and simple way and, as far as possible, away from technicalities and the statistical point of view. The aim of this outline is, on the one hand, to take the first steps in network analysis, and on the other, to show the theoretical and clinical implications underlying this model. Firstly, the roots of this approach are discussed as well as its way of understanding psychological phenomena, specifically psychopathological problems. The concepts of network, node and edge, the types of networks and the procedures for their estimation are all addressed. Next, measures of centrality are explained and some applications in the field of psychology are mentioned. Later, this approach is exemplified with a specific case, which estimates and analyzes a network of personality traits within the Big Five model. The syntax of this analysis is provided. Finally, by way of conclusion, a brief recapitulation is provided, and some cautionary reflections and future research lines are discussed.

  19. Biological sequence analysis

    DEFF Research Database (Denmark)

    Durbin, Richard; Eddy, Sean; Krogh, Anders Stærmose

    This book provides an up-to-date and tutorial-level overview of sequence analysis methods, with particular emphasis on probabilistic modelling. Discussed methods include pairwise alignment, hidden Markov models, multiple alignment, profile searches, RNA secondary structure analysis, and phylogene......This book provides an up-to-date and tutorial-level overview of sequence analysis methods, with particular emphasis on probabilistic modelling. Discussed methods include pairwise alignment, hidden Markov models, multiple alignment, profile searches, RNA secondary structure analysis...

  20. Static Analysis for Systems Biology

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nielson, Hanne Riis; Rosa, D. Schuch da


    This paper shows how static analysis techniques can help understanding biological systems. Based on a simple example we illustrate the outcome of performing three different analyses extracting information of increasing precision. We conclude by reporting on the potential impact and exploitation o...... of these techniques in systems biology....

  1. Toward Synthetic Biology Strategies for Adipic Acid Production: An in Silico Tool for Combined Thermodynamics and Stoichiometric Analysis of Metabolic Networks. (United States)

    Averesch, Nils J H; Martínez, Verónica S; Nielsen, Lars K; Krömer, Jens O


    Adipic acid, a nylon-6,6 precursor, has recently gained popularity in synthetic biology. Here, 16 different production routes to adipic acid were evaluated using a novel tool for network-embedded thermodynamic analysis of elementary flux modes. The tool distinguishes between thermodynamically feasible and infeasible modes under determined metabolite concentrations, allowing the thermodynamic feasibility of theoretical yields to be assessed. Further, patterns that always caused infeasible flux distributions were identified, which will aid the development of tailored strain design. A review of cellular efflux mechanisms revealed that significant accumulation of extracellular product is only possible if coupled with ATP hydrolysis. A stoichiometric analysis demonstrated that the maximum theoretical product carbon yield heavily depends on the metabolic route, ranging from 32 to 99% on glucose and/or palmitate in Escherichia coli and Saccharomyces cerevisiae metabolic models. Equally important, metabolite concentrations appeared to be thermodynamically restricted in several pathways. Consequently, the number of thermodynamically feasible flux distributions was reduced, in some cases even rendering whole pathways infeasible, highlighting the importance of pathway choice. Only routes based on the shikimate pathway were thermodynamically favorable over a large concentration and pH range. The low pH capability of S. cerevisiae shifted the thermodynamic equilibrium of some pathways toward product formation. One identified infeasible-pattern revealed that the reversibility of the mitochondrial malate dehydrogenase contradicted the current state of knowledge, which imposes a major restriction on the metabolism of S. cerevisiae. Finally, the evaluation of industrially relevant constraints revealed that two shikimate pathway-based routes in E. coli were the most robust.

  2. Unraveling protein networks with power graph analysis.

    Directory of Open Access Journals (Sweden)

    Loïc Royer

    Full Text Available Networks play a crucial role in computational biology, yet their analysis and representation is still an open problem. Power Graph Analysis is a lossless transformation of biological networks into a compact, less redundant representation, exploiting the abundance of cliques and bicliques as elementary topological motifs. We demonstrate with five examples the advantages of Power Graph Analysis. Investigating protein-protein interaction networks, we show how the catalytic subunits of the casein kinase II complex are distinguishable from the regulatory subunits, how interaction profiles and sequence phylogeny of SH3 domains correlate, and how false positive interactions among high-throughput interactions are spotted. Additionally, we demonstrate the generality of Power Graph Analysis by applying it to two other types of networks. We show how power graphs induce a clustering of both transcription factors and target genes in bipartite transcription networks, and how the erosion of a phosphatase domain in type 22 non-receptor tyrosine phosphatases is detected. We apply Power Graph Analysis to high-throughput protein interaction networks and show that up to 85% (56% on average of the information is redundant. Experimental networks are more compressible than rewired ones of same degree distribution, indicating that experimental networks are rich in cliques and bicliques. Power Graphs are a novel representation of networks, which reduces network complexity by explicitly representing re-occurring network motifs. Power Graphs compress up to 85% of the edges in protein interaction networks and are applicable to all types of networks such as protein interactions, regulatory networks, or homology networks.

  3. The dichotomy in degree correlation of biological networks.

    Directory of Open Access Journals (Sweden)

    Dapeng Hao

    Full Text Available Most complex networks from different areas such as biology, sociology or technology, show a correlation on node degree where the possibility of a link between two nodes depends on their connectivity. It is widely believed that complex networks are either disassortative (links between hubs are systematically suppressed or assortative (links between hubs are enhanced. In this paper, we analyze a variety of biological networks and find that they generally show a dichotomous degree correlation. We find that many properties of biological networks can be explained by this dichotomy in degree correlation, including the neighborhood connectivity, the sickle-shaped clustering coefficient distribution and the modularity structure. This dichotomy distinguishes biological networks from real disassortative networks or assortative networks such as the Internet and social networks. We suggest that the modular structure of networks accounts for the dichotomy in degree correlation and vice versa, shedding light on the source of modularity in biological networks. We further show that a robust and well connected network necessitates the dichotomy of degree correlation, suggestive of an evolutionary motivation for its existence. Finally, we suggest that a dichotomous degree correlation favors a centrally connected modular network, by which the integrity of network and specificity of modules might be reconciled.

  4. 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:; 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:


    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.

  5. Inferring hidden causal relations between pathway members using reduced Google matrix of directed biological networks (United States)


    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

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

    Directory of Open Access Journals (Sweden)

    Martin Florian


    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

  7. Network Biology (

    Directory of Open Access Journals (Sweden)

    Full Text Available Network Biology ISSN 2220-8879 URL: RSS: E-mail: 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, 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

  8. Social network analysis

    NARCIS (Netherlands)

    de Nooy, W.; Crothers, C.


    Social network analysis (SNA) focuses on the structure of ties within a set of social actors, e.g., persons, groups, organizations, and nations, or the products of human activity or cognition such as web sites, semantic concepts, and so on. It is linked to structuralism in sociology stressing the

  9. Structural Analysis of Complex Networks

    CERN Document Server

    Dehmer, Matthias


    Filling a gap in literature, this self-contained book presents theoretical and application-oriented results that allow for a structural exploration of complex networks. The work focuses not only on classical graph-theoretic methods, but also demonstrates the usefulness of structural graph theory as a tool for solving interdisciplinary problems. Applications to biology, chemistry, linguistics, and data analysis are emphasized. The book is suitable for a broad, interdisciplinary readership of researchers, practitioners, and graduate students in discrete mathematics, statistics, computer science,

  10. Biology Question Generation from a Semantic Network (United States)

    Zhang, Lishan

    Science instructors need questions for use in exams, homework assignments, class discussions, reviews, and other instructional activities. Textbooks never have enough questions, so instructors must find them from other sources or generate their own questions. In order to supply instructors with biology questions, a semantic network approach was developed for generating open response biology questions. The generated questions were compared to professional authorized questions. To boost students' learning experience, adaptive selection was built on the generated questions. Bayesian Knowledge Tracing was used as embedded assessment of the student's current competence so that a suitable question could be selected based on the student's previous performance. A between-subjects experiment with 42 participants was performed, where half of the participants studied with adaptive selected questions and the rest studied with mal-adaptive order of questions. Both groups significantly improved their test scores, and the participants in adaptive group registered larger learning gains than participants in the control group. To explore the possibility of generating rich instructional feedback for machine-generated questions, a question-paragraph mapping task was identified. Given a set of questions and a list of paragraphs for a textbook, the goal of the task was to map the related paragraphs to each question. An algorithm was developed whose performance was comparable to human annotators. A multiple-choice question with high quality distractors (incorrect answers) can be pedagogically valuable as well as being much easier to grade than open-response questions. Thus, an algorithm was developed to generate good distractors for multiple-choice questions. The machine-generated multiple-choice questions were compared to human-generated questions in terms of three measures: question difficulty, question discrimination and distractor usefulness. By recruiting 200 participants from

  11. Managing biological networks by using text mining and computer-aided curation (United States)

    Yu, Seok Jong; Cho, Yongseong; Lee, Min-Ho; Lim, Jongtae; Yoo, Jaesoo


    In order to understand a biological mechanism in a cell, a researcher should collect a huge number of protein interactions with experimental data from experiments and the literature. Text mining systems that extract biological interactions from papers have been used to construct biological networks for a few decades. Even though the text mining of literature is necessary to construct a biological network, few systems with a text mining tool are available for biologists who want to construct their own biological networks. We have developed a biological network construction system called BioKnowledge Viewer that can generate a biological interaction network by using a text mining tool and biological taggers. It also Boolean simulation software to provide a biological modeling system to simulate the model that is made with the text mining tool. A user can download PubMed articles and construct a biological network by using the Multi-level Knowledge Emergence Model (KMEM), MetaMap, and A Biomedical Named Entity Recognizer (ABNER) as a text mining tool. To evaluate the system, we constructed an aging-related biological network that consist 9,415 nodes (genes) by using manual curation. With network analysis, we found that several genes, including JNK, AP-1, and BCL-2, were highly related in aging biological network. We provide a semi-automatic curation environment so that users can obtain a graph database for managing text mining results that are generated in the server system and can navigate the network with BioKnowledge Viewer, which is freely available at

  12. Network science of biological systems at different scales: A review (United States)

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


    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

  13. Network performance analysis

    CERN Document Server

    Bonald, Thomas


    The book presents some key mathematical tools for the performance analysis of communication networks and computer systems.Communication networks and computer systems have become extremely complex. The statistical resource sharing induced by the random behavior of users and the underlying protocols and algorithms may affect Quality of Service.This book introduces the main results of queuing theory that are useful for analyzing the performance of these systems. These mathematical tools are key to the development of robust dimensioning rules and engineering methods. A number of examples i

  14. Activating and inhibiting connections in biological network dynamics

    Directory of Open Access Journals (Sweden)

    Knight Rob


    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.

  15. Network systems security analysis (United States)

    Yilmaz, Ä.°smail


    Network Systems Security Analysis has utmost importance in today's world. Many companies, like banks which give priority to data management, test their own data security systems with "Penetration Tests" by time to time. In this context, companies must also test their own network/server systems and take precautions, as the data security draws attention. Based on this idea, the study cyber-attacks are researched throughoutly and Penetration Test technics are examined. With these information on, classification is made for the cyber-attacks and later network systems' security is tested systematically. After the testing period, all data is reported and filed for future reference. Consequently, it is found out that human beings are the weakest circle of the chain and simple mistakes may unintentionally cause huge problems. Thus, it is clear that some precautions must be taken to avoid such threats like updating the security software.

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

    CERN Document Server

    Koonin, Eugene V; Karev, Georgy P


    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...

  17. Mining biological networks from full-text articles. (United States)

    Czarnecki, Jan; Shepherd, Adrian J


    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.

  18. Analysis of computer networks

    CERN Document Server

    Gebali, Fayez


    This textbook presents the mathematical theory and techniques necessary for analyzing and modeling high-performance global networks, such as the Internet. The three main building blocks of high-performance networks are links, switching equipment connecting the links together, and software employed at the end nodes and intermediate switches. This book provides the basic techniques for modeling and analyzing these last two components. Topics covered include, but are not limited to: Markov chains and queuing analysis, traffic modeling, interconnection networks and switch architectures and buffering strategies.   ·         Provides techniques for modeling and analysis of network software and switching equipment; ·         Discusses design options used to build efficient switching equipment; ·         Includes many worked examples of the application of discrete-time Markov chains to communication systems; ·         Covers the mathematical theory and techniques necessary for ana...

  19. Stability from Structure : Metabolic Networks Are Unlike Other Biological Networks

    NARCIS (Netherlands)

    Van Nes, P.; Bellomo, D.; Reinders, M.J.T.; De Ridder, D.


    In recent work, attempts have been made to link the structure of biochemical networks to their complex dynamics. It was shown that structurally stable network motifs are enriched in such networks. In this work, we investigate to what extent these findings apply to metabolic networks. To this end, we

  20. VANLO - Interactive visual exploration of aligned biological networks

    Directory of Open Access Journals (Sweden)

    Linsen Lars


    Full Text Available Abstract Background Protein-protein interaction (PPI is fundamental to many biological processes. In the course of evolution, biological networks such as protein-protein interaction networks have developed. Biological networks of different species can be aligned by finding instances (e.g. proteins with the same common ancestor in the evolutionary process, so-called orthologs. For a better understanding of the evolution of biological networks, such aligned networks have to be explored. Visualization can play a key role in making the various relationships transparent. Results We present a novel visualization system for aligned biological networks in 3D space that naturally embeds existing 2D layouts. In addition to displaying the intra-network connectivities, we also provide insight into how the individual networks relate to each other by placing aligned entities on top of each other in separate layers. We optimize the layout of the entire alignment graph in a global fashion that takes into account inter- as well as intra-network relationships. The layout algorithm includes a step of merging aligned networks into one graph, laying out the graph with respect to application-specific requirements, splitting the merged graph again into individual networks, and displaying the network alignment in layers. In addition to representing the data in a static way, we also provide different interaction techniques to explore the data with respect to application-specific tasks. Conclusion Our system provides an intuitive global understanding of aligned PPI networks and it allows the investigation of key biological questions. We evaluate our system by applying it to real-world examples documenting how our system can be used to investigate the data with respect to these key questions. Our tool VANLO (Visualization of Aligned Networks with Layout Optimization can be accessed at

  1. PREFACE: Complex Networks: from Biology to Information Technology (United States)

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


    The field of complex networks is one of the most active areas in contemporary statistical physics. Ten years after seminal work initiated the modern study of networks, interest in the field is in fact still growing, as indicated by the ever increasing number of publications in network science. The reason for such a resounding success is most likely the simplicity and broad significance of the approach that, through graph theory, allows researchers to address a variety of different complex systems within a common framework. This special issue comprises a selection of contributions presented at the workshop 'Complex Networks: from Biology to Information Technology' held in July 2007 in Pula (Cagliari), Italy as a satellite of the general conference STATPHYS23. The contributions cover a wide range of problems that are currently among the most important questions in the area of complex networks and that are likely to stimulate future research. The issue is organised into four sections. The first two sections describe 'methods' to study the structure and the dynamics of complex networks, respectively. After this methodological part, the issue proceeds with a section on applications to biological systems. The issue closes with a section concentrating on applications to the study of social and technological networks. The first section, entitled Methods: The Structure, consists of six contributions focused on the characterisation and analysis of structural properties of complex networks: The paper Motif-based communities in complex networks by Arenas et al is a study of the occurrence of characteristic small subgraphs in complex networks. These subgraphs, known as motifs, are used to define general classes of nodes and their communities by extending the mathematical expression of the Newman-Girvan modularity. The same line of research, aimed at characterising network structure through the analysis of particular subgraphs, is explored by Bianconi and Gulbahce in Algorithm

  2. Communication on the structure of biological networks

    Indian Academy of Sciences (India)

    Networks are widely used to represent interaction pattern among the components in complex systems. Structures of real networks from different domains may vary quite significantly. As there is an interplay between network architecture and dynamics, structure plays an important role in communication and spreading of ...

  3. NFP: An R Package for Characterizing and Comparing of Annotated Biological Networks. (United States)

    Cao, Yang; Xu, Wenjian; Niu, Chao; Bo, Xiaochen; Li, Fei


    Large amounts of various biological networks exist for representing different types of interaction data, such as genetic, metabolic, gene regulatory, and protein-protein relationships. Recent approaches on biological network study are based on different mathematical concepts. It is necessary to construct a uniform framework to judge the functionality of biological networks. We recently introduced a knowledge-based computational framework that reliably characterized biological networks in system level. The method worked by making systematic comparisons to a set of well-studied "basic networks," measuring both the functional and topological similarities. A biological network could be characterized as a spectrum-like vector consisting of similarities to basic networks. Here, to facilitate the application, development, and adoption of this framework, we present an R package called NFP. This package extends our previous pipeline, offering a powerful set of functions for Network Fingerprint analysis. The software shows great potential in biological network study. The open source NFP R package is freely available under the GNU General Public License v2.0 at CRAN along with the vignette.

  4. NFP: An R Package for Characterizing and Comparing of Annotated Biological Networks

    Directory of Open Access Journals (Sweden)

    Yang Cao


    Full Text Available Large amounts of various biological networks exist for representing different types of interaction data, such as genetic, metabolic, gene regulatory, and protein-protein relationships. Recent approaches on biological network study are based on different mathematical concepts. It is necessary to construct a uniform framework to judge the functionality of biological networks. We recently introduced a knowledge-based computational framework that reliably characterized biological networks in system level. The method worked by making systematic comparisons to a set of well-studied “basic networks,” measuring both the functional and topological similarities. A biological network could be characterized as a spectrum-like vector consisting of similarities to basic networks. Here, to facilitate the application, development, and adoption of this framework, we present an R package called NFP. This package extends our previous pipeline, offering a powerful set of functions for Network Fingerprint analysis. The software shows great potential in biological network study. The open source NFP R package is freely available under the GNU General Public License v2.0 at CRAN along with the vignette.

  5. NDEx: A Community Resource for Sharing and Publishing of Biological Networks. (United States)

    Pillich, Rudolf T; Chen, Jing; Rynkov, Vladimir; Welker, David; Pratt, Dexter


    Networks are a powerful and flexible paradigm that facilitate communication and computation about interactions of any type, whether social, economic, or biological. NDEx, the Network Data Exchange, is an online commons to enable new modes of collaboration and publication using biological networks. NDEx creates an access point and interface to a broad range of networks, whether they express molecular interactions, curated relationships from literature, or the outputs of systematic analysis of big data. Research organizations can use NDEx as a distribution channel for networks they generate or curate. Developers of bioinformatic applications can store and query NDEx networks via a common programmatic interface. NDEx can also facilitate the integration of networks as data in electronic publications, thus making a step toward an ecosystem in which networks bearing data, hypotheses, and findings flow seamlessly between scientists.

  6. Stochastic flux analysis of chemical reaction networks. (United States)

    Kahramanoğulları, Ozan; Lynch, James F


    Chemical reaction networks provide an abstraction scheme for a broad range of models in biology and ecology. The two common means for simulating these networks are the deterministic and the stochastic approaches. The traditional deterministic approach, based on differential equations, enjoys a rich set of analysis techniques, including a treatment of reaction fluxes. However, the discrete stochastic simulations, which provide advantages in some cases, lack a quantitative treatment of network fluxes. We describe a method for flux analysis of chemical reaction networks, where flux is given by the flow of species between reactions in stochastic simulations of the network. Extending discrete event simulation algorithms, our method constructs several data structures, and thereby reveals a variety of statistics about resource creation and consumption during the simulation. We use these structures to quantify the causal interdependence and relative importance of the reactions at arbitrary time intervals with respect to the network fluxes. This allows us to construct reduced networks that have the same flux-behavior, and compare these networks, also with respect to their time series. We demonstrate our approach on an extended example based on a published ODE model of the same network, that is, Rho GTP-binding proteins, and on other models from biology and ecology. We provide a fully stochastic treatment of flux analysis. As in deterministic analysis, our method delivers the network behavior in terms of species transformations. Moreover, our stochastic analysis can be applied, not only at steady state, but at arbitrary time intervals, and used to identify the flow of specific species between specific reactions. Our cases study of Rho GTP-binding proteins reveals the role played by the cyclic reverse fluxes in tuning the behavior of this network.

  7. Systems biology of plant molecular networks: from networks to models

    NARCIS (Netherlands)

    Valentim, F.L.


    Developmental processes are controlled by regulatory networks (GRNs), which are tightly coordinated networks of transcription factors (TFs) that activate and repress gene expression within a spatial and temporal context. In Arabidopsis thaliana, the key components and network structures of the GRNs

  8. Fast network centrality analysis using GPUs

    Directory of Open Access Journals (Sweden)

    Shi Zhiao


    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

  9. A conceptual review on systems biology in health and diseases: from biological networks to modern therapeutics


    Somvanshi, Pramod Rajaram; Venkatesh, K. V.


    Human physiology is an ensemble of various biological processes spanning from intracellular molecular interactions to the whole body phenotypic response. Systems biology endures to decipher these multi-scale biological networks and bridge the link between genotype to phenotype. The structure and dynamic properties of these networks are responsible for controlling and deciding the phenotypic state of a cell. Several cells and various tissues coordinate together to generate an organ level respo...

  10. Integrating data from biological experiments into metabolic networks with the DBE information system. (United States)

    Borisjuk, Ljudmilla; Hajirezaei, Mohammad-Reza; Klukas, Christian; Rolletschek, Hardy; Schreiber, Falk


    Modern 'omics'-technologies result in huge amounts of data about life processes. For analysis and data mining purposes this data has to be considered in the context of the underlying biological networks. This work presents an approach for integrating data from biological experiments into metabolic networks by mapping the data onto network elements and visualising the data enriched networks automatically. This methodology is implemented in DBE, an information system that supports the analysis and visualisation of experimental data in the context of metabolic networks. It consists of five parts: (1) the DBE-Database for consistent data storage, (2) the Excel-Importer application for the data import, (3) the DBE-Website as the interface for the system, (4) the DBE-Pictures application for the up- and download of binary (e. g. image) files, and (5) DBE-Gravisto, a network analysis and graph visualisation system. The usability of this approach is demonstrated in two examples.

  11. Exploring community structure in biological networks with random graphs (United States)


    Background Community structure is ubiquitous in biological networks. There has been an increased interest in unraveling the community structure of biological systems as it may provide important insights into a system’s functional components and the impact of local structures on dynamics at a global scale. Choosing an appropriate community detection algorithm to identify the community structure in an empirical network can be difficult, however, as the many algorithms available are based on a variety of cost functions and are difficult to validate. Even when community structure is identified in an empirical system, disentangling the effect of community structure from other network properties such as clustering coefficient and assortativity can be a challenge. Results Here, we develop a generative model to produce undirected, simple, connected graphs with a specified degrees and pattern of communities, while maintaining a graph structure that is as random as possible. Additionally, we demonstrate two important applications of our model: (a) to generate networks that can be used to benchmark existing and new algorithms for detecting communities in biological networks; and (b) to generate null models to serve as random controls when investigating the impact of complex network features beyond the byproduct of degree and modularity in empirical biological networks. Conclusion Our model allows for the systematic study of the presence of community structure and its impact on network function and dynamics. This process is a crucial step in unraveling the functional consequences of the structural properties of biological systems and uncovering the mechanisms that drive these systems. PMID:24965130

  12. Systems biology: properties of reconstructed networks

    National Research Council Canada - National Science Library

    Palsson, Bernhard


    ... between the mathematical ideas and biological processes are made clear, the book reflects the irreversible trend of increasing mathematical content in biology education. Therefore to assist both teacher and student, Palsson provides problem sets, projects, and PowerPoint slides in an associated web site and keeps the presentation in the book concrete with illustrat...

  13. Epigenetics and Why Biological Networks are More Controllable than Expected (United States)

    Motter, Adilson


    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.

  14. The ultimate complex system: networks in molecular biology (United States)

    Schreiber, Andreas W.


    This contribution provides a brief survey of networks as they occur in molecular biology. It is intended as an introduction for a physics audience with no prior knowledge of molecular biology. References to key papers and reviews are included for the reader who wishes to explore this fascinating area further.

  15. A network biology approach to denitrification in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Seda Arat

    Full Text Available Pseudomonas aeruginosa is a metabolically flexible member of the Gammaproteobacteria. Under anaerobic conditions and the presence of nitrate, P. aeruginosa can perform (complete denitrification, a respiratory process of dissimilatory nitrate reduction to nitrogen gas via nitrite (NO2, nitric oxide (NO and nitrous oxide (N2O. This study focuses on understanding the influence of environmental conditions on bacterial denitrification performance, using a mathematical model of a metabolic network in P. aeruginosa. To our knowledge, this is the first mathematical model of denitrification for this bacterium. Analysis of the long-term behavior of the network under changing concentration levels of oxygen (O2, nitrate (NO3, and phosphate (PO4 suggests that PO4 concentration strongly affects denitrification performance. The model provides three predictions on denitrification activity of P. aeruginosa under various environmental conditions, and these predictions are either experimentally validated or supported by pertinent biological literature. One motivation for this study is to capture the effect of PO4 on a denitrification metabolic network of P. aeruginosa in order to shed light on mechanisms for greenhouse gas N2O accumulation during seasonal oxygen depletion in aquatic environments such as Lake Erie (Laurentian Great Lakes, USA. Simulating the microbial production of greenhouse gases in anaerobic aquatic systems such as Lake Erie allows a deeper understanding of the contributing environmental effects that will inform studies on, and remediation strategies for, other hypoxic sites worldwide.

  16. A network biology approach to denitrification in Pseudomonas aeruginosa. (United States)

    Arat, Seda; Bullerjahn, George S; Laubenbacher, Reinhard


    Pseudomonas aeruginosa is a metabolically flexible member of the Gammaproteobacteria. Under anaerobic conditions and the presence of nitrate, P. aeruginosa can perform (complete) denitrification, a respiratory process of dissimilatory nitrate reduction to nitrogen gas via nitrite (NO2), nitric oxide (NO) and nitrous oxide (N2O). This study focuses on understanding the influence of environmental conditions on bacterial denitrification performance, using a mathematical model of a metabolic network in P. aeruginosa. To our knowledge, this is the first mathematical model of denitrification for this bacterium. Analysis of the long-term behavior of the network under changing concentration levels of oxygen (O2), nitrate (NO3), and phosphate (PO4) suggests that PO4 concentration strongly affects denitrification performance. The model provides three predictions on denitrification activity of P. aeruginosa under various environmental conditions, and these predictions are either experimentally validated or supported by pertinent biological literature. One motivation for this study is to capture the effect of PO4 on a denitrification metabolic network of P. aeruginosa in order to shed light on mechanisms for greenhouse gas N2O accumulation during seasonal oxygen depletion in aquatic environments such as Lake Erie (Laurentian Great Lakes, USA). Simulating the microbial production of greenhouse gases in anaerobic aquatic systems such as Lake Erie allows a deeper understanding of the contributing environmental effects that will inform studies on, and remediation strategies for, other hypoxic sites worldwide.

  17. Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network. (United States)

    Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup


    Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. We herein introduce a framework for network modularization and Bayesian network analysis (FMB) to investigate organism's metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

  18. Two classes of bipartite networks: nested biological and social systems. (United States)

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


    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.

  19. Biological signals classification and analysis

    CERN Document Server

    Kiasaleh, Kamran


    This authored monograph presents key aspects of signal processing analysis in the biomedical arena. Unlike wireless communication systems, biological entities produce signals with underlying nonlinear, chaotic nature that elude classification using the standard signal processing techniques, which have been developed over the past several decades for dealing primarily with standard communication systems. This book separates what is random from that which appears to be random, and yet is truly deterministic with random appearance. At its core, this work gives the reader a perspective on biomedical signals and the means to classify and process such signals. In particular, a review of random processes along with means to assess the behavior of random signals is also provided. The book also includes a general discussion of biological signals in order to demonstrate the inefficacy of the well-known techniques to correctly extract meaningful information from such signals. Finally, a thorough discussion of recently ...

  20. 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.


    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.

  1. Human Dopamine Receptors Interaction Network (DRIN): a systems biology perspective on topology, stability and functionality of the network. (United States)

    Podder, Avijit; Jatana, Nidhi; Latha, N


    Dopamine receptors (DR) are one of the major neurotransmitter receptors present in human brain. Malfunctioning of these receptors is well established to trigger many neurological and psychiatric disorders. Taking into consideration that proteins function collectively in a network for most of the biological processes, the present study is aimed to depict the interactions between all dopamine receptors following a systems biology approach. To capture comprehensive interactions of candidate proteins associated with human dopamine receptors, we performed a protein-protein interaction network (PPIN) analysis of all five receptors and their protein partners by mapping them into human interactome and constructed a human Dopamine Receptors Interaction Network (DRIN). We explored the topology of dopamine receptors as molecular network, revealing their characteristics and the role of central network elements. More to the point, a sub-network analysis was done to determine major functional clusters in human DRIN that govern key neurological pathways. Besides, interacting proteins in a pathway were characterized and prioritized based on their affinity for utmost drug molecules. The vulnerability of different networks to the dysfunction of diverse combination of components was estimated under random and direct attack scenarios. To the best of our knowledge, the current study is unique to put all five dopamine receptors together in a common interaction network and to understand the functionality of interacting proteins collectively. Our study pinpointed distinctive topological and functional properties of human dopamine receptors that have helped in identifying potential therapeutic drug targets in the dopamine interaction network. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Network Analysis, Architecture, and Design

    CERN Document Server

    McCabe, James D


    Traditionally, networking has had little or no basis in analysis or architectural development, with designers relying on technologies they are most familiar with or being influenced by vendors or consultants. However, the landscape of networking has changed so that network services have now become one of the most important factors to the success of many third generation networks. It has become an important feature of the designer's job to define the problems that exist in his network, choose and analyze several optimization parameters during the analysis process, and then prioritize and evalua

  3. Polynomial-Time Algorithm for Controllability Test of a Class of Boolean Biological Networks

    Directory of Open Access Journals (Sweden)

    Koichi Kobayashi


    Full Text Available In recent years, Boolean-network-model-based approaches to dynamical analysis of complex biological networks such as gene regulatory networks have been extensively studied. One of the fundamental problems in control theory of such networks is the problem of determining whether a given substance quantity can be arbitrarily controlled by operating the other substance quantities, which we call the controllability problem. This paper proposes a polynomial-time algorithm for solving this problem. Although the algorithm is based on a sufficient condition for controllability, it is easily computable for a wider class of large-scale biological networks compared with the existing approaches. A key to this success in our approach is to give up computing Boolean operations in a rigorous way and to exploit an adjacency matrix of a directed graph induced by a Boolean network. By applying the proposed approach to a neurotransmitter signaling pathway, it is shown that it is effective.

  4. Information flow analysis of interactome networks.

    Directory of Open Access Journals (Sweden)

    Patrycja Vasilyev Missiuro


    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

  5. Network topology analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Kalb, Jeffrey L.; Lee, David S.


    Emerging high-bandwidth, low-latency network technology has made network-based architectures both feasible and potentially desirable for use in satellite payload architectures. The selection of network topology is a critical component when developing these multi-node or multi-point architectures. This study examines network topologies and their effect on overall network performance. Numerous topologies were reviewed against a number of performance, reliability, and cost metrics. This document identifies a handful of good network topologies for satellite applications and the metrics used to justify them as such. Since often multiple topologies will meet the requirements of the satellite payload architecture under development, the choice of network topology is not easy, and in the end the choice of topology is influenced by both the design characteristics and requirements of the overall system and the experience of the developer.

  6. Biological impacts and context of network theory

    Energy Technology Data Exchange (ETDEWEB)

    Almaas, E


    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.

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

    Directory of Open Access Journals (Sweden)

    Nicola J. Mulder


    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.

  8. Non-Hermitian localization in biological networks. (United States)

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


    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. Sensitivity analysis approaches applied to systems biology models. (United States)

    Zi, Z


    With the rising application of systems biology, sensitivity analysis methods have been widely applied to study the biological systems, including metabolic networks, signalling pathways and genetic circuits. Sensitivity analysis can provide valuable insights about how robust the biological responses are with respect to the changes of biological parameters and which model inputs are the key factors that affect the model outputs. In addition, sensitivity analysis is valuable for guiding experimental analysis, model reduction and parameter estimation. Local and global sensitivity analysis approaches are the two types of sensitivity analysis that are commonly applied in systems biology. Local sensitivity analysis is a classic method that studies the impact of small perturbations on the model outputs. On the other hand, global sensitivity analysis approaches have been applied to understand how the model outputs are affected by large variations of the model input parameters. In this review, the author introduces the basic concepts of sensitivity analysis approaches applied to systems biology models. Moreover, the author discusses the advantages and disadvantages of different sensitivity analysis methods, how to choose a proper sensitivity analysis approach, the available sensitivity analysis tools for systems biology models and the caveats in the interpretation of sensitivity analysis results.

  10. A flood-based information flow analysis and network minimization method for gene regulatory networks. (United States)

    Pavlogiannis, Andreas; Mozhayskiy, Vadim; Tagkopoulos, Ilias


    Biological networks tend to have high interconnectivity, complex topologies and multiple types of interactions. This renders difficult the identification of sub-networks that are involved in condition- specific responses. In addition, we generally lack scalable methods that can reveal the information flow in gene regulatory and biochemical pathways. Doing so will help us to identify key participants and paths under specific environmental and cellular context. This paper introduces the theory of network flooding, which aims to address the problem of network minimization and regulatory information flow in gene regulatory networks. Given a regulatory biological network, a set of source (input) nodes and optionally a set of sink (output) nodes, our task is to find (a) the minimal sub-network that encodes the regulatory program involving all input and output nodes and (b) the information flow from the source to the sink nodes of the network. Here, we describe a novel, scalable, network traversal algorithm and we assess its potential to achieve significant network size reduction in both synthetic and E. coli networks. Scalability and sensitivity analysis show that the proposed method scales well with the size of the network, and is robust to noise and missing data. The method of network flooding proves to be a useful, practical approach towards information flow analysis in gene regulatory networks. Further extension of the proposed theory has the potential to lead in a unifying framework for the simultaneous network minimization and information flow analysis across various "omics" levels.

  11. Parameterized algorithmics for finding connected motifs in biological networks. (United States)

    Betzler, Nadja; van Bevern, René; Fellows, Michael R; Komusiewicz, Christian; Niedermeier, Rolf


    We study the NP-hard LIST-COLORED GRAPH MOTIF problem which, given an undirected list-colored graph G = (V, E) and a multiset M of colors, asks for maximum-cardinality sets S ⊆ V and M' ⊆ M such that G[S] is connected and contains exactly (with respect to multiplicity) the colors in M'. LIST-COLORED GRAPH MOTIF has applications in the analysis of biological networks. We study LIST-COLORED GRAPH MOTIF with respect to three different parameterizations. For the parameters motif size |M| and solution size |S|, we present fixed-parameter algorithms, whereas for the parameter |V| - |M|, we show W[1]-hardness for general instances and achieve fixed-parameter tractability for a special case of LIST-COLORED GRAPH MOTIF. We implemented the fixed-parameter algorithms for parameters |M| and |S|, developed further speed-up heuristics for these algorithms, and applied them in the context of querying protein-interaction networks, demonstrating their usefulness for realistic instances. Furthermore, we show that extending the request for motif connectedness to stronger demands, such as biconnectedness or bridge-connectedness leads to W[1]-hard problems when the parameter is the motif size |M|.

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

    International Nuclear Information System (INIS)

    Clark, J.W.


    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.)

  13. Ising models of strongly coupled biological networks with multivariate interactions (United States)

    Merchan, Lina; Nemenman, Ilya


    Biological networks consist of a large number of variables that can be coupled by complex multivariate interactions. However, several neuroscience and cell biology experiments have reported that observed statistics of network states can be approximated surprisingly well by maximum entropy models that constrain correlations only within pairs of variables. We would like to verify if this reduction in complexity results from intricacies of biological organization, or if it is a more general attribute of these networks. We generate random networks with p-spin (p > 2) interactions, with N spins and M interaction terms. The probability distribution of the network states is then calculated and approximated with a maximum entropy model based on constraining pairwise spin correlations. Depending on the M/N ratio and the strength of the interaction terms, we observe a transition where the pairwise approximation is very good to a region where it fails. This resembles the sat-unsat transition in constraint satisfaction problems. We argue that the pairwise model works when the number of highly probable states is small. We argue that many biological systems must operate in a strongly constrained regime, and hence we expect the pairwise approximation to be accurate for a wide class of problems. This research has been partially supported by the James S McDonnell Foundation grant No.220020321.

  14. Making the right connections: Network biology and plant immune system dynamics

    Directory of Open Access Journals (Sweden)

    Maggie E. McCormack


    Full Text Available Network analysis has been a recent focus in biological sciences due to its ability to synthesize global visualizations of cellular processes and predict functions based on inferences from network properties. A protein–protein interaction network, or interactome, captures the emergent cellular states from gene regulation and environmental conditions. Given that proteins are involved in extensive local and systemic molecular interactions such as signaling and metabolism, understanding protein functions and interactions are essential for a systems view of biology. However, in plant sciences these network-based approaches to data integration have been few and far between due to limited data, especially protein–protein interaction data. In this review, we cover network construction from experimental data, network analysis based on topological properties, and finally we discuss advances in networks in plants and other organisms in a comparative approach. We focus on applications of network biology to discover the dynamics of host–pathogen interactions as these have potential agricultural uses in improving disease resistance in commercial crops.

  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.


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

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


    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.

  17. 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


    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.

  18. Decentralized control of ecological and biological networks through Evolutionary Network Control

    Directory of Open Access Journals (Sweden)

    Alessandro Ferrarini


    Full Text Available Evolutionary Network Control (ENC has been recently introduced to allow the control of any kind of ecological and biological networks, with an arbitrary number of nodes and links, acting from inside and/or outside. To date, ENC has been applied using a centralized approach where an arbitrary number of network nodes and links could be tamed. This approach has shown to be effective in the control of ecological and biological networks. However a decentralized control, where only one node and the correspondent input/output links are controlled, could be more economic from a computational viewpoint, in particular when the network is very large (i.e. big data. In this view, ENC is upgraded here to realize the decentralized control of ecological and biological nets.

  19. Uncovering Biological Network Function via Graphlet Degree Signatures

    Directory of Open Access Journals (Sweden)

    Nataša Pržulj


    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.

  20. The effect of network biology on drug toxicology

    DEFF Research Database (Denmark)

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


    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...... biology has the opportunity to contribute to a better understanding of a drug's safety profile. The authors believe that considering a drug action and protein's function in a global physiological environment may benefit our understanding of the impact some chemicals have on human health and toxicity...

  1. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens


    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...

  2. The impact of network biology in pharmacology and toxicology

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Taboureau, Olivier


    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 physiologic...

  3. Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions (United States)

    Semenov, Sergey N.; Kraft, Lewis J.; Ainla, Alar; Zhao, Mengxia; Baghbanzadeh, Mostafa; Campbell, Victoria E.; Kang, Kyungtae; Fox, Jerome M.; Whitesides, George M.


    Networks of organic chemical reactions are important in life and probably played a central part in its origin. Network dynamics regulate cell division, circadian rhythms, nerve impulses and chemotaxis, and guide the development of organisms. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics such as spontaneous pattern formation, bistability and periodic oscillations, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate-thioester exchange, thiolate-disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes and DNA) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov-Zhabotinskii-type reactions), the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving

  4. Robustness leads close to the edge of chaos in coupled map networks: toward the understanding of biological networks (United States)

    Saito, Nen; Kikuchi, Macoto


    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.

  5. [Application of network biology on study of traditional Chinese medicine]. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Jose A. Santiago


    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.

  7. Fast grid layout algorithm for biological networks with sweep calculation. (United States)

    Kojima, Kaname; Nagasaki, Masao; Miyano, Satoru


    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. Supplementary data are available at Bioinformatics online.

  8. Computational Social Network Analysis

    CERN Document Server

    Hassanien, Aboul-Ella


    Presents insight into the social behaviour of animals (including the study of animal tracks and learning by members of the same species). This book provides web-based evidence of social interaction, perceptual learning, information granulation and the behaviour of humans and affinities between web-based social networks

  9. Network analysis applications in hydrology (United States)

    Price, Katie


    Applied network theory has seen pronounced expansion in recent years, in fields such as epidemiology, computer science, and sociology. Concurrent development of analytical methods and frameworks has increased possibilities and tools available to researchers seeking to apply network theory to a variety of problems. While water and nutrient fluxes through stream systems clearly demonstrate a directional network structure, the hydrological applications of network theory remain under­explored. This presentation covers a review of network applications in hydrology, followed by an overview of promising network analytical tools that potentially offer new insights into conceptual modeling of hydrologic systems, identifying behavioral transition zones in stream networks and thresholds of dynamical system response. Network applications were tested along an urbanization gradient in Atlanta, Georgia, USA. Peachtree Creek and Proctor Creek. Peachtree Creek contains a nest of five long­term USGS streamflow and water quality gages, allowing network application of long­term flow statistics. The watershed spans a range of suburban and heavily urbanized conditions. Summary flow statistics and water quality metrics were analyzed using a suite of network analysis techniques, to test the conceptual modeling and predictive potential of the methodologies. Storm events and low flow dynamics during Summer 2016 were analyzed using multiple network approaches, with an emphasis on tomogravity methods. Results indicate that network theory approaches offer novel perspectives for understanding long­ term and event­based hydrological data. Key future directions for network applications include 1) optimizing data collection, 2) identifying "hotspots" of contaminant and overland flow influx to stream systems, 3) defining process domains, and 4) analyzing dynamic connectivity of various system components, including groundwater­surface water interactions.

  10. Topological analysis of telecommunications networks

    Directory of Open Access Journals (Sweden)

    Milojko V. Jevtović


    Full Text Available A topological analysis of the structure of telecommunications networks is a very interesting topic in the network research, but also a key issue in their design and planning. Satisfying multiple criteria in terms of locations of switching nodes as well as their connectivity with respect to the requests for capacity, transmission speed, reliability, availability and cost are the main research objectives. There are three ways of presenting the topology of telecommunications networks: table, matrix or graph method. The table method is suitable for a network of a relatively small number of nodes in relation to the number of links. The matrix method involves the formation of a connection matrix in which its columns present source traffic nodes and its rows are the switching systems that belong to the destination. The method of the topology graph means that the network nodes are connected via directional or unidirectional links. We can thus easily analyze the structural parameters of telecommunications networks. This paper presents the mathematical analysis of the star-, ring-, fully connected loop- and grid (matrix-shaped topology as well as the topology based on the shortest path tree. For each of these topologies, the expressions for determining the number of branches, the middle level of reliability, the medium length and the average length of the link are given in tables. For the fully connected loop network with five nodes the values of all topological parameters are calculated. Based on the topological parameters, the relationships that represent integral and distributed indicators of reliability are given in this work as well as the values of the particular network. The main objectives of the topology optimization of telecommunications networks are: achieving the minimum complexity, maximum capacity, the shortest path message transfer, the maximum speed of communication and maximum economy. The performance of telecommunications networks is

  11. Adaptation, Growth, and Resilience in Biological Distribution Networks (United States)

    Ronellenfitsch, Henrik; Katifori, Eleni

    Highly optimized complex transport networks serve crucial functions in many man-made and natural systems such as power grids and plant or animal vasculature. Often, the relevant optimization functional is nonconvex and characterized by many local extrema. In general, finding the global, or nearly global optimum is difficult. In biological systems, it is believed that such an optimal state is slowly achieved through natural selection. However, general coarse grained models for flow networks with local positive feedback rules for the vessel conductivity typically get trapped in low efficiency, local minima. We show how the growth of the underlying tissue, coupled to the dynamical equations for network development, can drive the system to a dramatically improved optimal state. This general model provides a surprisingly simple explanation for the appearance of highly optimized transport networks in biology such as plant and animal vasculature. In addition, we show how the incorporation of spatially collective fluctuating sources yields a minimal model of realistic reticulation in distribution networks and thus resilience against damage.

  12. Analysis of neural networks

    CERN Document Server

    Heiden, Uwe


    The purpose of this work is a unified and general treatment of activity in neural networks from a mathematical pOint of view. Possible applications of the theory presented are indica­ ted throughout the text. However, they are not explored in de­ tail for two reasons : first, the universal character of n- ral activity in nearly all animals requires some type of a general approach~ secondly, the mathematical perspicuity would suffer if too many experimental details and empirical peculiarities were interspersed among the mathematical investigation. A guide to many applications is supplied by the references concerning a variety of specific issues. Of course the theory does not aim at covering all individual problems. Moreover there are other approaches to neural network theory (see e.g. Poggio-Torre, 1978) based on the different lev­ els at which the nervous system may be viewed. The theory is a deterministic one reflecting the average be­ havior of neurons or neuron pools. In this respect the essay is writt...

  13. Network enrichment analysis: extension of gene-set enrichment analysis to gene networks

    Directory of Open Access Journals (Sweden)

    Alexeyenko Andrey


    Full Text Available Abstract Background Gene-set enrichment analyses (GEA or GSEA are commonly used for biological characterization of an experimental gene-set. This is done by finding known functional categories, such as pathways or Gene Ontology terms, that are over-represented in the experimental set; the assessment is based on an overlap statistic. Rich biological information in terms of gene interaction network is now widely available, but this topological information is not used by GEA, so there is a need for methods that exploit this type of information in high-throughput data analysis. Results We developed a method of network enrichment analysis (NEA that extends the overlap statistic in GEA to network links between genes in the experimental set and those in the functional categories. For the crucial step in statistical inference, we developed a fast network randomization algorithm in order to obtain the distribution of any network statistic under the null hypothesis of no association between an experimental gene-set and a functional category. We illustrate the NEA method using gene and protein expression data from a lung cancer study. Conclusions The results indicate that the NEA method is more powerful than the traditional GEA, primarily because the relationships between gene sets were more strongly captured by network connectivity rather than by simple overlaps.

  14. Network-based analysis of proteomic profiles

    KAUST Repository

    Wong, Limsoon


    Mass spectrometry (MS)-based proteomics is a widely used and powerful tool for profiling systems-wide protein expression changes. It can be applied for various purposes, e.g. biomarker discovery in diseases and study of drug responses. Although RNA-based high-throughput methods have been useful in providing glimpses into the underlying molecular processes, the evidences they provide are indirect. Furthermore, RNA and corresponding protein levels have been known to have poor correlation. On the other hand, MS-based proteomics tend to have consistency issues (poor reproducibility and inter-sample agreement) and coverage issues (inability to detect the entire proteome) that need to be urgently addressed. In this talk, I will discuss how these issues can be addressed by proteomic profile analysis techniques that use biological networks (especially protein complexes) as the biological context. In particular, I will describe several techniques that we have been developing for network-based analysis of proteomics profile. And I will present evidence that these techniques are useful in identifying proteomics-profile analysis results that are more consistent, more reproducible, and more biologically coherent, and that these techniques allow expansion of the detected proteome to uncover and/or discover novel proteins.

  15. Differential network analysis in human cancer research. (United States)

    Gill, Ryan; Datta, Somnath; Datta, Susmita


    A complex disease like cancer is hardly caused by one gene or one protein singly. It is usually caused by the perturbation of the network formed by several genes or proteins. In the last decade several research teams have attempted to construct interaction maps of genes and proteins either experimentally or reverse engineer interaction maps using computational techniques. These networks were usually created under a certain condition such as an environmental condition, a particular disease, or a specific tissue type. Lately, however, there has been greater emphasis on finding the differential structure of the existing network topology under a novel condition or disease status to elucidate the perturbation in a biological system. In this review/tutorial article we briefly mention some of the research done in this area; we mainly illustrate the computational/statistical methods developed by our team in recent years for differential network analysis using publicly available gene expression data collected from a well known cancer study. This data includes a group of patients with acute lymphoblastic leukemia and a group with acute myeloid leukemia. In particular, we describe the statistical tests to detect the change in the network topology based on connectivity scores which measure the association or interaction between pairs of genes. The tests under various scores are applied to this data set to perform a differential network analysis on gene expression for human leukemia. We believe that, in the future, differential network analysis will be a standard way to view the changes in gene expression and protein expression data globally and these types of tests could be useful in analyzing the complex differential signatures.

  16. Surface analysis and techniques in biology

    CERN Document Server

    Smentkowski, Vincent S


    This book highlights state-of-the-art surface analytical instrumentation, advanced data analysis tools, and the use of complimentary surface analytical instrumentation to perform a complete analysis of biological systems.

  17. Antenna analysis using neural networks (United States)

    Smith, William T.


    Conventional computing schemes have long been used to analyze problems in electromagnetics (EM). The vast majority of EM applications require computationally intensive algorithms involving numerical integration and solutions to large systems of equations. The feasibility of using neural network computing algorithms for antenna analysis is investigated. The ultimate goal is to use a trained neural network algorithm to reduce the computational demands of existing reflector surface error compensation techniques. Neural networks are computational algorithms based on neurobiological systems. Neural nets consist of massively parallel interconnected nonlinear computational elements. They are often employed in pattern recognition and image processing problems. Recently, neural network analysis has been applied in the electromagnetics area for the design of frequency selective surfaces and beam forming networks. The backpropagation training algorithm was employed to simulate classical antenna array synthesis techniques. The Woodward-Lawson (W-L) and Dolph-Chebyshev (D-C) array pattern synthesis techniques were used to train the neural network. The inputs to the network were samples of the desired synthesis pattern. The outputs are the array element excitations required to synthesize the desired pattern. Once trained, the network is used to simulate the W-L or D-C techniques. Various sector patterns and cosecant-type patterns (27 total) generated using W-L synthesis were used to train the network. Desired pattern samples were then fed to the neural network. The outputs of the network were the simulated W-L excitations. A 20 element linear array was used. There were 41 input pattern samples with 40 output excitations (20 real parts, 20 imaginary). A comparison between the simulated and actual W-L techniques is shown for a triangular-shaped pattern. Dolph-Chebyshev is a different class of synthesis technique in that D-C is used for side lobe control as opposed to pattern

  18. Impact of heuristics in clustering large biological networks. (United States)

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


    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.

  19. Prediction of biological motion perception performance from intrinsic brain network regional efficiency

    Directory of Open Access Journals (Sweden)

    Zengjian Wang


    Full Text Available Biological motion perception (BMP is a vivid perception of the moving form of a human figure from a few light points on the joints of the body. BMP is commonplace and important, but there is great inter-individual variability in this ability. This study used multiple regression model analysis to explore the association between the BMP performance and intrinsic brain activity, in order to investigate the neural substrates underlying inter-individual variability of BMP performance. The resting-state functional magnetic resonance imaging (rs-fMRI and BMP performance data were collected from 24 healthy participants. For each participant, the intrinsic brain network was constructed, and a graph-based network efficiency metric was measured. Then, a multiple linear regression model was used to explore the association between network regional efficiency and BMP performance. We found that the local and global network efficiency of many regions was significantly correlated with the BMP performance. Further analysis showed that the local efficiency rather than global efficiency could be used to explain most of the BMP inter-individual variability, and the regions involved were predominately located at the Default Mode Network (DMN. Additionally, the discrimination analysis showed that the local efficiency over regions including thalamus could be used to classify BMP performance across participants. Notably, the association pattern between the network nodal efficiency and the BMP was different from the association pattern that of the static directional/gender information perception. Overall, these findings showed that intrinsic brain network efficiency may be considered as a neural factor that explains BMP inter-individual variability. Keywords: Biological motion; Resting-state network; Network efficiency; Multiple linear regression model; Brain-behavior analysis

  20. Analysis and enumeration algorithms for biological graphs

    CERN Document Server

    Marino, Andrea


    In this work we plan to revise the main techniques for enumeration algorithms and to show four examples of enumeration algorithms that can be applied to efficiently deal with some biological problems modelled by using biological networks: enumerating central and peripheral nodes of a network, enumerating stories, enumerating paths or cycles, and enumerating bubbles. Notice that the corresponding computational problems we define are of more general interest and our results hold in the case of arbitrary graphs. Enumerating all the most and less central vertices in a network according to their eccentricity is an example of an enumeration problem whose solutions are polynomial and can be listed in polynomial time, very often in linear or almost linear time in practice. Enumerating stories, i.e. all maximal directed acyclic subgraphs of a graph G whose sources and targets belong to a predefined subset of the vertices, is on the other hand an example of an enumeration problem with an exponential number of solutions...

  1. Tofacitinib versus Biologic Treatments in Moderate-to-Severe Rheumatoid Arthritis Patients Who Have Had an Inadequate Response to Nonbiologic DMARDs: Systematic Literature Review and Network Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Evelien Bergrath


    Full Text Available Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA, as monotherapy and combined with disease-modifying antirheumatic drugs (DMARDs versus biological DMARDs (bDMARDs and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA patients by means of a systematic literature review (SLR and network meta-analysis (NMA. Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs published between 1990 and March 2015. Efficacy data based on American College of Rheumatology (ACR response criteria, improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI at 6 months, and discontinuation rates due to adverse events were analyzed by means of Bayesian NMAs. Results. 45 RCTs were identified, the majority of which demonstrated a low risk of bias. Tofacitinib 5 mg twice daily (BID and 10 mg BID monotherapy exhibited comparable efficacy and discontinuation rates due to adverse events versus other monotherapies. Tofacitinib 5 mg BID and 10 mg BID + DMARDs or methotrexate (MTX were mostly comparable to other combination therapies in terms of efficacy and discontinuation due to adverse events. Conclusion. In most cases, tofacitinib had similar efficacy and discontinuation rates due to adverse events compared to biologic DMARDs.

  2. NET-2 Network Analysis Program

    International Nuclear Information System (INIS)

    Malmberg, A.F.


    The NET-2 Network Analysis Program is a general purpose digital computer program which solves the nonlinear time domain response and the linearized small signal frequency domain response of an arbitrary network of interconnected components. NET-2 is capable of handling a variety of components and has been applied to problems in several engineering fields, including electronic circuit design and analysis, missile flight simulation, control systems, heat flow, fluid flow, mechanical systems, structural dynamics, digital logic, communications network design, solid state device physics, fluidic systems, and nuclear vulnerability due to blast, thermal, gamma radiation, neutron damage, and EMP effects. Network components may be selected from a repertoire of built-in models or they may be constructed by the user through appropriate combinations of mathematical, empirical, and topological functions. Higher-level components may be defined by subnetworks composed of any combination of user-defined components and built-in models. The program provides a modeling capability to represent and intermix system components on many levels, e.g., from hole and electron spatial charge distributions in solid state devices through discrete and integrated electronic components to functional system blocks. NET-2 is capable of simultaneous computation in both the time and frequency domain, and has statistical and optimization capability. Network topology may be controlled as a function of the network solution. (U.S.)

  3. Predicting genetic interactions with random walks on biological networks

    Directory of Open Access Journals (Sweden)

    Singh Ambuj K


    Full Text Available Abstract Background Several studies have demonstrated that synthetic lethal genetic interactions between gene mutations provide an indication of functional redundancy between molecular complexes and pathways. These observations help explain the finding that organisms are able to tolerate single gene deletions for a large majority of genes. For example, system-wide gene knockout/knockdown studies in S. cerevisiae and C. elegans revealed non-viable phenotypes for a mere 18% and 10% of the genome, respectively. It has been postulated that the low percentage of essential genes reflects the extensive amount of genetic buffering that occurs within genomes. Consistent with this hypothesis, systematic double-knockout screens in S. cerevisiae and C. elegans show that, on average, 0.5% of tested gene pairs are synthetic sick or synthetic lethal. While knowledge of synthetic lethal interactions provides valuable insight into molecular functionality, testing all combinations of gene pairs represents a daunting task for molecular biologists, as the combinatorial nature of these relationships imposes a large experimental burden. Still, the task of mapping pairwise interactions between genes is essential to discovering functional relationships between molecular complexes and pathways, as they form the basis of genetic robustness. Towards the goal of alleviating the experimental workload, computational techniques that accurately predict genetic interactions can potentially aid in targeting the most likely candidate interactions. Building on previous studies that analyzed properties of network topology to predict genetic interactions, we apply random walks on biological networks to accurately predict pairwise genetic interactions. Furthermore, we incorporate all published non-interactions into our algorithm for measuring the topological relatedness between two genes. We apply our method to S. cerevisiae and C. elegans datasets and, using a decision tree

  4. From biological neural networks to thinking machines: Transitioning biological organizational principles to computer technology (United States)

    Ross, Muriel D.


    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.

  5. The Default Mode Network Differentiates Biological From Non-Biological Motion. (United States)

    Dayan, Eran; Sella, Irit; Mukovskiy, Albert; Douek, Yehonatan; Giese, Martin A; Malach, Rafael; Flash, Tamar


    The default mode network (DMN) has been implicated in an array of social-cognitive functions, including self-referential processing, theory of mind, and mentalizing. Yet, the properties of the external stimuli that elicit DMN activity in relation to these domains remain unknown. Previous studies suggested that motion kinematics is utilized by the brain for social-cognitive processing. Here, we used functional MRI to examine whether the DMN is sensitive to parametric manipulations of observed motion kinematics. Preferential responses within core DMN structures differentiating non-biological from biological kinematics were observed for the motion of a realistically looking, human-like avatar, but not for an abstract object devoid of human form. Differences in connectivity patterns during the observation of biological versus non-biological kinematics were additionally observed. Finally, the results additionally suggest that the DMN is coupled more strongly with key nodes in the action observation network, namely the STS and the SMA, when the observed motion depicts human rather than abstract form. These findings are the first to implicate the DMN in the perception of biological motion. They may reflect the type of information used by the DMN in social-cognitive processing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

  6. Biological instability in a chlorinated drinking water distribution network. (United States)

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


    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.

  7. NEAT : an efficient network enrichment analysis test

    NARCIS (Netherlands)

    Signorelli, Mirko; Vinciotti, Veronica; Wit, Ernst C


    BACKGROUND: Network enrichment analysis is a powerful method, which allows to integrate gene enrichment analysis with the information on relationships between genes that is provided by gene networks. Existing tests for network enrichment analysis deal only with undirected networks, they can be

  8. Nonlinear analysis of biological sequences

    Energy Technology Data Exchange (ETDEWEB)

    Torney, D.C.; Bruno, W.; Detours, V. [and others


    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The main objectives of this project involved deriving new capabilities for analyzing biological sequences. The authors focused on tabulating the statistical properties exhibited by Human coding DNA sequences and on techniques of inferring the phylogenetic relationships among protein sequences related by descent.

  9. Boolean Networks in Inference and Dynamic Modeling of Biological Systems at the Molecular and Physiological Level (United States)

    Thakar, Juilee; Albert, Réka

    The following sections are included: * Introduction * Boolean Network Concepts and History * Extensions of the Classical Boolean Framework * Boolean Inference Methods and Examples in Biology * Dynamic Boolean Models: Examples in Plant Biology, Developmental Biology and Immunology * Conclusions * References

  10. Social Networks Analysis: Classification, Evaluation, and Methodologies (United States)


    and time performance. We also focus on large-scale network size and dynamic changes in networks and research new capabilities in performing social networks analysis utilizing parallel and distributed processing.

  11. Statistical network analysis for analyzing policy networks

    DEFF Research Database (Denmark)

    Robins, Garry; Lewis, Jenny; Wang, Peng


    and policy network methodology is the development of statistical modeling approaches that can accommodate such dependent data. In this article, we review three network statistical methods commonly used in the current literature: quadratic assignment procedures, exponential random graph models (ERGMs...... has much to offer in analyzing the policy process....

  12. Enabling dynamic network analysis through visualization in TVNViewer

    Directory of Open Access Journals (Sweden)

    Curtis Ross E


    Full Text Available Abstract Background Many biological processes are context-dependent or temporally specific. As a result, relationships between molecular constituents evolve across time and environments. While cutting-edge machine learning techniques can recover these networks, exploring and interpreting the rewiring behavior is challenging. Information visualization shines in this type of exploratory analysis, motivating the development ofTVNViewer (, a visualization tool for dynamic network analysis. Results In this paper, we demonstrate visualization techniques for dynamic network analysis by using TVNViewer to analyze yeast cell cycle and breast cancer progression datasets. Conclusions TVNViewer is a powerful new visualization tool for the analysis of biological networks that change across time or space.

  13. Enabling dynamic network analysis through visualization in TVNViewer (United States)


    Background Many biological processes are context-dependent or temporally specific. As a result, relationships between molecular constituents evolve across time and environments. While cutting-edge machine learning techniques can recover these networks, exploring and interpreting the rewiring behavior is challenging. Information visualization shines in this type of exploratory analysis, motivating the development ofTVNViewer (, a visualization tool for dynamic network analysis. Results In this paper, we demonstrate visualization techniques for dynamic network analysis by using TVNViewer to analyze yeast cell cycle and breast cancer progression datasets. Conclusions TVNViewer is a powerful new visualization tool for the analysis of biological networks that change across time or space. PMID:22897913

  14. Statistical analysis of network data with R

    CERN Document Server

    Kolaczyk, Eric D


    Networks have permeated everyday life through everyday realities like the Internet, social networks, and viral marketing. As such, network analysis is an important growth area in the quantitative sciences, with roots in social network analysis going back to the 1930s and graph theory going back centuries. Measurement and analysis are integral components of network research. As a result, statistical methods play a critical role in network analysis. This book is the first of its kind in network research. It can be used as a stand-alone resource in which multiple R packages are used to illustrate how to conduct a wide range of network analyses, from basic manipulation and visualization, to summary and characterization, to modeling of network data. The central package is igraph, which provides extensive capabilities for studying network graphs in R. This text builds on Eric D. Kolaczyk’s book Statistical Analysis of Network Data (Springer, 2009).

  15. 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.


    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.

  16. 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.

  17. Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA). (United States)

    Singh, Jasvinder A; Hossain, Alomgir; Tanjong Ghogomu, Elizabeth; Mudano, Amy S; Tugwell, Peter; Wells, George A


    We performed a systematic review, a standard meta-analysis and network meta-analysis (NMA), which updates the 2009 Cochrane Overview, 'Biologics for rheumatoid arthritis (RA)'. This review is focused on biologic monotherapy in people with RA in whom treatment with traditional disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) had failed (MTX/other DMARD-experienced). To assess the benefits and harms of biologic monotherapy (includes anti-tumor necrosis factor (TNF) (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) or non-TNF (abatacept, anakinra, rituximab, tocilizumab)) or tofacitinib monotherapy (oral small molecule) versus comparator (placebo or MTX/other DMARDs) in adults with RA who were MTX/other DMARD-experienced. We searched for randomized controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2015, Issue 6, June), MEDLINE (via OVID 1946 to June 2015), and Embase (via OVID 1947 to June 2015). Article selection, data extraction and risk of bias and GRADE assessments were done in duplicate. We calculated direct estimates with 95% confidence intervals (CI) using standard meta-analysis. We used a Bayesian mixed treatment comparisons (MTC) approach for NMA estimates with 95% credible intervals (CrI). We converted odds ratios (OR) to risk ratios (RR) for ease of understanding. We calculated absolute measures as risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB). This update includes 40 new RCTs for a total of 46 RCTs, of which 41 studies with 14,049 participants provided data. The comparator was placebo in 16 RCTs (4,532 patients), MTX or other DMARD in 13 RCTs (5,602 patients), and another biologic in 12 RCTs (3,915 patients). Monotherapy versus placeboBased on moderate-quality direct evidence, biologic monotherapy (without concurrent MTX/other DMARDs) was associated with a clinically meaningful and statistically significant

  18. Biologically-inspired Learning in Pulsed Neural Networks

    DEFF Research Database (Denmark)

    Lehmann, Torsten; Woodburn, Robin


    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...... that useful conclusions as to the future of on-chip learning can be drawn from this work....

  19. Methods of information theory and algorithmic complexity for network biology. (United States)

    Zenil, Hector; Kiani, Narsis A; Tegnér, Jesper


    We survey and introduce concepts and tools located at the intersection of information theory and network biology. We show that Shannon's information entropy, compressibility and algorithmic complexity quantify different local and global aspects of synthetic and biological data. We show examples such as the emergence of giant components in Erdös-Rényi random graphs, and the recovery of topological properties from numerical kinetic properties simulating gene expression data. We provide exact theoretical calculations, numerical approximations and error estimations of entropy, algorithmic probability and Kolmogorov complexity for different types of graphs, characterizing their variant and invariant properties. We introduce formal definitions of complexity for both labeled and unlabeled graphs and prove that the Kolmogorov complexity of a labeled graph is a good approximation of its unlabeled Kolmogorov complexity and thus a robust definition of graph complexity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. GraphAlignment: Bayesian pairwise alignment of biological networks

    Directory of Open Access Journals (Sweden)

    Kolář Michal


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

    De Domenico, Manlio


    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.

  2. Spectral Analysis of Rich Network Topology in Social Networks (United States)

    Wu, Leting


    Social networks have received much attention these days. Researchers have developed different methods to study the structure and characteristics of the network topology. Our focus is on spectral analysis of the adjacency matrix of the underlying network. Recent work showed good properties in the adjacency spectral space but there are few…

  3. Analysis of Semantic Networks using Complex Networks Concepts

    DEFF Research Database (Denmark)

    Ortiz-Arroyo, Daniel


    In this paper we perform a preliminary analysis of semantic networks to determine the most important terms that could be used to optimize a summarization task. In our experiments, we measure how the properties of a semantic network change, when the terms in the network are removed. Our preliminary...

  4. Complex Network Analysis of Guangzhou Metro


    Yasir Tariq Mohmand; Fahad Mehmood; Fahd Amjad; Nedim Makarevic


    The structure and properties of public transportation networks can provide suggestions for urban planning and public policies. This study contributes a complex network analysis of the Guangzhou metro. The metro network has 236 kilometers of track and is the 6th busiest metro system of the world. In this paper topological properties of the network are explored. We observed that the network displays small world properties and is assortative in nature. The network possesses a high average degree...

  5. COalitions in COOperation Networks (COCOON): Social Network Analysis and Game Theory to Enhance Cooperation Networks

    NARCIS (Netherlands)

    Sie, Rory


    Sie, R. L. L. (2012). COalitions in COOperation Networks (COCOON): Social Network Analysis and Game Theory to Enhance Cooperation Networks (Unpublished doctoral dissertation). September, 28, 2012, Open Universiteit in the Netherlands (CELSTEC), Heerlen, The Netherlands.

  6. Analysis of single biological cells

    International Nuclear Information System (INIS)

    Watt, Frank


    The extraction of elemental information from single cultured cells using nuclear microscopy is an area of great potential because it can provide both quantitative information on the uptake of elements by the cell, and also its elemental response to a wide variety of external stimuli. A recent technique based on nuclear physics technology enables the analysis of single cells down to the parts per million level to be achieved

  7. The reconstruction and analysis of tissue specific human metabolic networks. (United States)

    Hao, Tong; Ma, Hong-Wu; Zhao, Xue-Ming; Goryanin, Igor


    Human tissues have distinct biological functions. Many proteins/enzymes are known to be expressed only in specific tissues and therefore the metabolic networks in various tissues are different. Though high quality global human metabolic networks and metabolic networks for certain tissues such as liver have already been studied, a systematic study of tissue specific metabolic networks for all main tissues is still missing. In this work, we reconstruct the tissue specific metabolic networks for 15 main tissues in human based on the previously reconstructed Edinburgh Human Metabolic Network (EHMN). The tissue information is firstly obtained for enzymes from Human Protein Reference Database (HPRD) and UniprotKB databases and transfers to reactions through the enzyme-reaction relationships in EHMN. As our knowledge of tissue distribution of proteins is still very limited, we replenish the tissue information of the metabolic network based on network connectivity analysis and thorough examination of the literature. Finally, about 80% of proteins and reactions in EHMN are determined to be in at least one of the 15 tissues. To validate the quality of the tissue specific network, the brain specific metabolic network is taken as an example for functional module analysis and the results reveal that the function of the brain metabolic network is closely related with its function as the centre of the human nervous system. The tissue specific human metabolic networks are available at .

  8. Quantum Processes and Dynamic Networks in Physical and Biological Systems. (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

  9. Notes on a PDE system for biological network formation

    KAUST Repository

    Haskovec, Jan


    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.

  10. Networks and network analysis for defence and security

    CERN Document Server

    Masys, Anthony J


    Networks and Network Analysis for Defence and Security discusses relevant theoretical frameworks and applications of network analysis in support of the defence and security domains. This book details real world applications of network analysis to support defence and security. Shocks to regional, national and global systems stemming from natural hazards, acts of armed violence, terrorism and serious and organized crime have significant defence and security implications. Today, nations face an uncertain and complex security landscape in which threats impact/target the physical, social, economic

  11. An novel frequent probability pattern mining algorithm based on circuit simulation method in uncertain biological networks (United States)


    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

  12. Transmission analysis in WDM networks

    DEFF Research Database (Denmark)

    Rasmussen, Christian Jørgen


    This thesis describes the development of a computer-based simulator for transmission analysis in optical wavelength division multiplexing networks. A great part of the work concerns fundamental optical network simulator issues. Among these issues are identification of the versatility and user...... of the onlinear Schrödinger equation. Adaptive step size split-step methods and a modified split-step method adapted for optical signals represented by several equivalent lowpass signals are developed. The work on the receiver model includes a fast method for computation of the time varying variance of the signal......-friendliness demands which such a simulator must meet, development of the "spectral window representation" for representation of the optical signals and finding an effective way of handling the optical signals in the computer memory. One important issue more is the rules for the determination of the order in which...

  13. Geostatistics and spatial analysis in biological anthropology. (United States)

    Relethford, John H


    A variety of methods have been used to make evolutionary inferences based on the spatial distribution of biological data, including reconstructing population history and detection of the geographic pattern of natural selection. This article provides an examination of geostatistical analysis, a method used widely in geology but which has not often been applied in biological anthropology. Geostatistical analysis begins with the examination of a variogram, a plot showing the relationship between a biological distance measure and the geographic distance between data points and which provides information on the extent and pattern of spatial correlation. The results of variogram analysis are used for interpolating values of unknown data points in order to construct a contour map, a process known as kriging. The methods of geostatistical analysis and discussion of potential problems are applied to a large data set of anthropometric measures for 197 populations in Ireland. The geostatistical analysis reveals two major sources of spatial variation. One pattern, seen for overall body and craniofacial size, shows an east-west cline most likely reflecting the combined effects of past population dispersal and settlement. The second pattern is seen for craniofacial height and shows an isolation by distance pattern reflecting rapid spatial changes in the midlands region of Ireland, perhaps attributable to the genetic impact of the Vikings. The correspondence of these results with other analyses of these data and the additional insights generated from variogram analysis and kriging illustrate the potential utility of geostatistical analysis in biological anthropology. (c) 2008 Wiley-Liss, Inc.

  14. MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links. (United States)

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


    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

  15. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach. (United States)

    Li, Jun; Zhao, Patrick X


    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

  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. (United States)

    Muldoon, Sarah Feldt


    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. CellNet: network biology applied to stem cell engineering. (United States)

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


    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.

  18. The promise of targeted proteomics for quantitative network biology. (United States)

    Matsumoto, Masaki; Nakayama, Keiichi I


    Proteomics is a powerful tool for obtaining information on a large number of proteins with regard to their expression levels, interactions with other molecules, and posttranslational modifications. Whereas nontargeted, discovery proteomics uncovers differences in the proteomic landscape under different conditions, targeted proteomics has been developed to overcome the limitations of this approach with regard to quantitation. In addition to technical advances in instruments and informatics tools, the advent of the synthetic proteome composed of synthetic peptides or recombinant proteins has advanced the adoption of targeted proteomics across a wide range of research fields. Targeted proteomics can now be applied to measurement of the dynamics of any proteins of interest under a variety of conditions as well as to estimation of the absolute abundance or stoichiometry of proteins in a given network. Multiplexed targeted proteomics assays of high reproducibility and accuracy can provide insight at the quantitative level into entire networks that govern biological phenomena or diseases. Such assays will establish a new paradigm for data-driven science. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Biologically plausible learning in neural networks with modulatory feedback. (United States)

    Grant, W Shane; Tanner, James; Itti, Laurent


    Although Hebbian learning has long been a key component in understanding neural plasticity, it has not yet been successful in modeling modulatory feedback connections, which make up a significant portion of connections in the brain. We develop a new learning rule designed around the complications of learning modulatory feedback and composed of three simple concepts grounded in physiologically plausible evidence. Using border ownership as a prototypical example, we show that a Hebbian learning rule fails to properly learn modulatory connections, while our proposed rule correctly learns a stimulus-driven model. To the authors' knowledge, this is the first time a border ownership network has been learned. Additionally, we show that the rule can be used as a drop-in replacement for a Hebbian learning rule to learn a biologically consistent model of orientation selectivity, a network which lacks any modulatory connections. Our results predict that the mechanisms we use are integral for learning modulatory connections in the brain and furthermore that modulatory connections have a strong dependence on inhibition. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. Social Network Analysis and informal trade

    DEFF Research Database (Denmark)

    Walther, Olivier

    networks can be applied to better understand informal trade in developing countries, with a particular focus on Africa. The paper starts by discussing some of the fundamental concepts developed by social network analysis. Through a number of case studies, we show how social network analysis can...... illuminate the relevant causes of social patterns, the impact of social ties on economic performance, the diffusion of resources and information, and the exercise of power. The paper then examines some of the methodological challenges of social network analysis and how it can be combined with other...... approaches. The paper finally highlights some of the applications of social network analysis and their implications for trade policies....

  1. Systems biology in physiology: the vasopressin signaling network in kidney. (United States)

    Knepper, Mark A


    Over the past 80 years, physiological research has moved progressively in a reductionist direction, providing mechanistic information on a smaller and smaller scale. This trend has culminated in the present focus on "molecular physiology," which deals with the function of single molecules responsible for cellular function. There is a need to assemble the information from the molecular level into models that explain physiological function at cellular, tissue, organ, and whole organism levels. Such integration is the major focus of an approach called "systems biology." The genome sequencing projects provide a basis for a new kind of systems biology called "data-rich" systems biology that is based on large-scale data acquisition methods including protein mass spectrometry, DNA microarrays, and deep sequencing of nucleic acids. These techniques allow investigators to measure thousands of variables simultaneously in response to an external stimulus. My laboratory is applying such an approach to the question: "How does the peptide hormone vasopressin regulate water permeability in the renal collecting duct?" We are using protein mass spectrometry to identify and quantify the phosphoproteome of collecting duct cells. The response to vasopressin, presented in the form of a network model, includes a general downregulation of proline-directed kinases (MAP kinases and cyclin-dependent kinases) and upregulation of basophilic kinases (ACG kinases and calmodulin-dependent kinases). Further progress depends on characterization and localization of candidate protein kinases in these families. The ultimate goal is to use multivariate statistical techniques and differential equations to obtain predictive models describing vasopressin signaling in the renal collecting duct.

  2. Topological Analysis of Urban Drainage Networks (United States)

    Yang, Soohyun; Paik, Kyungrock; McGrath, Gavan; Rao, Suresh


    Urban drainage networks are an essential component of infrastructure, and comprise the aggregation of underground pipe networks carrying storm water and domestic waste water for eventual discharge to natural stream networks. Growing urbanization has contributed to rapid expansion of sewer networks, vastly increasing their complexity and scale. Importance of sewer networks has been well studied from an engineering perspective, including resilient management, optimal design, and malfunctioning impact. Yet, analysis of the urban drainage networks using complex networks approach are lacking. Urban drainage networks consist of manholes and conduits, which correspond to nodes and edges, analogous to junctions and streams in river networks. Converging water flows in these two networks are driven by elevation gradient. In this sense, engineered urban drainage networks share several attributes of flows in river networks. These similarities between the two directed, converging flow networks serve the basis for us to hypothesize that the functional topology of sewer networks, like river networks, is scale-invariant. We analyzed the exceedance probability distribution of upstream area for practical sewer networks in South Korea. We found that the exceedance probability distributions of upstream area follow power-law, implying that the sewer networks exhibit topological self-similarity. The power-law exponents for the sewer networks were similar, and within the range reported from analysis of natural river networks. Thus, in line with our hypothesis, these results suggest that engineered urban drainage networks share functional topological attributes regardless of their structural dissimilarity or different underlying network evolution processes (natural vs. engineered). Implications of these findings for optimal design of sewer networks and for modeling sewer flows will be discussed.

  3. 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.


    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

  4. Arrays in biological and chemical analysis

    DEFF Research Database (Denmark)

    Christensen, Claus Bo Vöge


    Recently a dramatic change has happened for biological and biochemical analysis. Originally developed as an academic massive parallel screening tool, industry has caught the idea as well of performing all kinds of assays in the new format of microarrays. From food manufacturers over water supply...

  5. Review Essay: Does Qualitative Network Analysis Exist?

    Directory of Open Access Journals (Sweden)

    Rainer Diaz-Bone


    Full Text Available Social network analysis was formed and established in the 1970s as a way of analyzing systems of social relations. In this review the theoretical-methodological standpoint of social network analysis ("structural analysis" is introduced and the different forms of social network analysis are presented. Structural analysis argues that social actors and social relations are embedded in social networks, meaning that action and perception of actors as well as the performance of social relations are influenced by the network structure. Since the 1990s structural analysis has integrated concepts such as agency, discourse and symbolic orientation and in this way structural analysis has opened itself. Since then there has been increasing use of qualitative methods in network analysis. They are used to include the perspective of the analyzed actors, to explore networks, and to understand network dynamics. In the reviewed book, edited by Betina HOLLSTEIN and Florian STRAUS, the twenty predominantly empirically orientated contributions demonstrate the possibilities of combining quantitative and qualitative methods in network analyses in different research fields. In this review we examine how the contributions succeed in applying and developing the structural analysis perspective, and the self-positioning of "qualitative network analysis" is evaluated. URN: urn:nbn:de:0114-fqs0701287

  6. Google matrix analysis of directed networks (United States)

    Ermann, Leonardo; Frahm, Klaus M.; Shepelyansky, Dima L.


    In the past decade modern societies have developed enormous communication and social networks. Their classification and information retrieval processing has become a formidable task for the society. Because of the rapid growth of the World Wide Web, and social and communication networks, new mathematical methods have been invented to characterize the properties of these networks in a more detailed and precise way. Various search engines extensively use such methods. It is highly important to develop new tools to classify and rank a massive amount of network information in a way that is adapted to internal network structures and characteristics. This review describes the Google matrix analysis of directed complex networks demonstrating its efficiency using various examples including the World Wide Web, Wikipedia, software architectures, world trade, social and citation networks, brain neural networks, DNA sequences, and Ulam networks. The analytical and numerical matrix methods used in this analysis originate from the fields of Markov chains, quantum chaos, and random matrix theory.

  7. Prediction of Biological Motion Perception Performance from Intrinsic Brain Network Regional Efficiency (United States)

    Wang, Zengjian; Zhang, Delong; Liang, Bishan; Chang, Song; Pan, Jinghua; Huang, Ruiwang; Liu, Ming


    Biological motion perception (BMP) refers to the ability to perceive the moving form of a human figure from a limited amount of stimuli, such as from a few point lights located on the joints of a moving body. BMP is commonplace and important, but there is great inter-individual variability in this ability. This study used multiple regression model analysis to explore the association between BMP performance and intrinsic brain activity, in order to investigate the neural substrates underlying inter-individual variability of BMP performance. The resting-state functional magnetic resonance imaging (rs-fMRI) and BMP performance data were collected from 24 healthy participants, for whom intrinsic brain networks were constructed, and a graph-based network efficiency metric was measured. Then, a multiple linear regression model was used to explore the association between network regional efficiency and BMP performance. We found that the local and global network efficiency of many regions was significantly correlated with BMP performance. Further analysis showed that the local efficiency rather than global efficiency could be used to explain most of the BMP inter-individual variability, and the regions involved were predominately located in the Default Mode Network (DMN). Additionally, discrimination analysis showed that the local efficiency of certain regions such as the thalamus could be used to classify BMP performance across participants. Notably, the association pattern between network nodal efficiency and BMP was different from the association pattern of static directional/gender information perception. Overall, these findings show that intrinsic brain network efficiency may be considered a neural factor that explains BMP inter-individual variability. PMID:27853427

  8. Metabolic networks of Sodalis glossinidius: a systems biology approach to reductive evolution. (United States)

    Belda, Eugeni; Silva, Francisco J; Peretó, Juli; Moya, Andrés


    Genome reduction is a common evolutionary process affecting bacterial lineages that establish symbiotic or pathogenic associations with eukaryotic hosts. Such associations yield highly reduced genomes with greatly streamlined metabolic abilities shaped by the type of ecological association with the host. Sodalis glossinidius, the secondary endosymbiont of tsetse flies, represents one of the few complete genomes available of a bacterium at the initial stages of this process. In the present study, genome reduction is studied from a systems biology perspective through the reconstruction and functional analysis of genome-scale metabolic networks of S. glossinidius. The functional profile of ancestral and extant metabolic networks sheds light on the evolutionary events underlying transition to a host-dependent lifestyle. Meanwhile, reductive evolution simulations on the extant metabolic network can predict possible future evolution of S. glossinidius in the context of genome reduction. Finally, knockout simulations in different metabolic systems reveal a gradual decrease in network robustness to different mutational events for bacterial endosymbionts at different stages of the symbiotic association. Stoichiometric analysis reveals few gene inactivation events whose effects on the functionality of S. glossinidius metabolic systems are drastic enough to account for the ecological transition from a free-living to host-dependent lifestyle. The decrease in network robustness across different metabolic systems may be associated with the progressive integration in the more stable environment provided by the insect host. Finally, reductive evolution simulations reveal the strong influence that external conditions exert on the evolvability of metabolic systems.

  9. Process-driven inference of biological network structure: feasibility, minimality, and multiplicity.

    Directory of Open Access Journals (Sweden)

    Guanyu Wang

    Full Text Available A common problem in molecular biology is to use experimental data, such as microarray data, to infer knowledge about the structure of interactions between important molecules in subsystems of the cell. By approximating the state of each molecule as "on" or "off", it becomes possible to simplify the problem, and exploit the tools of boolean analysis for such inference. Amongst boolean techniques, the process-driven approach has shown promise in being able to identify putative network structures, as well as stability and modularity properties. This paper examines the process-driven approach more formally, and makes four contributions about the computational complexity of the inference problem, under the "dominant inhibition" assumption of molecular interactions. The first is a proof that the feasibility problem (does there exist a network that explains the data? can be solved in polynomial-time. Second, the minimality problem (what is the smallest network that explains the data? is shown to be NP-hard, and therefore unlikely to result in a polynomial-time algorithm. Third, a simple polynomial-time heuristic is shown to produce near-minimal solutions, as demonstrated by simulation. Fourth, the theoretical framework explains how multiplicity (the number of network solutions to realize a given biological process, which can take exponential-time to compute, can instead be accurately estimated by a fast, polynomial-time heuristic.

  10. Social network analysis community detection and evolution

    CERN Document Server

    Missaoui, Rokia


    This book is devoted to recent progress in social network analysis with a high focus on community detection and evolution. The eleven chapters cover the identification of cohesive groups, core components and key players either in static or dynamic networks of different kinds and levels of heterogeneity. Other important topics in social network analysis such as influential detection and maximization, information propagation, user behavior analysis, as well as network modeling and visualization are also presented. Many studies are validated through real social networks such as Twitter. This edit

  11. Iterative Systems Biology for Medicine – time for advancing from network signature to mechanistic equations

    KAUST Repository

    Gomez-Cabrero, David


    The rise and growth of Systems Biology following the sequencing of the human genome has been astounding. Early on, an iterative wet-dry methodology was formulated which turned out as a successful approach in deciphering biological complexity. Such type of analysis effectively identified and associated molecular network signatures operative in biological processes across different systems. Yet, it has proven difficult to distinguish between causes and consequences, thus making it challenging to attack medical questions where we require precise causative drug targets and disease mechanisms beyond a web of associated markers. Here we review principal advances with regard to identification of structure, dynamics, control, and design of biological systems, following the structure in the visionary review from 2002 by Dr. Kitano. Yet, here we find that the underlying challenge of finding the governing mechanistic system equations enabling precision medicine remains open thus rendering clinical translation of systems biology arduous. However, stunning advances in raw computational power, generation of high-precision multi-faceted biological data, combined with powerful algorithms hold promise to set the stage for data-driven identification of equations implicating a fundamental understanding of living systems during health and disease.

  12. Novel recurrent neural network for modelling biological networks: oscillatory p53 interaction dynamics. (United States)

    Ling, Hong; Samarasinghe, Sandhya; Kulasiri, Don


    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

  13. Network analysis literacy a practical approach to the analysis of networks

    CERN Document Server

    Zweig, Katharina A


    Network Analysis Literacy focuses on design principles for network analytics projects. The text enables readers to: pose a defined network analytic question; build a network to answer the question; choose or design the right network analytic methods for a particular purpose, and more.

  14. Social network analysis and dual rover communications (United States)

    Litaker, Harry L.; Howard, Robert L.


    Social network analysis (SNA) refers to the collection of techniques, tools, and methods used in sociometry aiming at the analysis of social networks to investigate decision making, group communication, and the distribution of information. Human factors engineers at the National Aeronautics and Space Administration (NASA) conducted a social network analysis on communication data collected during a 14-day field study operating a dual rover exploration mission to better understand the relationships between certain network groups such as ground control, flight teams, and planetary science. The analysis identified two communication network structures for the continuous communication and Twice-a-Day Communication scenarios as a split network and negotiated network respectfully. The major nodes or groups for the networks' architecture, transmittal status, and information were identified using graphical network mapping, quantitative analysis of subjective impressions, and quantified statistical analysis using Sociometric Statue and Centrality. Post-questionnaire analysis along with interviews revealed advantages and disadvantages of each network structure with team members identifying the need for a more stable continuous communication network, improved robustness of voice loops, and better systems training/capabilities for scientific imagery data and operational data during Twice-a-Day Communications.

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

    Directory of Open Access Journals (Sweden)

    Kato Mitsuru


    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

  16. Spatial-Frequency Azimuthally Stable Cartography of Biological Polycrystalline Networks

    Directory of Open Access Journals (Sweden)

    V. A. Ushenko


    Full Text Available A new azimuthally stable polarimetric technique processing microscopic images of optically anisotropic structures of biological tissues histological sections is proposed. It has been used as a generalized model of phase anisotropy definition of biological tissues by using superposition of Mueller matrices of linear birefringence and optical activity. The matrix element M44 has been chosen as the main information parameter, whose value is independent of the rotation angle of both sample and probing beam polarization plane. For the first time, the technique of concerted spatial-frequency filtration has been used in order to separate the manifestation of linear birefringence and optical activity. Thereupon, the method of azimuthally stable spatial-frequency cartography of biological tissues histological sections has been elaborated. As the analyzing tool, complex statistic, correlation, and fractal analysis of coordinate distributions of M44 element has been performed. The possibility of using the biopsy of the uterine wall tissue in order to differentiate benign (fibromyoma and malignant (adenocarcinoma conditions has been estimated.

  17. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    Gina Manda


    Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

  18. Understanding complex interactions using social network analysis. (United States)

    Pow, Janette; Gayen, Kaberi; Elliott, Lawrie; Raeside, Robert


    The aim of this paper is to raise the awareness of social network analysis as a method to facilitate research in nursing research. The application of social network analysis in assessing network properties has allowed greater insight to be gained in many areas including sociology, politics, business organisation and health care. However, the use of social networks in nursing has not received sufficient attention. Review of literature and illustration of the application of the method of social network analysis using research examples. First, the value of social networks will be discussed. Then by using illustrative examples, the value of social network analysis to nursing will be demonstrated. The method of social network analysis is found to give greater insights into social situations involving interactions between individuals and has particular application to the study of interactions between nurses and between nurses and patients and other actors. Social networks are systems in which people interact. Two quantitative techniques help our understanding of these networks. The first is visualisation of the network. The second is centrality. Individuals with high centrality are key communicators in a network. Applying social network analysis to nursing provides a simple method that helps gain an understanding of human interaction and how this might influence various health outcomes. It allows influential individuals (actors) to be identified. Their influence on the formation of social norms and communication can determine the extent to which new interventions or ways of thinking are accepted by a group. Thus, working with key individuals in a network could be critical to the success and sustainability of an intervention. Social network analysis can also help to assess the effectiveness of such interventions for the recipient and the service provider. © 2012 Blackwell Publishing Ltd.

  19. ProteoLens: a visual analytic tool for multi-scale database-driven biological network data mining. (United States)

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


    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

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

    Directory of Open Access Journals (Sweden)

    Liwei Zhuang


    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.

  1. Optimal synchronization in small-world biological neural networks with time-varying weights

    International Nuclear Information System (INIS)

    Zheng Hongyu; Luo Xiaoshu


    In this paper, a new model of small-world biological neural networks based on biophysical Hodgkin-Huxley neurons with time-varying weights is proposed. Then the synchronization phenomenon of small-world biological neural networks evoked by the learning rate is studied. The study shows that there exists an optimal synchronization state by changing the learning rate.

  2. Network Analysis on Attitudes : A Brief Tutorial

    NARCIS (Netherlands)

    Dalege, J.; Borsboom, D.; van Harreveld, F.; van der Maas, H.L.J.


    In this article, we provide a brief tutorial on the estimation, analysis, and simulation on attitude networks using the programming language R. We first discuss what a network is and subsequently show how one can estimate a regularized network on typical attitude data. For this, we use open-access

  3. Networks and Bargaining in Policy Analysis

    DEFF Research Database (Denmark)

    Bogason, Peter


    A duscussion of the fight between proponents of rationalistic policy analysis and more political interaction models for policy analysis. The latter group is the foundation for the many network models of policy analysis of today.......A duscussion of the fight between proponents of rationalistic policy analysis and more political interaction models for policy analysis. The latter group is the foundation for the many network models of policy analysis of today....

  4. Strategic Mobility 21: Rail Network Capacity Analysis

    National Research Council Canada - National Science Library

    Mallon, Lawrence G; Leachman, Robert C; Fetty, George R


    This analysis examined the rail network capacity and average transit times for commercial and surge military deployments through the proposed Victorville - Joint Power Projection Support Platform (JPPSP...

  5. Computer networks analysis with Cacti


    Gazvoda, Silvo


    In this thesis, we have identified techniques and approaches that are most commonly encountered in network management systems. We have described availability and performance monitoring techniques. Selection of monitoring technique depends on the complexity of monitored parameters and preliminary established architecture. Network monitoring suggests architecture in which centralized manager collects and analyses data from managed devices. Managed devices expose their network statistics through...

  6. Dynamic Network-Based Epistasis Analysis: Boolean Examples (United States)

    Azpeitia, Eugenio; Benítez, Mariana; Padilla-Longoria, Pablo; Espinosa-Soto, Carlos; Alvarez-Buylla, Elena R.


    In this article we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the inference of gene regulatory networks. Here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson, epistasis is defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus (herein, classical epistasis). Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct inference of gene interaction topologies is hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our article complements previous accounts, not only by focusing on the implications of the hierarchical and

  7. Egocentric social network analysis of pathological gambling. (United States)

    Meisel, Matthew K; Clifton, Allan D; Mackillop, James; Miller, Joshua D; Campbell, W Keith; Goodie, Adam S


    To apply social network analysis (SNA) to investigate whether frequency and severity of gambling problems were associated with different network characteristics among friends, family and co-workers is an innovative way to look at relationships among individuals; the current study was the first, to our knowledge, to apply SNA to gambling behaviors. Egocentric social network analysis was used to characterize formally the relationships between social network characteristics and gambling pathology. Laboratory-based questionnaire and interview administration. Forty frequent gamblers (22 non-pathological gamblers, 18 pathological gamblers) were recruited from the community. The SNA revealed significant social network compositional differences between the two groups: pathological gamblers (PGs) had more gamblers, smokers and drinkers in their social networks than did non-pathological gamblers (NPGs). PGs had more individuals in their network with whom they personally gambled, smoked and drank than those with who were NPG. Network ties were closer to individuals in their networks who gambled, smoked and drank more frequently. Associations between gambling severity and structural network characteristics were not significant. Pathological gambling is associated with compositional but not structural differences in social networks. Pathological gamblers differ from non-pathological gamblers in the number of gamblers, smokers and drinkers in their social networks. Homophily within the networks also indicates that gamblers tend to be closer with other gamblers. This homophily may serve to reinforce addictive behaviors, and may suggest avenues for future study or intervention. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  8. Network-based analysis of complex diseases. (United States)

    Liu, Z-P; Wang, Y; Zhang, X-S; Chen, L


    Complex diseases are commonly believed to be caused by the breakdown of several correlated genes rather than individual genes. The availability of genome-wide data of high-throughput experiments provides us with new opportunity to explore this hypothesis by analysing the disease-related biomolecular networks, which are expected to bridge genotypes and disease phenotypes and further reveal the biological mechanisms of complex diseases. In this study, the authors review the existing network biology efforts to study complex diseases, such as breast cancer, diabetes and Alzheimer's disease, using high-throughput data and computational tools. Specifically, the authors categorise these existing methods into several classes based on the research topics, that is, disease genes, dysfunctional pathways, network signatures and drug-target networks. The authors also summarise the pros and cons of those methods from both computation and application perspectives, and further discuss research trends and future topics of this promising field.

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

    Directory of Open Access Journals (Sweden)

    Primig Michael


    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.

  10. Social network analysis and supply chain management

    Directory of Open Access Journals (Sweden)

    Raúl Rodríguez Rodríguez


    Full Text Available This paper deals with social network analysis and how it could be integrated within supply chain management from a decision-making point of view. Even though the benefits of using social analysis have are widely accepted at both academic and industry/services context, there is still a lack of solid frameworks that allow decision-makers to connect the usage and obtained results of social network analysis – mainly both information and knowledge flows and derived results- with supply chain management objectives and goals. This paper gives an overview of social network analysis, the main social network analysis metrics, supply chain performance and, finally, it identifies how future frameworks could close the gap and link the results of social network analysis with the supply chain management decision-making processes.

  11. Network Analysis on Attitudes: A Brief Tutorial. (United States)

    Dalege, Jonas; Borsboom, Denny; van Harreveld, Frenk; van der Maas, Han L J


    In this article, we provide a brief tutorial on the estimation, analysis, and simulation on attitude networks using the programming language R. We first discuss what a network is and subsequently show how one can estimate a regularized network on typical attitude data. For this, we use open-access data on the attitudes toward Barack Obama during the 2012 American presidential election. Second, we show how one can calculate standard network measures such as community structure, centrality, and connectivity on this estimated attitude network. Third, we show how one can simulate from an estimated attitude network to derive predictions from attitude networks. By this, we highlight that network theory provides a framework for both testing and developing formalized hypotheses on attitudes and related core social psychological constructs.

  12. Social insect colony as a biological regulatory system: modelling information flow in dominance networks. (United States)

    Nandi, Anjan K; Sumana, Annagiri; Bhattacharya, Kunal


    Social insects provide an excellent platform to investigate flow of information in regulatory systems since their successful social organization is essentially achieved by effective information transfer through complex connectivity patterns among the colony members. Network representation of such behavioural interactions offers a powerful tool for structural as well as dynamical analysis of the underlying regulatory systems. In this paper, we focus on the dominance interaction networks in the tropical social wasp Ropalidia marginata-a species where behavioural observations indicate that such interactions are principally responsible for the transfer of information between individuals about their colony needs, resulting in a regulation of their own activities. Our research reveals that the dominance networks of R. marginata are structurally similar to a class of naturally evolved information processing networks, a fact confirmed also by the predominance of a specific substructure-the 'feed-forward loop'-a key functional component in many other information transfer networks. The dynamical analysis through Boolean modelling confirms that the networks are sufficiently stable under small fluctuations and yet capable of more efficient information transfer compared to their randomized counterparts. Our results suggest the involvement of a common structural design principle in different biological regulatory systems and a possible similarity with respect to the effect of selection on the organization levels of such systems. The findings are also consistent with the hypothesis that dominance behaviour has been shaped by natural selection to co-opt the information transfer process in such social insect species, in addition to its primal function of mediation of reproductive competition in the colony. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  13. 4th International Conference in Network Analysis

    CERN Document Server

    Koldanov, Petr; Pardalos, Panos


    The contributions in this volume cover a broad range of topics including maximum cliques, graph coloring, data mining, brain networks, Steiner forest, logistic and supply chain networks. Network algorithms and their applications to market graphs, manufacturing problems, internet networks and social networks are highlighted. The "Fourth International Conference in Network Analysis," held at the Higher School of Economics, Nizhny Novgorod in May 2014, initiated joint research between scientists, engineers and researchers from academia, industry and government; the major results of conference participants have been reviewed and collected in this Work. Researchers and students in mathematics, economics, statistics, computer science and engineering will find this collection a valuable resource filled with the latest research in network analysis.

  14. Students Mental Representation of Biology Diagrams/Pictures Conventions Based on Formation of Causal Network (United States)

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


    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.

  15. Collaboration Networks in the Brazilian Scientific Output in Evolutionary Biology: 2000-2012. (United States)

    Santin, Dirce M; Vanz, Samile A S; Stumpf, Ida R C


    This article analyzes the existing collaboration networks in the Brazilian scientific output in Evolutionary Biology, considering articles published during the period from 2000 to 2012 in journals indexed by Web of Science. The methodology integrates bibliometric techniques and Social Network Analysis resources to describe the growth of Brazilian scientific output and understand the levels, dynamics and structure of collaboration between authors, institutions and countries. The results unveil an enhancement and consolidation of collaborative relationships over time and suggest the existence of key institutions and authors, whose influence on research is expressed by the variety and intensity of the relationships established in the co-authorship of articles. International collaboration, present in more than half of the publications, is highly significant and unusual in Brazilian science. The situation indicates the internationalization of scientific output and the ability of the field to take part in the science produced by the international scientific community.

  16. Collaboration Networks in the Brazilian Scientific Output in Evolutionary Biology: 2000-2012

    Directory of Open Access Journals (Sweden)

    Dirce M. Santin


    Full Text Available This article analyzes the existing collaboration networks in the Brazilian scientific output in Evolutionary Biology, considering articles published during the period from 2000 to 2012 in journals indexed by Web of Science. The methodology integrates bibliometric techniques and Social Network Analysis resources to describe the growth of Brazilian scientific output and understand the levels, dynamics and structure of collaboration between authors, institutions and countries. The results unveil an enhancement and consolidation of collaborative relationships over time and suggest the existence of key institutions and authors, whose influence on research is expressed by the variety and intensity of the relationships established in the co-authorship of articles. International collaboration, present in more than half of the publications, is highly significant and unusual in Brazilian science. The situation indicates the internationalization of scientific output and the ability of the field to take part in the science produced by the international scientific community.

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

    DEFF Research Database (Denmark)

    Schoof, Erwin; Erler, Janine

    computational analysis, it is possible to gain a better understanding of colorectal cancer metastasis, and obtain potential clinical benefits. Chapter IV briefly summarizes the findings of the thesis and closes by proposing some future directions based on the work that was presented. Overall, the thesis aims...... a particular tumor, but also the phenotypic response to perturbations. Thus, there is a critical need for an integrative global approach, which assesses a biological system such as cancer from several molecular aspects in an un-biased fashion. This thesis summarizes the efforts that were undertaken as part...... of my PhD in an attempt to positively contribute to this fundamental challenge. The thesis is divided into four parts. In Chapter I, we introduce the complexity of cancer, and describe some underlying causes and ways to study the disease from different molecular perspectives. There is a nearly infinite...

  18. Interfacing a biosurveillance portal and an international network of institutional analysts to detect biological threats. (United States)

    Riccardo, Flavia; Shigematsu, Mika; Chow, Catherine; McKnight, C Jason; Linge, Jens; Doherty, Brian; Dente, Maria Grazia; Declich, Silvia; Barker, Mike; Barboza, Philippe; Vaillant, Laetitia; Donachie, Alastair; Mawudeku, Abla; Blench, Michael; Arthur, Ray


    The Early Alerting and Reporting (EAR) project, launched in 2008, is aimed at improving global early alerting and risk assessment and evaluating the feasibility and opportunity of integrating the analysis of biological, chemical, radionuclear (CBRN), and pandemic influenza threats. At a time when no international collaborations existed in the field of event-based surveillance, EAR's innovative approach involved both epidemic intelligence experts and internet-based biosurveillance system providers in the framework of an international collaboration called the Global Health Security Initiative, which involved the ministries of health of the G7 countries and Mexico, the World Health Organization, and the European Commission. The EAR project pooled data from 7 major internet-based biosurveillance systems onto a common portal that was progressively optimized for biological threat detection under the guidance of epidemic intelligence experts from public health institutions in Canada, the European Centre for Disease Prevention and Control, France, Germany, Italy, Japan, the United Kingdom, and the United States. The group became the first end users of the EAR portal, constituting a network of analysts working with a common standard operating procedure and risk assessment tools on a rotation basis to constantly screen and assess public information on the web for events that could suggest an intentional release of biological agents. Following the first 2-year pilot phase, the EAR project was tested in its capacity to monitor biological threats, proving that its working model was feasible and demonstrating the high commitment of the countries and international institutions involved. During the testing period, analysts using the EAR platform did not miss intentional events of a biological nature and did not issue false alarms. Through the findings of this initial assessment, this article provides insights into how the field of epidemic intelligence can advance through an



    Jerzy Szkutnik; Mariusz Kawecki


    Power distribution network analysis is taken into account. Based on correlation coefficient authors establish methodology of mathematical analysis useful in finding substations bear responsibility for power stoppage. Also methodology of risk assessment will be carried out.

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


    Wiwie, Christian; Rauch, Alexander; Haakonsson, Anders; Barrio-Hernandez, Inigo; Blagoev, Blagoy; Mandrup, Susanne; Röttger, Richard; Baumbach, Jan


    Advances in OMICS technologies emerged both massive expression data sets and huge networks modelling the molecular interplay of genes, RNAs, proteins and metabolites. Network enrichment methods combine these two data types to extract subnetwork responses from case/control setups. However, 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). I...

  1. Investigating biofuels through network analysis

    International Nuclear Information System (INIS)

    Curci, Ylenia; Mongeau Ospina, Christian A.


    Biofuel policies are motivated by a plethora of political concerns related to energy security, environmental damages, and support of the agricultural sector. In response to this, much scientific work has chiefly focussed on analysing the biofuel domain and on giving policy advice and recommendations. Although innovation has been acknowledged as one of the key factors in sustainable and cost-effective biofuel development, there is an urgent need to investigate technological trajectories in the biofuel sector by starting from consistent data and appropriate methodological tools. To do so, this work proposes a procedure to select patent data unequivocally related to the investigated sector, it uses co-occurrence of technological terms to compute patent similarity and highlights content and interdependencies of biofuels technological trajectories by revealing hidden topics from unstructured patent text fields. The analysis suggests that there is a breaking trend towards modern generation biofuels and that innovators seem to focus increasingly on the ability of alternative energy sources to adapt to the transport/industrial sector. - Highlights: • Innovative effort is devoted to biofuels additives and modern biofuels technologies. • A breaking trend can be observed from the second half of the last decade. • A patent network is identified via text mining techniques that extract latent topics.

  2. Ontology-supported research on vaccine efficacy, safety and integrative biological networks. (United States)

    He, Yongqun


    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.


    Silva, Ricardo; Heller, Katherine; Ghahramani, Zoubin; Airoldi, Edoardo M.


    Analogical reasoning depends fundamentally on the ability to learn and generalize about relations between objects. We develop an approach to relational learning which, given a set of pairs of objects S = {A(1) : B(1), A(2) : B(2), …, A(N) : B(N)}, measures how well other pairs A : B fit in with the set S. Our work addresses the following question: is the relation between objects A and B analogous to those relations found in S? Such questions are particularly relevant in information retrieval, where an investigator might want to search for analogous pairs of objects that match the query set of interest. There are many ways in which objects can be related, making the task of measuring analogies very challenging. Our approach combines a similarity measure on function spaces with Bayesian analysis to produce a ranking. It requires data containing features of the objects of interest and a link matrix specifying which relationships exist; no further attributes of such relationships are necessary. We illustrate the potential of our method on text analysis and information networks. An application on discovering functional interactions between pairs of proteins is discussed in detail, where we show that our approach can work in practice even if a small set of protein pairs is provided. PMID:24587838

  4. Endogenous Molecular-Cellular Network Cancer Theory: A Systems Biology Approach. (United States)

    Wang, Gaowei; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping


    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

  5. Biological neural networks as model systems for designing future parallel processing computers (United States)

    Ross, Muriel D.


    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.

  6. Weighted Complex Network Analysis of Pakistan Highways

    Directory of Open Access Journals (Sweden)

    Yasir Tariq Mohmand


    Full Text Available The structure and properties of public transportation networks have great implications in urban planning, public policies, and infectious disease control. This study contributes a weighted complex network analysis of travel routes on the national highway network of Pakistan. The network is responsible for handling 75 percent of the road traffic yet is largely inadequate, poor, and unreliable. The highway network displays small world properties and is assortative in nature. Based on the betweenness centrality of the nodes, the most important cities are identified as this could help in identifying the potential congestion points in the network. Keeping in view the strategic location of Pakistan, such a study is of practical importance and could provide opportunities for policy makers to improve the performance of the highway network.

  7. Analysis of deterministic cyclic gene regulatory network models with delays

    CERN Document Server

    Ahsen, Mehmet Eren; Niculescu, Silviu-Iulian


    This brief examines a deterministic, ODE-based model for gene regulatory networks (GRN) that incorporates nonlinearities and time-delayed feedback. An introductory chapter provides some insights into molecular biology and GRNs. The mathematical tools necessary for studying the GRN model are then reviewed, in particular Hill functions and Schwarzian derivatives. One chapter is devoted to the analysis of GRNs under negative feedback with time delays and a special case of a homogenous GRN is considered. Asymptotic stability analysis of GRNs under positive feedback is then considered in a separate chapter, in which conditions leading to bi-stability are derived. Graduate and advanced undergraduate students and researchers in control engineering, applied mathematics, systems biology and synthetic biology will find this brief to be a clear and concise introduction to the modeling and analysis of GRNs.

  8. Neural network for automatic analysis of motility data

    DEFF Research Database (Denmark)

    Jakobsen, Erik; Kruse-Andersen, S; Kolberg, Jens Godsk


    events. Due to great variation in events, this method often fails to detect biologically relevant pressure variations. We have tried to develop a new concept for recognition of pressure events based on a neural network. Pressures were recorded for over 23 hours in 29 normal volunteers by means...... comparable. However, the neural network recognized pressure peaks clearly generated by muscular activity that had escaped detection by the conventional program. In conclusion, we believe that neurocomputing has potential advantages for automatic analysis of gastrointestinal motility data....... of a portable data recording system. A number of pressure events and non-events were selected from 9 recordings and used for training the network. The performance of the trained network was then verified on recordings from the remaining 20 volunteers. The accuracy and sensitivity of the two systems were...

  9. Information theory applications for biological sequence analysis. (United States)

    Vinga, Susana


    Information theory (IT) addresses the analysis of communication systems and has been widely applied in molecular biology. In particular, alignment-free sequence analysis and comparison greatly benefited from concepts derived from IT, such as entropy and mutual information. This review covers several aspects of IT applications, ranging from genome global analysis and comparison, including block-entropy estimation and resolution-free metrics based on iterative maps, to local analysis, comprising the classification of motifs, prediction of transcription factor binding sites and sequence characterization based on linguistic complexity and entropic profiles. IT has also been applied to high-level correlations that combine DNA, RNA or protein features with sequence-independent properties, such as gene mapping and phenotype analysis, and has also provided models based on communication systems theory to describe information transmission channels at the cell level and also during evolutionary processes. While not exhaustive, this review attempts to categorize existing methods and to indicate their relation with broader transversal topics such as genomic signatures, data compression and complexity, time series analysis and phylogenetic classification, providing a resource for future developments in this promising area.

  10. Biological dosimetry by the triage dicentric chromosome assay - Further validation of international networking

    Energy Technology Data Exchange (ETDEWEB)

    Wilkins, Ruth C., E-mail: [Health Canada, Ottawa, ON K1A 0K9 (Canada); Romm, Horst; Oestreicher, Ursula [Bundesamt fur Strahlenschutz, 38226 Salzgitter (Germany); Marro, Leonora [Health Canada, Ottawa, ON K1A 0K9 (Canada); Yoshida, Mitsuaki A. [Biological Dosimetry Section, Dept. of Dose Assessment, Research Center for Radiation Emergency Medicine, NIRS, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Department Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564 (Japan); Suto, Y. [Biological Dosimetry Section, Dept. of Dose Assessment, Research Center for Radiation Emergency Medicine, NIRS, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Prasanna, Pataje G.S. [National Cancer Institute, Division of Cancer Treatment and Diagnosis, Radiation Research Program, 6130 Executive Blvd., MSC 7440, Bethesda, MD 20892-7440 (United States)


    Biological dosimetry is an essential tool for estimating radiation doses received to personnel when physical dosimetry is not available or inadequate. The current preferred biodosimetry method is based on the measurement of radiation-specific dicentric chromosomes in exposed individuals' peripheral blood lymphocytes. However, this method is labor-, time- and expertise-demanding. Consequently, for mass casualty applications, strategies have been developed to increase its throughput. One such strategy is to develop validated cytogenetic biodosimetry laboratory networks, both national and international. In a previous study, the dicentric chromosome assay (DCA) was validated in our cytogenetic biodosimetry network involving five geographically dispersed laboratories. A complementary strategy to further enhance the throughput of the DCA among inter-laboratory networks is to use a triage DCA where dose assessments are made by truncating the labor-demanding and time-consuming metaphase spread analysis to 20 - 50 metaphase spreads instead of routine 500 - 1000 metaphase spread analysis. Our laboratory network also validated this triage DCA, however, these dose estimates were made using calibration curves generated in each laboratory from the blood samples irradiated in a single laboratory. In an emergency situation, dose estimates made using pre-existing calibration curves which may vary according to radiation type and dose rate and therefore influence the assessed dose. Here, we analyze the effect of using a pre-existing calibration curve on assessed dose among our network laboratories. The dose estimates were made by analyzing 1000 metaphase spreads as well as triage quality scoring and compared to actual physical doses applied to the samples for validation. The dose estimates in the laboratory partners were in good agreement with the applied physical doses and determined to be adequate for guidance in the treatment of acute radiation syndrome.

  11. NEAT: an efficient network enrichment analysis test. (United States)

    Signorelli, Mirko; Vinciotti, Veronica; Wit, Ernst C


    Network enrichment analysis is a powerful method, which allows to integrate gene enrichment analysis with the information on relationships between genes that is provided by gene networks. Existing tests for network enrichment analysis deal only with undirected networks, they can be computationally slow and are based on normality assumptions. We propose NEAT, a test for network enrichment analysis. The test is based on the hypergeometric distribution, which naturally arises as the null distribution in this context. NEAT can be applied not only to undirected, but to directed and partially directed networks as well. Our simulations indicate that NEAT is considerably faster than alternative resampling-based methods, and that its capacity to detect enrichments is at least as good as the one of alternative tests. We discuss applications of NEAT to network analyses in yeast by testing for enrichment of the Environmental Stress Response target gene set with GO Slim and KEGG functional gene sets, and also by inspecting associations between functional sets themselves. NEAT is a flexible and efficient test for network enrichment analysis that aims to overcome some limitations of existing resampling-based tests. The method is implemented in the R package neat, which can be freely downloaded from CRAN ( ).

  12. Network approaches to the functional analysis of microbial proteins. (United States)

    Hallinan, J S; James, K; Wipat, A


    Large amounts of detailed biological data have been generated over the past few decades. Much of these data is freely available in over 1000 online databases; an enticing, but frustrating resource for microbiologists interested in a systems-level view of the structure and function of microbial cells. The frustration engendered by the need to trawl manually through hundreds of databases in order to accumulate information about a gene, protein, pathway, or organism of interest can be alleviated by the use of computational data integration to generated network views of the system of interest. Biological networks can be constructed from a single type of data, such as protein-protein binding information, or from data generated by multiple experimental approaches. In an integrated network, nodes usually represent genes or gene products, while edges represent some form of interaction between the nodes. Edges between nodes may be weighted to represent the probability that the edge exists in vivo. Networks may also be enriched with ontological annotations, facilitating both visual browsing and computational analysis via web service interfaces. In this review, we describe the construction, analysis of both single-data source and integrated networks, and their application to the inference of protein function in microbes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Industrial entrepreneurial network: Structural and functional analysis (United States)

    Medvedeva, M. A.; Davletbaev, R. H.; Berg, D. B.; Nazarova, J. J.; Parusheva, S. S.


    Structure and functioning of two model industrial entrepreneurial networks are investigated in the present paper. One of these networks is forming when implementing an integrated project and consists of eight agents, which interact with each other and external environment. The other one is obtained from the municipal economy and is based on the set of the 12 real business entities. Analysis of the networks is carried out on the basis of the matrix of mutual payments aggregated over the certain time period. The matrix is created by the methods of experimental economics. Social Network Analysis (SNA) methods and instruments were used in the present research. The set of basic structural characteristics was investigated: set of quantitative parameters such as density, diameter, clustering coefficient, different kinds of centrality, and etc. They were compared with the random Bernoulli graphs of the corresponding size and density. Discovered variations of random and entrepreneurial networks structure are explained by the peculiarities of agents functioning in production network. Separately, were identified the closed exchange circuits (cyclically closed contours of graph) forming an autopoietic (self-replicating) network pattern. The purpose of the functional analysis was to identify the contribution of the autopoietic network pattern in its gross product. It was found that the magnitude of this contribution is more than 20%. Such value allows using of the complementary currency in order to stimulate economic activity of network agents.

  14. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering. (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V


    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

  15. A statistical framework for differential network analysis from microarray data

    Directory of Open Access Journals (Sweden)

    Datta Somnath


    Full Text Available Abstract Background It has been long well known that genes do not act alone; rather groups of genes act in consort during a biological process. Consequently, the expression levels of genes are dependent on each other. Experimental techniques to detect such interacting pairs of genes have been in place for quite some time. With the advent of microarray technology, newer computational techniques to detect such interaction or association between gene expressions are being proposed which lead to an association network. While most microarray analyses look for genes that are differentially expressed, it is of potentially greater significance to identify how entire association network structures change between two or more biological settings, say normal versus diseased cell types. Results We provide a recipe for conducting a differential analysis of networks constructed from microarray data under two experimental settings. At the core of our approach lies a connectivity score that represents the strength of genetic association or interaction between two genes. We use this score to propose formal statistical tests for each of following queries: (i whether the overall modular structures of the two networks are different, (ii whether the connectivity of a particular set of "interesting genes" has changed between the two networks, and (iii whether the connectivity of a given single gene has changed between the two networks. A number of examples of this score is provided. We carried out our method on two types of simulated data: Gaussian networks and networks based on differential equations. We show that, for appropriate choices of the connectivity scores and tuning parameters, our method works well on simulated data. We also analyze a real data set involving normal versus heavy mice and identify an interesting set of genes that may play key roles in obesity. Conclusions Examining changes in network structure can provide valuable information about the

  16. 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.


    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)

  17. 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: [Comision Chilena de Energia, Amutanegui 95, Santiago Centro, Santiago (Chile)


    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)

  18. 3rd International Conference on Network Analysis

    CERN Document Server

    Kalyagin, Valery; Pardalos, Panos


    This volume compiles the major results of conference participants from the "Third International Conference in Network Analysis" held at the Higher School of Economics, Nizhny Novgorod in May 2013, with the aim to initiate further joint research among different groups. The contributions in this book cover a broad range of topics relevant to the theory and practice of network analysis, including the reliability of complex networks, software, theory, methodology, and applications.  Network analysis has become a major research topic over the last several years. The broad range of applications that can be described and analyzed by means of a network has brought together researchers, practitioners from numerous fields such as operations research, computer science, transportation, energy, biomedicine, computational neuroscience and social sciences. In addition, new approaches and computer environments such as parallel computing, grid computing, cloud computing, and quantum computing have helped to solve large scale...

  19. Social network analysis in medical education. (United States)

    Isba, Rachel; Woolf, Katherine; Hanneman, Robert


    Humans are fundamentally social beings. The social systems within which we live our lives (families, schools, workplaces, professions, friendship groups) have a significant influence on our health, success and well-being. These groups can be characterised as networks and analysed using social network analysis. Social network analysis is a mainly quantitative method for analysing how relationships between individuals form and affect those individuals, but also how individual relationships build up into wider social structures that influence outcomes at a group level. Recent increases in computational power have increased the accessibility of social network analysis methods for application to medical education research. Social network analysis has been used to explore team-working, social influences on attitudes and behaviours, the influence of social position on individual success, and the relationship between social cohesion and power. This makes social network analysis theories and methods relevant to understanding the social processes underlying academic performance, workplace learning and policy-making and implementation in medical education contexts. Social network analysis is underused in medical education, yet it is a method that could yield significant insights that would improve experiences and outcomes for medical trainees and educators, and ultimately for patients. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

  20. Transcription regulatory networks analysis using CAGE

    KAUST Repository

    Tegnér, Jesper N.


    Mapping out cellular networks in general and transcriptional networks in particular has proved to be a bottle-neck hampering our understanding of biological processes. Integrative approaches fusing computational and experimental technologies for decoding transcriptional networks at a high level of resolution is therefore of uttermost importance. Yet, this is challenging since the control of gene expression in eukaryotes is a complex multi-level process influenced by several epigenetic factors and the fine interplay between regulatory proteins and the promoter structure governing the combinatorial regulation of gene expression. In this chapter we review how the CAGE data can be integrated with other measurements such as expression, physical interactions and computational prediction of regulatory motifs, which together can provide a genome-wide picture of eukaryotic transcriptional regulatory networks at a new level of resolution. © 2010 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

  1. MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems. (United States)

    Herranz, Héctor; Cohen, Stephen M


    Biological systems are continuously challenged by an environment that is variable. Yet, a key feature of developmental and physiological processes is their remarkable stability. This review considers how microRNAs contribute to gene regulatory networks that confer robustness.

  2. Analysis of complex networks using aggressive abstraction.

    Energy Technology Data Exchange (ETDEWEB)

    Colbaugh, Richard; Glass, Kristin.; Willard, Gerald


    This paper presents a new methodology for analyzing complex networks in which the network of interest is first abstracted to a much simpler (but equivalent) representation, the required analysis is performed using the abstraction, and analytic conclusions are then mapped back to the original network and interpreted there. We begin by identifying a broad and important class of complex networks which admit abstractions that are simultaneously dramatically simplifying and property preserving we call these aggressive abstractions -- and which can therefore be analyzed using the proposed approach. We then introduce and develop two forms of aggressive abstraction: 1.) finite state abstraction, in which dynamical networks with uncountable state spaces are modeled using finite state systems, and 2.) onedimensional abstraction, whereby high dimensional network dynamics are captured in a meaningful way using a single scalar variable. In each case, the property preserving nature of the abstraction process is rigorously established and efficient algorithms are presented for computing the abstraction. The considerable potential of the proposed approach to complex networks analysis is illustrated through case studies involving vulnerability analysis of technological networks and predictive analysis for social processes.

  3. Benchmark analysis of railway networks and undertakings

    NARCIS (Netherlands)

    Hansen, I.A.; Wiggenraad, P.B.L.; Wolff, J.W.


    Benchmark analysis of railway networks and companies has been stimulated by the European policy of deregulation of transport markets, the opening of national railway networks and markets to new entrants and separation of infrastructure and train operation. Recent international railway benchmarking

  4. Consistency analysis of network traffic repositories

    NARCIS (Netherlands)

    Lastdrager, Elmer; Lastdrager, E.E.H.; Pras, Aiko

    Traffic repositories with TCP/IP header information are very important for network analysis. Researchers often assume that such repositories reliably represent all traffic that has been flowing over the network; little thoughts are made regarding the consistency of these repositories. Still, for

  5. Social Network Analysis and Critical Realism

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert


    Social network analysis ( SNA) is an increasingly popular approach that provides researchers with highly developed tools to map and analyze complexes of social relations. Although a number of network scholars have explicated the assumptions that underpin SNA, the approach has yet to be discussed ...

  6. Commentary: Biochemistry and Molecular Biology Educators Launch National Network (United States)

    Bailey, Cheryl; Bell, Ellis; Johnson, Margaret; Mattos, Carla; Sears, Duane; White, Harold B.


    The American Society of Biochemistry and Molecular Biology (ASBMB) has launched an National Science Foundation (NSF)-funded 5 year project to support biochemistry and molecular biology educators learning what and how students learn. As a part of this initiative, hundreds of life scientists will plan and develop a rich central resource for…

  7. Boolean Factor Analysis by Attractor Neural Network

    Czech Academy of Sciences Publication Activity Database

    Frolov, A. A.; Húsek, Dušan; Muraviev, I. P.; Polyakov, P.Y.


    Roč. 18, č. 3 (2007), s. 698-707 ISSN 1045-9227 R&D Projects: GA AV ČR 1ET100300419; GA ČR GA201/05/0079 Institutional research plan: CEZ:AV0Z10300504 Keywords : recurrent neural network * Hopfield-like neural network * associative memory * unsupervised learning * neural network architecture * neural network application * statistics * Boolean factor analysis * dimensionality reduction * features clustering * concepts search * information retrieval Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.769, year: 2007

  8. SNAP: A General Purpose Network Analysis and Graph Mining Library (United States)

    Leskovec, Jure; Sosič, Rok


    Large networks are becoming a widely used abstraction for studying complex systems in a broad set of disciplines, ranging from social network analysis to molecular biology and neuroscience. Despite an increasing need to analyze and manipulate large networks, only a limited number of tools are available for this task. Here, we describe Stanford Network Analysis Platform (SNAP), a general-purpose, high-performance system that provides easy to use, high-level operations for analysis and manipulation of large networks. We present SNAP functionality, describe its implementational details, and give performance benchmarks. SNAP has been developed for single big-memory machines and it balances the trade-off between maximum performance, compact in-memory graph representation, and the ability to handle dynamic graphs where nodes and edges are being added or removed over time. SNAP can process massive networks with hundreds of millions of nodes and billions of edges. SNAP offers over 140 different graph algorithms that can efficiently manipulate large graphs, calculate structural properties, generate regular and random graphs, and handle attributes and meta-data on nodes and edges. Besides being able to handle large graphs, an additional strength of SNAP is that networks and their attributes are fully dynamic, they can be modified during the computation at low cost. SNAP is provided as an open source library in C++ as well as a module in Python. We also describe the Stanford Large Network Dataset, a set of social and information real-world networks and datasets, which we make publicly available. The collection is a complementary resource to our SNAP software and is widely used for development and benchmarking of graph analytics algorithms. PMID:28344853

  9. SNAP: A General Purpose Network Analysis and Graph Mining Library. (United States)

    Leskovec, Jure; Sosič, Rok


    Large networks are becoming a widely used abstraction for studying complex systems in a broad set of disciplines, ranging from social network analysis to molecular biology and neuroscience. Despite an increasing need to analyze and manipulate large networks, only a limited number of tools are available for this task. Here, we describe Stanford Network Analysis Platform (SNAP), a general-purpose, high-performance system that provides easy to use, high-level operations for analysis and manipulation of large networks. We present SNAP functionality, describe its implementational details, and give performance benchmarks. SNAP has been developed for single big-memory machines and it balances the trade-off between maximum performance, compact in-memory graph representation, and the ability to handle dynamic graphs where nodes and edges are being added or removed over time. SNAP can process massive networks with hundreds of millions of nodes and billions of edges. SNAP offers over 140 different graph algorithms that can efficiently manipulate large graphs, calculate structural properties, generate regular and random graphs, and handle attributes and meta-data on nodes and edges. Besides being able to handle large graphs, an additional strength of SNAP is that networks and their attributes are fully dynamic, they can be modified during the computation at low cost. SNAP is provided as an open source library in C++ as well as a module in Python. We also describe the Stanford Large Network Dataset, a set of social and information real-world networks and datasets, which we make publicly available. The collection is a complementary resource to our SNAP software and is widely used for development and benchmarking of graph analytics algorithms.

  10. Spectrum-Based and Collaborative Network Topology Analysis and Visualization (United States)

    Hu, Xianlin


    Networks are of significant importance in many application domains, such as World Wide Web and social networks, which often embed rich topological information. Since network topology captures the organization of network nodes and links, studying network topology is very important to network analysis. In this dissertation, we study networks by…

  11. Network analysis of human glaucomatous optic nerve head astrocytes

    Directory of Open Access Journals (Sweden)

    Bhattacharya Sanjoy K


    Full Text Available Abstract Background Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive. Methods To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs. Results Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by genetic analysis can be functionally interconnected into one epistatic network via experimentally-validated interactions. Finally, we built and analyzed an integrative disease pathology network from a combined set of genes revealed in genetic studies, genes differentially expressed in glaucoma and closely connected genes/proteins in the interactome. Conclusion Our results suggest several key biological network modules that are involved in regulating neurotoxicity of reactive astrocytes in glaucoma, and comprise potential targets for cell-based therapy.

  12. Analysis and Testing of Mobile Wireless Networks (United States)

    Alena, Richard; Evenson, Darin; Rundquist, Victor; Clancy, Daniel (Technical Monitor)


    Wireless networks are being used to connect mobile computing elements in more applications as the technology matures. There are now many products (such as 802.11 and 802.11b) which ran in the ISM frequency band and comply with wireless network standards. They are being used increasingly to link mobile Intranet into Wired networks. Standard methods of analyzing and testing their performance and compatibility are needed to determine the limits of the technology. This paper presents analytical and experimental methods of determining network throughput, range and coverage, and interference sources. Both radio frequency (BE) domain and network domain analysis have been applied to determine wireless network throughput and range in the outdoor environment- Comparison of field test data taken under optimal conditions, with performance predicted from RF analysis, yielded quantitative results applicable to future designs. Layering multiple wireless network- sooners can increase performance. Wireless network components can be set to different radio frequency-hopping sequences or spreading functions, allowing more than one sooner to coexist. Therefore, we ran multiple 802.11-compliant systems concurrently in the same geographical area to determine interference effects and scalability, The results can be used to design of more robust networks which have multiple layers of wireless data communication paths and provide increased throughput overall.

  13. A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology. (United States)

    Chen, Bor-Sen; Lin, Ying-Po


    Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at 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 enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, 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 systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view.

  14. NEXCADE: perturbation analysis for complex networks.

    Directory of Open Access Journals (Sweden)

    Gitanjali Yadav

    Full Text Available Recent advances in network theory have led to considerable progress in our understanding of complex real world systems and their behavior in response to external threats or fluctuations. Much of this research has been invigorated by demonstration of the 'robust, yet fragile' nature of cellular and large-scale systems transcending biology, sociology, and ecology, through application of the network theory to diverse interactions observed in nature such as plant-pollinator, seed-dispersal agent and host-parasite relationships. In this work, we report the development of NEXCADE, an automated and interactive program for inducing disturbances into complex systems defined by networks, focusing on the changes in global network topology and connectivity as a function of the perturbation. NEXCADE uses a graph theoretical approach to simulate perturbations in a user-defined manner, singly, in clusters, or sequentially. To demonstrate the promise it holds for broader adoption by the research community, we provide pre-simulated examples from diverse real-world networks including eukaryotic protein-protein interaction networks, fungal biochemical networks, a variety of ecological food webs in nature as well as social networks. NEXCADE not only enables network visualization at every step of the targeted attacks, but also allows risk assessment, i.e. identification of nodes critical for the robustness of the system of interest, in order to devise and implement context-based strategies for restructuring a network, or to achieve resilience against link or node failures. Source code and license for the software, designed to work on a Linux-based operating system (OS can be downloaded at In addition, we have developed NEXCADE as an OS-independent online web server freely available to the scientific community without any login requirement at

  15. NEXCADE: perturbation analysis for complex networks. (United States)

    Yadav, Gitanjali; Babu, Suresh


    Recent advances in network theory have led to considerable progress in our understanding of complex real world systems and their behavior in response to external threats or fluctuations. Much of this research has been invigorated by demonstration of the 'robust, yet fragile' nature of cellular and large-scale systems transcending biology, sociology, and ecology, through application of the network theory to diverse interactions observed in nature such as plant-pollinator, seed-dispersal agent and host-parasite relationships. In this work, we report the development of NEXCADE, an automated and interactive program for inducing disturbances into complex systems defined by networks, focusing on the changes in global network topology and connectivity as a function of the perturbation. NEXCADE uses a graph theoretical approach to simulate perturbations in a user-defined manner, singly, in clusters, or sequentially. To demonstrate the promise it holds for broader adoption by the research community, we provide pre-simulated examples from diverse real-world networks including eukaryotic protein-protein interaction networks, fungal biochemical networks, a variety of ecological food webs in nature as well as social networks. NEXCADE not only enables network visualization at every step of the targeted attacks, but also allows risk assessment, i.e. identification of nodes critical for the robustness of the system of interest, in order to devise and implement context-based strategies for restructuring a network, or to achieve resilience against link or node failures. Source code and license for the software, designed to work on a Linux-based operating system (OS) can be downloaded at In addition, we have developed NEXCADE as an OS-independent online web server freely available to the scientific community without any login requirement at

  16. Complex Network Analysis of Guangzhou Metro

    Directory of Open Access Journals (Sweden)

    Yasir Tariq Mohmand


    Full Text Available The structure and properties of public transportation networks can provide suggestions for urban planning and public policies. This study contributes a complex network analysis of the Guangzhou metro. The metro network has 236 kilometers of track and is the 6th busiest metro system of the world. In this paper topological properties of the network are explored. We observed that the network displays small world properties and is assortative in nature. The network possesses a high average degree of 17.5 with a small diameter of 5. Furthermore, we also identified the most important metro stations based on betweenness and closeness centralities. These could help in identifying the probable congestion points in the metro system and provide policy makers with an opportunity to improve the performance of the metro system.

  17. Extending Stochastic Network Calculus to Loss Analysis

    Directory of Open Access Journals (Sweden)

    Chao Luo


    Full Text Available Loss is an important parameter of Quality of Service (QoS. Though stochastic network calculus is a very useful tool for performance evaluation of computer networks, existing studies on stochastic service guarantees mainly focused on the delay and backlog. Some efforts have been made to analyse loss by deterministic network calculus, but there are few results to extend stochastic network calculus for loss analysis. In this paper, we introduce a new parameter named loss factor into stochastic network calculus and then derive the loss bound through the existing arrival curve and service curve via this parameter. We then prove that our result is suitable for the networks with multiple input flows. Simulations show the impact of buffer size, arrival traffic, and service on the loss factor.

  18. Computer network environment planning and analysis (United States)

    Dalphin, John F.


    The GSFC Computer Network Environment provides a broadband RF cable between campus buildings and ethernet spines in buildings for the interlinking of Local Area Networks (LANs). This system provides terminal and computer linkage among host and user systems thereby providing E-mail services, file exchange capability, and certain distributed computing opportunities. The Environment is designed to be transparent and supports multiple protocols. Networking at Goddard has a short history and has been under coordinated control of a Network Steering Committee for slightly more than two years; network growth has been rapid with more than 1500 nodes currently addressed and greater expansion expected. A new RF cable system with a different topology is being installed during summer 1989; consideration of a fiber optics system for the future will begin soon. Summmer study was directed toward Network Steering Committee operation and planning plus consideration of Center Network Environment analysis and modeling. Biweekly Steering Committee meetings were attended to learn the background of the network and the concerns of those managing it. Suggestions for historical data gathering have been made to support future planning and modeling. Data Systems Dynamic Simulator, a simulation package developed at NASA and maintained at GSFC was studied as a possible modeling tool for the network environment. A modeling concept based on a hierarchical model was hypothesized for further development. Such a model would allow input of newly updated parameters and would provide an estimation of the behavior of the network.

  19. Statistical Analysis of Bus Networks in India. (United States)

    Chatterjee, Atanu; Manohar, Manju; Ramadurai, Gitakrishnan


    In this paper, we model the bus networks of six major Indian cities as graphs in L-space, and evaluate their various statistical properties. While airline and railway networks have been extensively studied, a comprehensive study on the structure and growth of bus networks is lacking. In India, where bus transport plays an important role in day-to-day commutation, it is of significant interest to analyze its topological structure and answer basic questions on its evolution, growth, robustness and resiliency. Although the common feature of small-world property is observed, our analysis reveals a wide spectrum of network topologies arising due to significant variation in the degree-distribution patterns in the networks. We also observe that these networks although, robust and resilient to random attacks are particularly degree-sensitive. Unlike real-world networks, such as Internet, WWW and airline, that are virtual, bus networks are physically constrained. Our findings therefore, throw light on the evolution of such geographically and constrained networks that will help us in designing more efficient bus networks in the future.

  20. Constructing an Intelligent Patent Network Analysis Method

    Directory of Open Access Journals (Sweden)

    Chao-Chan Wu


    Full Text Available Patent network analysis, an advanced method of patent analysis, is a useful tool for technology management. This method visually displays all the relationships among the patents and enables the analysts to intuitively comprehend the overview of a set of patents in the field of the technology being studied. Although patent network analysis possesses relative advantages different from traditional methods of patent analysis, it is subject to several crucial limitations. To overcome the drawbacks of the current method, this study proposes a novel patent analysis method, called the intelligent patent network analysis method, to make a visual network with great precision. Based on artificial intelligence techniques, the proposed method provides an automated procedure for searching patent documents, extracting patent keywords, and determining the weight of each patent keyword in order to generate a sophisticated visualization of the patent network. This study proposes a detailed procedure for generating an intelligent patent network that is helpful for improving the efficiency and quality of patent analysis. Furthermore, patents in the field of Carbon Nanotube Backlight Unit (CNT-BLU were analyzed to verify the utility of the proposed method.

  1. Techniques for Intelligence Analysis of Networks

    National Research Council Canada - National Science Library

    Cares, Jeffrey R


    ...) there are significant intelligence analysis manifestations of these properties; and (4) a more satisfying theory of Networked Competition than currently exists for NCW/NCO is emerging from this research...

  2. A network biology approach to understanding the importance of chameleon proteins in human physiology and pathology. (United States)

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Marashi, Sayed-Amir


    Chameleon proteins are proteins which include sequences that can adopt α-helix-β-strand (HE-chameleon) or α-helix-coil (HC-chameleon) or β-strand-coil (CE-chameleon) structures to operate their crucial biological functions. In this study, using a network-based approach, we examined the chameleon proteins to give a better knowledge on these proteins. We focused on proteins with identical chameleon sequences with more than or equal to seven residues long in different PDB entries, which adopt HE-chameleon, HC-chameleon, and CE-chameleon structures in the same protein. One hundred and ninety-one human chameleon proteins were identified via our in-house program. Then, protein-protein interaction (PPI) networks, Gene ontology (GO) enrichment, disease network, and pathway enrichment analyses were performed for our derived data set. We discovered that there are chameleon sequences which reside in protein-protein interaction regions between two proteins critical for their dual function. Analysis of the PPI networks for chameleon proteins introduced five hub proteins, namely TP53, EGFR, HSP90AA1, PPARA, and HIF1A, which were presented in four PPI clusters. The outcomes demonstrate that the chameleon regions are in critical domains of these proteins and are important in the development and treatment of human cancers. The present report is the first network-based functional study of chameleon proteins using computational approaches and might provide a new perspective for understanding the mechanisms of diseases helping us in developing new medical therapies along with discovering new proteins with chameleon properties which are highly important in cancer.

  3. Dynamic network-based epistasis analysis: Boolean examples

    Directory of Open Access Journals (Sweden)

    Eugenio eAzpeitia


    Full Text Available In this review we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the topologies of gene interactions infered. This has been acknowledged in several previous papers and reviews, but here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson (herein, classical epistasis, defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus. Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct gene interaction topologies are hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our review complements previous accounts, not

  4. Biological Sabatier reaction with CFD analysis (United States)

    Leonzio, Grazia


    The biological Sabatier reaction is a suitable option for the future energy storage. In this research a computational fluid dynamics analysis is carried out to study the mixing inside the anaerobic digester, to evaluate the gas to liquid mass transfer and the efficiency of the reaction. A detailed modeling about the hydrodynamics and mixing is developed: the standard k-ɛ mixture turbulence model and the Eulerian-Eulerian approach are used to simulate the flow inside the anaerobic digestion. The system mixing uses external sludge re-circulating pumps. Results of simulations show that with higher liquid velocity there are higher mass to transfer from gas to liquid and turbulent dissipation rate. The future construction of the anaerobic digester will provide the obtained results.

  5. Multilayer motif analysis of brain networks (United States)

    Battiston, Federico; Nicosia, Vincenzo; Chavez, Mario; Latora, Vito


    In the last decade, network science has shed new light both on the structural (anatomical) and on the functional (correlations in the activity) connectivity among the different areas of the human brain. The analysis of brain networks has made possible to detect the central areas of a neural system and to identify its building blocks by looking at overabundant small subgraphs, known as motifs. However, network analysis of the brain has so far mainly focused on anatomical and functional networks as separate entities. The recently developed mathematical framework of multi-layer networks allows us to perform an analysis of the human brain where the structural and functional layers are considered together. In this work, we describe how to classify the subgraphs of a multiplex network, and we extend the motif analysis to networks with an arbitrary number of layers. We then extract multi-layer motifs in brain networks of healthy subjects by considering networks with two layers, anatomical and functional, respectively, obtained from diffusion and functional magnetic resonance imaging. Results indicate that subgraphs in which the presence of a physical connection between brain areas (links at the structural layer) coexists with a non-trivial positive correlation in their activities are statistically overabundant. Finally, we investigate the existence of a reinforcement mechanism between the two layers by looking at how the probability to find a link in one layer depends on the intensity of the connection in the other one. Showing that functional connectivity is non-trivially constrained by the underlying anatomical network, our work contributes to a better understanding of the interplay between the structure and function in the human brain.

  6. Social Network Analysis Identifies Key Participants in Conservation Development. (United States)

    Farr, Cooper M; Reed, Sarah E; Pejchar, Liba


    Understanding patterns of participation in private lands conservation, which is often implemented voluntarily by individual citizens and private organizations, could improve its effectiveness at combating biodiversity loss. We used social network analysis (SNA) to examine participation in conservation development (CD), a private land conservation strategy that clusters houses in a small portion of a property while preserving the remaining land as protected open space. Using data from public records for six counties in Colorado, USA, we compared CD participation patterns among counties and identified actors that most often work with others to implement CDs. We found that social network characteristics differed among counties. The network density, or proportion of connections in the network, varied from fewer than 2 to nearly 15%, and was higher in counties with smaller populations and fewer CDs. Centralization, or the degree to which connections are held disproportionately by a few key actors, was not correlated strongly with any county characteristics. Network characteristics were not correlated with the prevalence of wildlife-friendly design features in CDs. The most highly connected actors were biological and geological consultants, surveyors, and engineers. Our work demonstrates a new application of SNA to land-use planning, in which CD network patterns are examined and key actors are identified. For better conservation outcomes of CD, we recommend using network patterns to guide strategies for outreach and information dissemination, and engaging with highly connected actor types to encourage widespread adoption of best practices for CD design and stewardship.

  7. Network Analysis of Time-Lapse Microscopy Recordings

    Directory of Open Access Journals (Sweden)

    Erik eSmedler


    Full Text Available Multicellular organisms rely on intercellular communication to regulate important cellular processes critical to life. To further our understanding of those processes there is a need to scrutinize dynamical signaling events and their functions in both cells and organisms. Here, we report a method and provide MATLAB code that analyzes time-lapse microscopy recordings to identify and characterize network structures within large cell populations, such as interconnected neurons. The approach is demonstrated using intracellular calcium (Ca2+ recordings in neural progenitors and cardiac myocytes, but could be applied to a wide variety of biosensors employed in diverse cell types and organisms. In this method, network structures are analyzed by applying cross-correlation signal processing and graph theory to single-cell recordings. The goal of the analysis is to determine if the single cell activity constitutes a network of interconnected cells and to decipher the properties of this network. The method can be applied in many fields of biology in which biosensors are used to monitor signaling events in living cells. Analyzing intercellular communication in cell ensembles can reveal essential network structures that provide important biological insights.

  8. Network-based analysis reveals distinct association patterns in a semantic MEDLINE-based drug-disease-gene network. (United States)

    Zhang, Yuji; Tao, Cui; Jiang, Guoqian; Nair, Asha A; Su, Jian; Chute, Christopher G; Liu, Hongfang


    A huge amount of associations among different biological entities (e.g., disease, drug, and gene) are scattered in millions of biomedical articles. Systematic analysis of such heterogeneous data can infer novel associations among different biological entities in the context of personalized medicine and translational research. Recently, network-based computational approaches have gained popularity in investigating such heterogeneous data, proposing novel therapeutic targets and deciphering disease mechanisms. However, little effort has been devoted to investigating associations among drugs, diseases, and genes in an integrative manner. We propose a novel network-based computational framework to identify statistically over-expressed subnetwork patterns, called network motifs, in an integrated disease-drug-gene network extracted from Semantic MEDLINE. The framework consists of two steps. The first step is to construct an association network by extracting pair-wise associations between diseases, drugs and genes in Semantic MEDLINE using a domain pattern driven strategy. A Resource Description Framework (RDF)-linked data approach is used to re-organize the data to increase the flexibility of data integration, the interoperability within domain ontologies, and the efficiency of data storage. Unique associations among drugs, diseases, and genes are extracted for downstream network-based analysis. The second step is to apply a network-based approach to mine the local network structure of this heterogeneous network. Significant network motifs are then identified as the backbone of the network. A simplified network based on those significant motifs is then constructed to facilitate discovery. We implemented our computational framework and identified five network motifs, each of which corresponds to specific biological meanings. Three case studies demonstrate that novel associations are derived from the network topology analysis of reconstructed networks of significant

  9. SECLAF: A Webserver and Deep Neural Network Design Tool for Hierarchical Biological Sequence Classification. (United States)

    Szalkai, Balázs; Grolmusz, Vince


    Artificial intelligence (AI) tools are gaining more and more ground each year in bioinformatics. Learning algorithms can be taught for specific tasks by using the existing enormous biological databases, and the resulting models can be used for the high-quality classification of novel, un-categorized data in numerous areas, including biological sequence analysis. Here we introduce SECLAF, a webserver that uses deep neural networks for hierarchical biological sequence classification. By applying SECLAF for residue-sequences, we have reported (Methods (2018), the most accurate multi-label protein classifier to date (UniProt -into 698 classes- AUC 99.99%; Gene Ontology -into 983 classes- AUC 99.45%). Our framework SECLAF can be applied for other sequence classification tasks, as we describe in the present contribution. The program SECLAF is implemented in Python, and is available for download, with example datasets at the website For Gene Ontology and UniProt based classifications a webserver is also available at the address above. and

  10. Historical Network Analysis of the Web

    DEFF Research Database (Denmark)

    Brügger, Niels


    This article discusses some of the fundamental methodological challenges related to doing historical network analyses of the web based on material in web archives. Since the late 1990s many countries have established extensive national web archives, and software supported network analysis...... of the online web has for a number of years gained currency within Internet studies. However, the combination of these two phenomena—historical network analysis of material in web archives—can at best be characterized as an emerging new area of study. Most of the methodological challenges within this new area...... revolve around the specific nature of archived web material. On the basis of an introduction to the processes involved in web archiving as well as of the characteristics of archived web material, the article outlines and scrutinizes some of the major challenges which may arise when doing network analysis...

  11. Visualization and Analysis of Complex Covert Networks

    DEFF Research Database (Denmark)

    Memon, Bisharat

    This report discusses and summarize the results of my work so far in relation to my Ph.D. project entitled "Visualization and Analysis of Complex Covert Networks". The focus of my research is primarily on development of methods and supporting tools for visualization and analysis of networked......-users (intelligence analysts) in harvesting, filtering, storing, managing, structuring, mining, analyzing, interpreting, and visualizing data about offensive networks. The methods and tools proposed and discussed in this work can also be applied to analysis of more generic complex networks....... systems that are covert and hence inherently complex. My Ph.D. is positioned within the wider framework of CrimeFighter project. The framework envisions a number of key knowledge management processes that are involved in the workflow, and the toolbox provides supporting tools to assist human end...

  12. Organ-on-a-Chip: New Platform for Biological Analysis

    Directory of Open Access Journals (Sweden)

    Fan An


    Full Text Available Direct detection and analysis of biomolecules and cells in physiological microenvironment is urgently needed for fast evaluation of biology and pharmacy. The past several years have witnessed remarkable development opportunities in vitro organs and tissues models with multiple functions based on microfluidic devices, termed as “organ-on-a-chip”. Briefly speaking, it is a promising technology in rebuilding physiological functions of tissues and organs, featuring mammalian cell co-culture and artificial microenvironment created by microchannel networks. In this review, we summarized the advances in studies of heart-, vessel-, liver-, neuron-, kidney- and Multi-organs-on-a-chip, and discussed some noteworthy potential on-chip detection schemes.

  13. Reliability analysis with Bayesian networks


    Zwirglmaier, Kilian Martin


    Bayesian networks (BNs) represent a probabilistic modeling tool with large potential for reliability engineering. While BNs have been successfully applied to reliability engineering, there are remaining issues, some of which are addressed in this work. Firstly a classification of BN elicitation approaches is proposed. Secondly two approximate inference approaches, one of which is based on discretization and the other one on sampling, are proposed. These approaches are applicable to hybrid/con...

  14. Automatic compilation from high-level biologically-oriented programming language to genetic regulatory networks. (United States)

    Beal, Jacob; Lu, Ting; Weiss, Ron


    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.

  15. The International Trade Network: weighted network analysis and modelling

    International Nuclear Information System (INIS)

    Bhattacharya, K; Mukherjee, G; Manna, S S; Saramäki, J; Kaski, K


    Tools of the theory of critical phenomena, namely the scaling analysis and universality, are argued to be applicable to large complex web-like network structures. Using a detailed analysis of the real data of the International Trade Network we argue that the scaled link weight distribution has an approximate log-normal distribution which remains robust over a period of 53 years. Another universal feature is observed in the power-law growth of the trade strength with gross domestic product, the exponent being similar for all countries. Using the 'rich-club' coefficient measure of the weighted networks it has been shown that the size of the rich-club controlling half of the world's trade is actually shrinking. While the gravity law is known to describe well the social interactions in the static networks of population migration, international trade, etc, here for the first time we studied a non-conservative dynamical model based on the gravity law which excellently reproduced many empirical features of the ITN

  16. Differential network analysis with multiply imputed lipidomic data.

    Directory of Open Access Journals (Sweden)

    Maiju Kujala

    Full Text Available The importance of lipids for cell function and health has been widely recognized, e.g., a disorder in the lipid composition of cells has been related to atherosclerosis caused cardiovascular disease (CVD. Lipidomics analyses are characterized by large yet not a huge number of mutually correlated variables measured and their associations to outcomes are potentially of a complex nature. Differential network analysis provides a formal statistical method capable of inferential analysis to examine differences in network structures of the lipids under two biological conditions. It also guides us to identify potential relationships requiring further biological investigation. We provide a recipe to conduct permutation test on association scores resulted from partial least square regression with multiple imputed lipidomic data from the LUdwigshafen RIsk and Cardiovascular Health (LURIC study, particularly paying attention to the left-censored missing values typical for a wide range of data sets in life sciences. Left-censored missing values are low-level concentrations that are known to exist somewhere between zero and a lower limit of quantification. To make full use of the LURIC data with the missing values, we utilize state of the art multiple imputation techniques and propose solutions to the challenges that incomplete data sets bring to differential network analysis. The customized network analysis helps us to understand the complexities of the underlying biological processes by identifying lipids and lipid classes that interact with each other, and by recognizing the most important differentially expressed lipids between two subgroups of coronary artery disease (CAD patients, the patients that had a fatal CVD event and the ones who remained stable during two year follow-up.

  17. BinAligner: a heuristic method to align biological networks. (United States)

    Yang, Jialiang; Li, Jun; Grünewald, Stefan; Wan, Xiu-Feng


    The advances in high throughput omics technologies have made it possible to characterize molecular interactions within and across various species. Alignments and comparison of molecular networks across species will help detect orthologs and conserved functional modules and provide insights on the evolutionary relationships of the compared species. However, such analyses are not trivial due to the complexity of network and high computational cost. Here we develop a mixture of global and local algorithm, BinAligner, for network alignments. Based on the hypotheses that the similarity between two vertices across networks would be context dependent and that the information from the edges and the structures of subnetworks can be more informative than vertices alone, two scoring schema, 1-neighborhood subnetwork and graphlet, were introduced to derive the scoring matrices between networks, besides the commonly used scoring scheme from vertices. Then the alignment problem is formulated as an assignment problem, which is solved by the combinatorial optimization algorithm, such as the Hungarian method. The proposed algorithm was applied and validated in aligning the protein-protein interaction network of Kaposi's sarcoma associated herpesvirus (KSHV) and that of varicella zoster virus (VZV). Interestingly, we identified several putative functional orthologous proteins with similar functions but very low sequence similarity between the two viruses. For example, KSHV open reading frame 56 (ORF56) and VZV ORF55 are helicase-primase subunits with sequence identity 14.6%, and KSHV ORF75 and VZV ORF44 are tegument proteins with sequence identity 15.3%. These functional pairs can not be identified if one restricts the alignment into orthologous protein pairs. In addition, BinAligner identified a conserved pathway between two viruses, which consists of 7 orthologous protein pairs and these proteins are connected by conserved links. This pathway might be crucial for virus packing and

  18. The Stochastic Evolutionary Game for a Population of Biological Networks Under Natural Selection (United States)

    Chen, Bor-Sen; Ho, Shih-Ju


    In this study, a population of evolutionary biological networks is described by a stochastic dynamic system with intrinsic random parameter fluctuations due to genetic variations and external disturbances caused by environmental changes in the evolutionary process. Since information on environmental changes is unavailable and their occurrence is unpredictable, they can be considered as a game player with the potential to destroy phenotypic stability. The biological network needs to develop an evolutionary strategy to improve phenotypic stability as much as possible, so it can be considered as another game player in the evolutionary process, ie, a stochastic Nash game of minimizing the maximum network evolution level caused by the worst environmental disturbances. Based on the nonlinear stochastic evolutionary game strategy, we find that some genetic variations can be used in natural selection to construct negative feedback loops, efficiently improving network robustness. This provides larger genetic robustness as a buffer against neutral genetic variations, as well as larger environmental robustness to resist environmental disturbances and maintain a network phenotypic traits in the evolutionary process. In this situation, the robust phenotypic traits of stochastic biological networks can be more frequently selected by natural selection in evolution. However, if the harbored neutral genetic variations are accumulated to a sufficiently large degree, and environmental disturbances are strong enough that the network robustness can no longer confer enough genetic robustness and environmental robustness, then the phenotype robustness might break down. In this case, a network phenotypic trait may be pushed from one equilibrium point to another, changing the phenotypic trait and starting a new phase of network evolution through the hidden neutral genetic variations harbored in network robustness by adaptive evolution. Further, the proposed evolutionary game is extended to

  19. Development of Network Analysis and Visualization System for KEGG Pathways

    Directory of Open Access Journals (Sweden)

    Dongmin Seo


    Full Text Available Big data refers to informationalization technology for extracting valuable information through the use and analysis of large-scale data and, based on that data, deriving plans for response or predicting changes. With the development of software and devices for next generation sequencing, a vast amount of bioinformatics data has been generated recently. Also, bioinformatics data based big-data technology is rising rapidly as a core technology by the bioinformatician, biologist and big-data scientist. KEGG pathway is bioinformatics data for understanding high-level functions and utilities of the biological system. However, KEGG pathway analysis requires a lot of time and effort because KEGG pathways are high volume and very diverse. In this paper, we proposed a network analysis and visualization system that crawl user interest KEGG pathways, construct a pathway network based on a hierarchy structure of pathways and visualize relations and interactions of pathways by clustering and selecting core pathways from the network. Finally, we construct a pathway network collected by starting with an Alzheimer’s disease pathway and show the results on clustering and selecting core pathways from the pathway network.

  20. Information theory in systems biology. Part I: Gene regulatory and metabolic networks. (United States)

    Mousavian, Zaynab; Kavousi, Kaveh; Masoudi-Nejad, Ali


    "A Mathematical Theory of Communication", was published in 1948 by Claude Shannon to establish a framework that is now known as information theory. In recent decades, information theory has gained much attention in the area of systems biology. The aim of this paper is to provide a systematic review of those contributions that have applied information theory in inferring or understanding of biological systems. Based on the type of system components and the interactions between them, we classify the biological systems into 4 main classes: gene regulatory, metabolic, protein-protein interaction and signaling networks. In the first part of this review, we attempt to introduce most of the existing studies on two types of biological networks, including gene regulatory and metabolic networks, which are founded on the concepts of information theory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Network Anomaly Detection Based on Wavelet Analysis

    Directory of Open Access Journals (Sweden)

    Ali A. Ghorbani


    Full Text Available Signal processing techniques have been applied recently for analyzing and detecting network anomalies due to their potential to find novel or unknown intrusions. In this paper, we propose a new network signal modelling technique for detecting network anomalies, combining the wavelet approximation and system identification theory. In order to characterize network traffic behaviors, we present fifteen features and use them as the input signals in our system. We then evaluate our approach with the 1999 DARPA intrusion detection dataset and conduct a comprehensive analysis of the intrusions in the dataset. Evaluation results show that the approach achieves high-detection rates in terms of both attack instances and attack types. Furthermore, we conduct a full day's evaluation in a real large-scale WiFi ISP network where five attack types are successfully detected from over 30 millions flows.

  2. Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data

    NARCIS (Netherlands)

    Kümmel, Anne; Panke, Sven; Heinemann, Matthias


    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

  3. Network graph analysis of gene-gene interactions in genome-wide association study data. (United States)

    Lee, Sungyoung; Kwon, Min-Seok; Park, Taesung


    Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene (GxG) interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

  4. Bernstein approximations in glasso-based estimation of biological networks

    NARCIS (Netherlands)

    Purutcuoglu, Vilda; Agraz, Melih; Wit, Ernst

    The Gaussian graphical model (GGM) is one of the common dynamic modelling approaches in the construction of gene networks. In inference of this modelling the interaction between genes can be detected mainly via graphical lasso (glasso) or coordinate descent-based approaches. Although these methods

  5. A network biology model of micronutrient related health

    NARCIS (Netherlands)

    Ommen, B. van; Fairweather-Tait, S.; Freidig, A.; Kardinaal, A.; Scalbert, A.; Wopereis, S.


    Micronutrients are involved in specific biochemical pathways and have dedicated functions in the body, but they are also interconnected in complex metabolic networks, such as oxidative-reductive and inflammatory pathways and hormonal regulation, in which the overarching function is to optimise

  6. Integration of biological networks and gene expression data using Cytoscape

    DEFF Research Database (Denmark)

    Cline, M.S.; Smoot, M.; Cerami, E.


    Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an ...

  7. Biologically Inspired Target Recognition in Radar Sensor Networks

    Directory of Open Access Journals (Sweden)

    Liang Qilian


    Full Text Available One of the great mysteries of the brain is cognitive control. How can the interactions between millions of neurons result in behavior that is coordinated and appears willful and voluntary? There is consensus that it depends on the prefrontal cortex (PFC. Many PFC areas receive converging inputs from at least two sensory modalities. Inspired by human's innate ability to process and integrate information from disparate, network-based sources, we apply human-inspired information integration mechanisms to target detection in cognitive radar sensor network. Humans' information integration mechanisms have been modelled using maximum-likelihood estimation (MLE or soft-max approaches. In this paper, we apply these two algorithms to cognitive radar sensor networks target detection. Discrete-cosine-transform (DCT is used to process the integrated data from MLE or soft-max. We apply fuzzy logic system (FLS to automatic target detection based on the AC power values from DCT. Simulation results show that our MLE-DCT-FLS and soft-max-DCT-FLS approaches perform very well in the radar sensor network target detection, whereas the existing 2D construction algorithm does not work in this study.

  8. Importance of randomness in biological networks: A random matrix ...

    Indian Academy of Sciences (India)


    Jan 29, 2015 ... Random matrix theory, initially proposed to understand the complex interactions in nuclear spectra, has demonstrated its success in diverse domains of science ranging from quantum chaos to galaxies. We demonstrate the applicability of random matrix theory for networks by providing a new dimension to ...

  9. [RESAOLAB: West African network of laboratories to enhance the quality of clinical biology]. (United States)

    Delorme, L; Machuron, J L; Sow, I; Diagne, R; Sakandé, J; Nikiéma, A; Bougoudogo, F; Keita, A; Longuet, C


    The Fondation Mérieux, in partnership with the Ministries of Health of Burkina Faso, Mali and Senegal, implemented for four years a project to reinforce the laboratory sector in the three participating countries: the RESAOLAB project (West African Network of Biomedical Analysis Laboratories).The objective of RESAOLAB project, in partnership with the WHO Office for West Africa and the West African Health Organization, was to strengthen the systems of biomedical laboratories to improve diagnostic services, access, monitoring and management of infectious diseases. Following the successful results achieved under the RESAOLAB project and due to the demand of the neighbour countries ministries, the RESAOLAB project is now extended to four other countries of the West African region: Benin, Guinea-Conakry, Niger and Togo. The RESAOLAB project has become the RESAOLAB programme, its purpose is to strengthen the quality of the medical biology services thanks to a regional and transversal approach.

  10. Social network analysis applied to team sports analysis

    CERN Document Server

    Clemente, Filipe Manuel; Mendes, Rui Sousa


    Explaining how graph theory and social network analysis can be applied to team sports analysis, This book presents useful approaches, models and methods that can be used to characterise the overall properties of team networks and identify the prominence of each team player. Exploring the different possible network metrics that can be utilised in sports analysis, their possible applications and variances from situation to situation, the respective chapters present an array of illustrative case studies. Identifying the general concepts of social network analysis and network centrality metrics, readers are shown how to generate a methodological protocol for data collection. As such, the book provides a valuable resource for students of the sport sciences, sports engineering, applied computation and the social sciences.

  11. Biological oscillations for learning walking coordination: dynamic recurrent neural network functionally models physiological central pattern generator. (United States)

    Hoellinger, Thomas; Petieau, Mathieu; Duvinage, Matthieu; Castermans, Thierry; Seetharaman, Karthik; Cebolla, Ana-Maria; Bengoetxea, Ana; Ivanenko, Yuri; Dan, Bernard; Cheron, Guy


    The existence of dedicated neuronal modules such as those organized in the cerebral cortex, thalamus, basal ganglia, cerebellum, or spinal cord raises the question of how these functional modules are coordinated for appropriate motor behavior. Study of human locomotion offers an interesting field for addressing this central question. The coordination of the elevation of the 3 leg segments under a planar covariation rule (Borghese et al., 1996) was recently modeled (Barliya et al., 2009) by phase-adjusted simple oscillators shedding new light on the understanding of the central pattern generator (CPG) processing relevant oscillation signals. We describe the use of a dynamic recurrent neural network (DRNN) mimicking the natural oscillatory behavior of human locomotion for reproducing the planar covariation rule in both legs at different walking speeds. Neural network learning was based on sinusoid signals integrating frequency and amplitude features of the first three harmonics of the sagittal elevation angles of the thigh, shank, and foot of each lower limb. We verified the biological plausibility of the neural networks. Best results were obtained with oscillations extracted from the first three harmonics in comparison to oscillations outside the harmonic frequency peaks. Physiological replication steadily increased with the number of neuronal units from 1 to 80, where similarity index reached 0.99. Analysis of synaptic weighting showed that the proportion of inhibitory connections consistently increased with the number of neuronal units in the DRNN. This emerging property in the artificial neural networks resonates with recent advances in neurophysiology of inhibitory neurons that are involved in central nervous system oscillatory activities. The main message of this study is that this type of DRNN may offer a useful model of physiological central pattern generator for gaining insights in basic research and developing clinical applications.

  12. Collaborative Approach to Network Behavior Analysis (United States)

    Rehak, Martin; Pechoucek, Michal; Grill, Martin; Bartos, Karel; Celeda, Pavel; Krmicek, Vojtech

    Network Behavior Analysis techniques are designed to detect intrusions and other undesirable behavior in computer networks by analyzing the traffic statistics. We present an efficient framework for integration of anomaly detection algorithms working on the identical input data. This framework is based on high-speed network traffic acquisition subsystem and on trust modeling, a well-established set of techniques from the multi-agent system field. Trust-based integration of algorithms results in classification with lower error rate, especially in terms of false positives. The presented framework is suitable for both online and offline processing, and introduces a relatively low computational overhead compared to deployment of isolated anomaly detection algorithms.

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

    Directory of Open Access Journals (Sweden)

    Jim Harkin


    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.

  14. Comparative Analysis of Computer Network Security Scanners

    Directory of Open Access Journals (Sweden)

    Victor Sergeevich Gorbatov


    Full Text Available The paper is devoted to the analysis of the problem of comparison of security scanners computer network. A common comprehensive assessment of security control is developed on the base of comparative analysis of data security controls. We have tested security scanners available on the market.

  15. Modeling Wireless Sensor Networks for Monitoring in Biological Processes

    DEFF Research Database (Denmark)

    Nadimi, Esmaeil

    (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...... 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...... signal strength). Fusing the two measured behavioral data resulted in an improvement of the classification results regarding the animal behavior mode (activity/inactivity), compared to the results achieved by only monitoring one of the behavioral parameters. Applying a multiple-model adaptive estimation...

  16. Hierarchical analysis of dependency in metabolic networks. (United States)

    Gagneur, Julien; Jackson, David B; Casari, Georg


    Elucidation of metabolic networks for an increasing number of organisms reveals that even small networks can contain thousands of reactions and chemical species. The intimate connectivity between components complicates their decomposition into biologically meaningful sub-networks. Moreover, traditional higher-order representations of metabolic networks as metabolic pathways, suffers from the lack of rigorous definition, yielding pathways of disparate content and size. We introduce a hierarchical representation that emphasizes the gross organization of metabolic networks in largely independent pathways and sub-systems at several levels of independence. The approach highlights the coupling of different pathways and the shared compounds responsible for those couplings. By assessing our results on Escherichia coli (E.coli metabolic reactions, Genetic Circuits Research Group, University of California, San Diego,, 'model v 1.01. reactions') against accepted biochemical annotations, we provide the first systematic synopsis of an organism's metabolism. Comparison with operons of E.coli shows that low-level clusters are reflected in genome organization and gene regulation. Source code, data sets and supplementary information are available at

  17. Neutron scattering for the analysis of biological structures. Brookhaven symposia in biology. Number 27

    Energy Technology Data Exchange (ETDEWEB)

    Schoenborn, B P [ed.


    Sessions were included on neutron scattering and biological structure analysis, protein crystallography, neutron scattering from oriented systems, solution scattering, preparation of deuterated specimens, inelastic scattering, data analysis, experimental techniques, and instrumentation. Separate entries were made for the individual papers.

  18. Network Analysis in Community Psychology: Looking Back, Looking Forward


    Neal, Zachary P.; Neal, Jennifer Watling


    Highlights Network analysis is ideally suited for community psychology research because it focuses on context. Use of network analysis in community psychology is growing. Network analysis in community psychology has employed some potentially problematic practices. Recommended practices are identified to improve network analysis in community psychology.

  19. Topological Data Analysis of Biological Aggregation Models (United States)

    Topaz, Chad M.; Ziegelmeier, Lori; Halverson, Tom


    We apply tools from topological data analysis to two mathematical models inspired by biological aggregations such as bird flocks, fish schools, and insect swarms. Our data consists of numerical simulation output from the models of Vicsek and D'Orsogna. These models are dynamical systems describing the movement of agents who interact via alignment, attraction, and/or repulsion. Each simulation time frame is a point cloud in position-velocity space. We analyze the topological structure of these point clouds, interpreting the persistent homology by calculating the first few Betti numbers. These Betti numbers count connected components, topological circles, and trapped volumes present in the data. To interpret our results, we introduce a visualization that displays Betti numbers over simulation time and topological persistence scale. We compare our topological results to order parameters typically used to quantify the global behavior of aggregations, such as polarization and angular momentum. The topological calculations reveal events and structure not captured by the order parameters. PMID:25970184

  20. Biological Implications of Dynamical Phases in Non-equilibrium Networks (United States)

    Murugan, Arvind; Vaikuntanathan, Suriyanarayanan


    Biology achieves novel functions like error correction, ultra-sensitivity and accurate concentration measurement at the expense of free energy through Maxwell Demon-like mechanisms. The design principles and free energy trade-offs have been studied for a variety of such mechanisms. In this review, we emphasize a perspective based on dynamical phases that can explain commonalities shared by these mechanisms. Dynamical phases are defined by typical trajectories executed by non-equilibrium systems in the space of internal states. We find that coexistence of dynamical phases can have dramatic consequences for function vs free energy cost trade-offs. Dynamical phases can also provide an intuitive picture of the design principles behind such biological Maxwell Demons.

  1. A swarm intelligence framework for reconstructing gene networks: searching for biologically plausible architectures. (United States)

    Kentzoglanakis, Kyriakos; Poole, Matthew


    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.

  2. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

    NARCIS (Netherlands)

    He, F.; Murabito, E.; Westerhoff, H.V.


    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental


    Darabos, Christian; Qiu, Jingya; Moore, Jason H


    Complex diseases are the result of intricate interactions between genetic, epigenetic and environmental factors. In previous studies, we used epidemiological and genetic data linking environmental exposure or genetic variants to phenotypic disease to construct Human Phenotype Networks and separately analyze the effects of both environment and genetic factors on disease interactions. To better capture the intricacies of the interactions between environmental exposure and the biological pathways in complex disorders, we integrate both aspects into a single "tripartite" network. Despite extensive research, the mechanisms by which chemical agents disrupt biological pathways are still poorly understood. In this study, we use our integrated network model to identify specific biological pathway candidates possibly disrupted by environmental agents. We conjecture that a higher number of co-occurrences between an environmental substance and biological pathway pair can be associated with a higher likelihood that the substance is involved in disrupting that pathway. We validate our model by demonstrating its ability to detect known arsenic and signal transduction pathway interactions and speculate on candidate cell-cell junction organization pathways disrupted by cadmium. The validation was supported by distinct publications of cell biology and genetic studies that associated environmental exposure to pathway disruption. The integrated network approach is a novel method for detecting the biological effects of environmental exposures. A better understanding of the molecular processes associated with specific environmental exposures will help in developing targeted molecular therapies for patients who have been exposed to the toxicity of environmental chemicals.

  4. FUSE: a profit maximization approach for functional summarization of biological networks. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Seah Boon-Siew


    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.

  6. Context, Cognition, and Biology in Applied Behavior Analysis. (United States)

    Morris, Edward K.

    Behavior analysts are having their professional identities challenged by the roles that cognition and biology are said to play in the conduct and outcome of applied behavior analysis and behavior therapy. For cogniphiliacs, cognition and biology are central to their interventions because cognition and biology are said to reflect various processes,…

  7. An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks. (United States)

    Botía, Juan A; Vandrovcova, Jana; Forabosco, Paola; Guelfi, Sebastian; D'Sa, Karishma; Hardy, John; Lewis, Cathryn M; Ryten, Mina; Weale, Michael E


    Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, ). We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data. We observed substantially improved module properties, including: (1) few or zero misplaced genes; (2) increased counts of replicable clusters in alternate tissues (x3.1 on average); (3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate partitions in simulated data according to a range of similarity indices. The results obtained from our investigations indicate that our k-means method, applied as an adjunct to standard WGCNA, results in better network partitions. These improved partitions enable more fruitful downstream analyses, as gene modules are more biologically meaningful.

  8. Sieve-based relation extraction of gene regulatory networks from biological literature. (United States)

    Žitnik, Slavko; Žitnik, Marinka; Zupan, Blaž; Bajec, Marko


    Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice of transforming

  9. 3-D components of a biological neural network visualized in computer generated imagery. II - Macular neural network organization (United States)

    Ross, Muriel D.; Meyer, Glenn; Lam, Tony; Cutler, Lynn; Vaziri, Parshaw


    Computer-assisted reconstructions of small parts of the macular neural network show how the nerve terminals and receptive fields are organized in 3-dimensional space. This biological neural network is anatomically organized for parallel distributed processing of information. Processing appears to be more complex than in computer-based neural network, because spatiotemporal factors figure into synaptic weighting. Serial reconstruction data show anatomical arrangements which suggest that (1) assemblies of cells analyze and distribute information with inbuilt redundancy, to improve reliability; (2) feedforward/feedback loops provide the capacity for presynaptic modulation of output during processing; (3) constrained randomness in connectivities contributes to adaptability; and (4) local variations in network complexity permit differing analyses of incoming signals to take place simultaneously. The last inference suggests that there may be segregation of information flow to central stations subserving particular functions.

  10. Tensor Fusion Network for Multimodal Sentiment Analysis


    Zadeh, Amir; Chen, Minghai; Poria, Soujanya; Cambria, Erik; Morency, Louis-Philippe


    Multimodal sentiment analysis is an increasingly popular research area, which extends the conventional language-based definition of sentiment analysis to a multimodal setup where other relevant modalities accompany language. In this paper, we pose the problem of multimodal sentiment analysis as modeling intra-modality and inter-modality dynamics. We introduce a novel model, termed Tensor Fusion Network, which learns both such dynamics end-to-end. The proposed approach is tailored for the vola...

  11. NAPS: Network Analysis of Protein Structures (United States)

    Chakrabarty, Broto; Parekh, Nita


    Traditionally, protein structures have been analysed by the secondary structure architecture and fold arrangement. An alternative approach that has shown promise is modelling proteins as a network of non-covalent interactions between amino acid residues. The network representation of proteins provide a systems approach to topological analysis of complex three-dimensional structures irrespective of secondary structure and fold type and provide insights into structure-function relationship. We have developed a web server for network based analysis of protein structures, NAPS, that facilitates quantitative and qualitative (visual) analysis of residue–residue interactions in: single chains, protein complex, modelled protein structures and trajectories (e.g. from molecular dynamics simulations). The user can specify atom type for network construction, distance range (in Å) and minimal amino acid separation along the sequence. NAPS provides users selection of node(s) and its neighbourhood based on centrality measures, physicochemical properties of amino acids or cluster of well-connected residues (k-cliques) for further analysis. Visual analysis of interacting domains and protein chains, and shortest path lengths between pair of residues are additional features that aid in functional analysis. NAPS support various analyses and visualization views for identifying functional residues, provide insight into mechanisms of protein folding, domain-domain and protein–protein interactions for understanding communication within and between proteins. URL: PMID:27151201

  12. Deep Neural Networks: A New Framework for Modeling Biological Vision and Brain Information Processing. (United States)

    Kriegeskorte, Nikolaus


    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.

  13. Information theory in systems biology. Part II: protein-protein interaction and signaling networks. (United States)

    Mousavian, Zaynab; Díaz, José; Masoudi-Nejad, Ali


    By the development of information theory in 1948 by Claude Shannon to address the problems in the field of data storage and data communication over (noisy) communication channel, it has been successfully applied in many other research areas such as bioinformatics and systems biology. In this manuscript, we attempt to review some of the existing literatures in systems biology, which are using the information theory measures in their calculations. As we have reviewed most of the existing information-theoretic methods in gene regulatory and metabolic networks in the first part of the review, so in the second part of our study, the application of information theory in other types of biological networks including protein-protein interaction and signaling networks will be surveyed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Automated Analysis of Security in Networking Systems

    DEFF Research Database (Denmark)

    Buchholtz, Mikael


    It has for a long time been a challenge to built secure networking systems. One way to counter this problem is to provide developers of software applications for networking systems with easy-to-use tools that can check security properties before the applications ever reach the marked. These tools...... will both help raise the general level of awareness of the problems and prevent the most basic flaws from occurring. This thesis contributes to the development of such tools. Networking systems typically try to attain secure communication by applying standard cryptographic techniques. In this thesis...... attacks, and attacks launched by insiders. Finally, the perspectives for the application of the analysis techniques are discussed, thereby, coming a small step closer to providing developers with easy- to-use tools for validating the security of networking applications....

  15. A statistical analysis of UK financial networks (United States)

    Chu, J.; Nadarajah, S.


    In recent years, with a growing interest in big or large datasets, there has been a rise in the application of large graphs and networks to financial big data. Much of this research has focused on the construction and analysis of the network structure of stock markets, based on the relationships between stock prices. Motivated by Boginski et al. (2005), who studied the characteristics of a network structure of the US stock market, we construct network graphs of the UK stock market using same method. We fit four distributions to the degree density of the vertices from these graphs, the Pareto I, Fréchet, lognormal, and generalised Pareto distributions, and assess the goodness of fit. Our results show that the degree density of the complements of the market graphs, constructed using a negative threshold value close to zero, can be fitted well with the Fréchet and lognormal distributions.

  16. Classification and Analysis of Computer Network Traffic

    DEFF Research Database (Denmark)

    Bujlow, Tomasz


    for traffic classification, which can be used for nearly real-time processing of big amounts of data using affordable CPU and memory resources. Other questions are related to methods for real-time estimation of the application Quality of Service (QoS) level based on the results obtained by the traffic...... to create realistic traffic profiles of the selected applications, which can server as the training data for MLAs. We assessed the usefulness of C5.0 Machine Learning Algorithm (MLA) in the classification of computer network traffic. We showed that the application-layer payload is not needed to train the C5......Traffic monitoring and analysis can be done for multiple different reasons: to investigate the usage of network resources, assess the performance of network applications, adjust Quality of Service (QoS) policies in the network, log the traffic to comply with the law, or create realistic models...

  17. Systems genomics analysis centered on epigenetic inheritance supports development of a unified theory of biology. (United States)

    Sharma, Abhay


    New discoveries are increasingly demanding integration of epigenetics, molecular biology, genomic networks and physiology with evolution. This article provides a proof of concept for evolutionary transgenerational systems biology, proposed recently in the context of epigenetic inheritance in mammals. Gene set enrichment analysis of available genome-level mammalian data presented here seem consistent with the concept that: (1) heritable information about environmental effects in somatic cells is communicated to the germline by circulating microRNAs (miRNAs) or other RNAs released in physiological fluids; (2) epigenetic factors including miRNA-like small RNAs, DNA methylation and histone modifications are propagated across generations via gene networks; and (3) inherited epigenetic variations in the form of methylated cytosines are fixed in the population as thymines over the evolutionary time course. The analysis supports integration of physiology and epigenetics with inheritance and evolution. This may catalyze efforts to develop a unified theory of biology. © 2015. Published by The Company of Biologists Ltd.

  18. Network Analysis: A Novel Approach to Understand Suicidal Behaviour

    Directory of Open Access Journals (Sweden)

    Derek de Beurs


    Full Text Available Although suicide is a major public health issue worldwide, we understand little of the onset and development of suicidal behaviour. Suicidal behaviour is argued to be the end result of the complex interaction between psychological, social and biological factors. Epidemiological studies resulted in a range of risk factors for suicidal behaviour, but we do not yet understand how their interaction increases the risk for suicidal behaviour. A new approach called network analysis can help us better understand this process as it allows us to visualize and quantify the complex association between many different symptoms or risk factors. A network analysis of data containing information on suicidal patients can help us understand how risk factors interact and how their interaction is related to suicidal thoughts and behaviour. A network perspective has been successfully applied to the field of depression and psychosis, but not yet to the field of suicidology. In this theoretical article, I will introduce the concept of network analysis to the field of suicide prevention, and offer directions for future applications and studies.

  19. Construction of biological networks from unstructured information based on a semi-automated curation workflow. (United States)

    Szostak, Justyna; Ansari, Sam; Madan, Sumit; Fluck, Juliane; Talikka, Marja; Iskandar, Anita; De Leon, Hector; Hofmann-Apitius, Martin; Peitsch, Manuel C; Hoeng, Julia


    Capture and representation of scientific knowledge in a structured format are essential to improve the understanding of biological mechanisms involved in complex diseases. Biological knowledge and knowledge about standardized terminologies are difficult to capture from literature in a usable form. A semi-automated knowledge extraction workflow is presented that was developed to allow users to extract causal and correlative relationships from scientific literature and to transcribe them into the computable and human readable Biological Expression Language (BEL). The workflow combines state-of-the-art linguistic tools for recognition of various entities and extraction of knowledge from literature sources. Unlike most other approaches, the workflow outputs the results to a curation interface for manual curation and converts them into BEL documents that can be compiled to form biological networks. We developed a new semi-automated knowledge extraction workflow that was designed to capture and organize scientific knowledge and reduce the required curation skills and effort for this task. The workflow was used to build a network that represents the cellular and molecular mechanisms implicated in atherosclerotic plaque destabilization in an apolipoprotein-E-deficient (ApoE(-/-)) mouse model. The network was generated using knowledge extracted from the primary literature. The resultant atherosclerotic plaque destabilization network contains 304 nodes and 743 edges supported by 33 PubMed referenced articles. A comparison between the semi-automated and conventional curation processes showed similar results, but significantly reduced curation effort for the semi-automated process. Creating structured knowledge from unstructured text is an important step for the mechanistic interpretation and reusability of knowledge. Our new semi-automated knowledge extraction workflow reduced the curation skills and effort required to capture and organize scientific knowledge. The

  20. Network Analysis of Rodent Transcriptomes in Spaceflight (United States)

    Ramachandran, Maya; Fogle, Homer; Costes, Sylvain


    Network analysis methods leverage prior knowledge of cellular systems and the statistical and conceptual relationships between analyte measurements to determine gene connectivity. Correlation and conditional metrics are used to infer a network topology and provide a systems-level context for cellular responses. Integration across multiple experimental conditions and omics domains can reveal the regulatory mechanisms that underlie gene expression. GeneLab has assembled rich multi-omic (transcriptomics, proteomics, epigenomics, and epitranscriptomics) datasets for multiple murine tissues from the Rodent Research 1 (RR-1) experiment. RR-1 assesses the impact of 37 days of spaceflight on gene expression across a variety of tissue types, such as adrenal glands, quadriceps, gastrocnemius, tibalius anterior, extensor digitorum longus, soleus, eye, and kidney. Network analysis is particularly useful for RR-1 -omics datasets because it reinforces subtle relationships that may be overlooked in isolated analyses and subdues confounding factors. Our objective is to use network analysis to determine potential target nodes for therapeutic intervention and identify similarities with existing disease models. Multiple network algorithms are used for a higher confidence consensus.

  1. The BIOSCI electronic newsgroup network for the biological sciences. Final report, October 1, 1992--June 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Kristofferson, D.; Mack, D.


    This is the final report for a DOE funded project on BIOSCI Electronic Newsgroup Network for the biological sciences. A usable network for scientific discussion, major announcements, problem solving, etc. has been created.

  2. Activation analysis of biological materials at the Activation Analysis Centre

    International Nuclear Information System (INIS)

    Kukula, F.; Obrusnik, I.; Simkova, M.; Kucera, J.; Krivanek, M.


    A review is presented of the work of the Activation Analysis Centre of the Nuclear Research Institute for different fields of the Czechoslovak economy, aimed primarily at analyzing biological materials with the purpose of determining the contents of the so-called vital trace elements and of elements which already have a toxic effect on the organism in trace concentrations. Another important field of research is the path of trace elements from the environment to the human organism. A destructive method for the simultaneous determination of 12 trace elements in 11 kinds of human tissue has been studied. (Z.M.)

  3. Phylodynamic analysis of a viral infection network

    Directory of Open Access Journals (Sweden)

    Teiichiro eShiino


    Full Text Available Viral infections by sexual and droplet transmission routes typically spread through a complex host-to-host contact network. Clarifying the transmission network and epidemiological parameters affecting the variations and dynamics of a specific pathogen is a major issue in the control of infectious diseases. However, conventional methods such as interview and/or classical phylogenetic analysis of viral gene sequences have inherent limitations and often fail to detect infectious clusters and transmission connections. Recent improvements in computational environments now permit the analysis of large datasets. In addition, novel analytical methods have been developed that serve to infer the evolutionary dynamics of virus genetic diversity using sample date information and sequence data. This type of framework, termed phylodynamics, helps connect some of the missing links on viral transmission networks, which are often hard to detect by conventional methods of epidemiology. With sufficient number of sequences available, one can use this new inference method to estimate theoretical epidemiological parameters such as temporal distributions of the primary infection, fluctuation of the pathogen population size, basic reproductive number, and the mean time span of disease infectiousness. Transmission networks estimated by this framework often have the properties of a scale-free network, which are characteristic of infectious and social communication processes. Network analysis based on phylodynamics has alluded to various suggestions concerning the infection dynamics associated with a given community and/or risk behavior. In this review, I will summarize the current methods available for identifying the transmission network using phylogeny, and present an argument on the possibilities of applying the scale-free properties to these existing frameworks.

  4. Analysis of undergraduate cell biology contents in Brazilian public universities. (United States)

    Mermelstein, Claudia; Costa, Manoel Luis


    The enormous amount of information available in cell biology has created a challenge in selecting the core concepts we should be teaching our undergraduates. One way to define a set of essential core ideas in cell biology is to analyze what a specific cell biology community is teaching their students. Our main objective was to analyze the cell biology content currently being taught in Brazilian universities. We collected the syllabi of cell biology courses from public universities in Brazil and analyzed the frequency of cell biology topics in each course. We also compared the Brazilian data with the contents of a major cell biology textbook. Our analysis showed that while some cell biology topics such as plasma membrane and cytoskeleton was present in ∼100% of the Brazilian curricula analyzed others such as cell signaling and cell differentiation were present in only ∼35%. The average cell biology content taught in the Brazilian universities is quite different from what is presented in the textbook. We discuss several possible explanations for these observations. We also suggest a list with essential cell biology topics for any biological or biomedical undergraduate course. The comparative discussion of cell biology topics presented here could be valuable in other educational contexts. © 2017 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

  5. A systems biology model of the regulatory network in Populus leaves reveals interacting regulators and conserved regulation

    Directory of Open Access Journals (Sweden)

    Hvidsten Torgeir R


    Full Text Available Abstract Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species. Results We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis. Conclusions We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions

  6. Stochastic noncooperative and cooperative evolutionary game strategies of a population of biological networks under natural selection. (United States)

    Chen, Bor-Sen; Yeh, Chin-Hsun


    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.

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

    KAUST Repository

    Alanis Lobato, Gregorio


    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.

  8. Bandwidth Analysis of Smart Meter Network Infrastructure

    DEFF Research Database (Denmark)

    Balachandran, Kardi; Olsen, Rasmus Løvenstein; Pedersen, Jens Myrup


    Advanced Metering Infrastructure (AMI) is a net-work infrastructure in Smart Grid, which links the electricity customers to the utility company. This network enables smart services by making it possible for the utility company to get an overview of their customers power consumption and also control...... to utilize smart meters and which existing broadband network technologies can facilitate this smart meter service. Initially, scenarios for smart meter infrastructure are identified. The paper defines abstraction models which cover the AMI scenarios. When the scenario has been identified a general overview...... of the bandwidth requirements are analysed. For this analysis the assumptions and limitations are defined. The results obtained by the analysis show, that the amount of data collected and transferred by a smart meter is very low compared to the available bandwidth of most internet connections. The results show...

  9. Multifractal analysis of mobile social networks (United States)

    Zheng, Wei; Zhang, Zifeng; Deng, Yufan


    As Wireless Fidelity (Wi-Fi)-enabled handheld devices have been widely used, the mobile social networks (MSNs) has been attracting extensive attention. Fractal approaches have also been widely applied to characterierize natural networks as useful tools to depict their spatial distribution and scaling properties. Moreover, when the complexity of the spatial distribution of MSNs cannot be properly charaterized by single fractal dimension, multifractal analysis is required. For further research, we introduced a multifractal analysis method based on box-covering algorithm to describe the structure of MSNs. Using this method, we find that the networks are multifractal at different time interval. The simulation results demonstrate that the proposed method is efficient for analyzing the multifractal characteristic of MSNs, which provides a distribution of singularities adequately describing both the heterogeneity of fractal patterns and the statistics of measurements across spatial scales in MSNs.

  10. Vulnerability analysis methods for road networks (United States)

    Bíl, Michal; Vodák, Rostislav; Kubeček, Jan; Rebok, Tomáš; Svoboda, Tomáš


    Road networks rank among the most important lifelines of modern society. They can be damaged by either random or intentional events. Roads are also often affected by natural hazards, the impacts of which are both direct and indirect. Whereas direct impacts (e.g. roads damaged by a landslide or due to flooding) are localized in close proximity to the natural hazard occurrence, the indirect impacts can entail widespread service disabilities and considerable travel delays. The change in flows in the network may affect the population living far from the places originally impacted by the natural disaster. These effects are primarily possible due to the intrinsic nature of this system. The consequences and extent of the indirect costs also depend on the set of road links which were damaged, because the road links differ in terms of their importance. The more robust (interconnected) the road network is, the less time is usually needed to secure the serviceability of an area hit by a disaster. These kinds of networks also demonstrate a higher degree of resilience. Evaluating road network structures is therefore essential in any type of vulnerability and resilience analysis. There are a range of approaches used for evaluation of the vulnerability of a network and for identification of the weakest road links. Only few of them are, however, capable of simulating the impacts of the simultaneous closure of numerous links, which often occurs during a disaster. The primary problem is that in the case of a disaster, which usually has a large regional extent, the road network may remain disconnected. The majority of the commonly used indices use direct computation of the shortest paths or time between OD (origin - destination) pairs and therefore cannot be applied when the network breaks up into two or more components. Since extensive break-ups often occur in cases of major disasters, it is important to study the network vulnerability in these cases as well, so that appropriate

  11. Diversity Performance Analysis on Multiple HAP Networks

    Directory of Open Access Journals (Sweden)

    Feihong Dong


    Full Text Available One of the main design challenges in wireless sensor networks (WSNs is achieving a high-data-rate transmission for individual sensor devices. The high altitude platform (HAP is an important communication relay platform for WSNs and next-generation wireless networks. Multiple-input multiple-output (MIMO techniques provide the diversity and multiplexing gain, which can improve the network performance effectively. In this paper, a virtual MIMO (V-MIMO model is proposed by networking multiple HAPs with the concept of multiple assets in view (MAV. In a shadowed Rician fading channel, the diversity performance is investigated. The probability density function (PDF and cumulative distribution function (CDF of the received signal-to-noise ratio (SNR are derived. In addition, the average symbol error rate (ASER with BPSK and QPSK is given for the V-MIMO model. The system capacity is studied for both perfect channel state information (CSI and unknown CSI individually. The ergodic capacity with various SNR and Rician factors for different network configurations is also analyzed. The simulation results validate the effectiveness of the performance analysis. It is shown that the performance of the HAPs network in WSNs can be significantly improved by utilizing the MAV to achieve overlapping coverage, with the help of the V-MIMO techniques.

  12. Combining morphological analysis and Bayesian networks for ...

    African Journals Online (AJOL)

    ... how these two computer aided methods may be combined to better facilitate modelling procedures. A simple example is presented, concerning a recent application in the field of environmental decision support. Keywords: Morphological analysis, Bayesian networks, strategic decision support. ORiON Vol. 23 (2) 2007: pp.

  13. Ecological network analysis of China's societal metabolism. (United States)

    Zhang, Yan; Liu, Hong; Li, Yating; Yang, Zhifeng; Li, Shengsheng; Yang, Naijin


    Uncontrolled socioeconomic development has strong negative effects on the ecological environment, including pollution and the depletion and waste of natural resources. These serious consequences result from the high flows of materials and energy through a socioeconomic system produced by exchanges between the system and its surroundings, causing the disturbance of metabolic processes. In this paper, we developed an ecological network model for a societal system, and used China in 2006 as a case study to illustrate application of the model. We analyzed China's basic metabolic processes and used ecological network analysis to study the network relationships within the system. Basic components comprised the internal environment, five sectors (agriculture, exploitation, manufacturing, domestic, and recycling), and the external environment. We defined 21 pairs of ecological relationships in China's societal metabolic system (excluding self-mutualism within a component). Using utility and throughflow analysis, we found that exploitation, mutualism, and competition relationships accounted for 76.2, 14.3, and 9.5% of the total relationships, respectively. In our trophic level analysis, the components were divided into producers, consumers, and decomposers according to their positions in the system. Our analyses revealed ways to optimize the system's structure and adjust its functions, thereby promoting healthier socioeconomic development, and suggested ways to apply ecological network analysis in future socioeconomic research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Nonlinear Time Series Analysis via Neural Networks (United States)

    Volná, Eva; Janošek, Michal; Kocian, Václav; Kotyrba, Martin

    This article deals with a time series analysis based on neural networks in order to make an effective forex market [Moore and Roche, J. Int. Econ. 58, 387-411 (2002)] pattern recognition. Our goal is to find and recognize important patterns which repeatedly appear in the market history to adapt our trading system behaviour based on them.

  15. A biologically inspired neural network controller for ballistic arm movements

    Directory of Open Access Journals (Sweden)

    Schmid Maurizio


    Full Text Available Abstract Background In humans, the implementation of multijoint tasks of the arm implies a highly complex integration of sensory information, sensorimotor transformations and motor planning. Computational models can be profitably used to better understand the mechanisms sub-serving motor control, thus providing useful perspectives and investigating different control hypotheses. To this purpose, the use of Artificial Neural Networks has been proposed to represent and interpret the movement of upper limb. In this paper, a neural network approach to the modelling of the motor control of a human arm during planar ballistic movements is presented. Methods The developed system is composed of three main computational blocks: 1 a parallel distributed learning scheme that aims at simulating the internal inverse model in the trajectory formation process; 2 a pulse generator, which is responsible for the creation of muscular synergies; and 3 a limb model based on two joints (two degrees of freedom and six muscle-like actuators, that can accommodate for the biomechanical parameters of the arm. The learning paradigm of the neural controller is based on a pure exploration of the working space with no feedback signal. Kinematics provided by the system have been compared with those obtained in literature from experimental data of humans. Results The model reproduces kinematics of arm movements, with bell-shaped wrist velocity profiles and approximately straight trajectories, and gives rise to the generation of synergies for the execution of movements. The model allows achieving amplitude and direction errors of respectively 0.52 cm and 0.2 radians. Curvature values are similar to those encountered in experimental measures with humans. The neural controller also manages environmental modifications such as the insertion of different force fields acting on the end-effector. Conclusion The proposed system has been shown to properly simulate the development of

  16. Incorporating network structure in integrative analysis of cancer prognosis data. (United States)

    Liu, Jin; Huang, Jian; Ma, Shuangge


    In high-throughput cancer genomic studies, markers identified from the analysis of single datasets may have unsatisfactory properties because of low sample sizes. Integrative analysis pools and analyzes raw data from multiple studies, and can effectively increase sample size and lead to improved marker identification results. In this study, we consider the integrative analysis of multiple high-throughput cancer prognosis studies. In the existing integrative analysis studies, the interplay among genes, which can be described using the network structure, has not been effectively accounted for. In network analysis, tightly connected nodes (genes) are more likely to have related biological functions and similar regression coefficients. The goal of this study is to develop an analysis approach that can incorporate the gene network structure in integrative analysis. To this end, we adopt an AFT (accelerated failure time) model to describe survival. A weighted least squares approach, which has low computational cost, is adopted for estimation. For marker selection, we propose a new penalization approach. The proposed penalty is composed of two parts. The first part is a group MCP penalty, and conducts gene selection. The second part is a Laplacian penalty, and smoothes the differences of coefficients for tightly connected genes. A group coordinate descent approach is developed to compute the proposed estimate. Simulation study shows satisfactory performance of the proposed approach when there exist moderate-to-strong correlations among genes. We analyze three lung cancer prognosis datasets, and demonstrate that incorporating the network structure can lead to the identification of important genes and improved prediction performance. © 2012 WILEY PERIODICALS, INC.

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

    Directory of Open Access Journals (Sweden)

    Jacob Beal

    Full Text Available 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. Time series analysis of temporal networks (United States)

    Sikdar, Sandipan; Ganguly, Niloy; Mukherjee, Animesh


    A common but an important feature of all real-world networks is that they are temporal in nature, i.e., the network structure changes over time. Due to this dynamic nature, it becomes difficult to propose suitable growth models that can explain the various important characteristic properties of these networks. In fact, in many application oriented studies only knowing these properties is sufficient. For instance, if one wishes to launch a targeted attack on a network, this can be done even without the knowledge of the full network structure; rather an estimate of some of the properties is sufficient enough to launch the attack. We, in this paper show that even if the network structure at a future time point is not available one can still manage to estimate its properties. We propose a novel method to map a temporal network to a set of time series instances, analyze them and using a standard forecast model of time series, try to predict the properties of a temporal network at a later time instance. To our aim, we consider eight properties such as number of active nodes, average degree, clustering coefficient etc. and apply our prediction framework on them. We mainly focus on the temporal network of human face-to-face contacts and observe that it represents a stochastic process with memory that can be modeled as Auto-Regressive-Integrated-Moving-Average (ARIMA). We use cross validation techniques to find the percentage accuracy of our predictions. An important observation is that the frequency domain properties of the time series obtained from spectrogram analysis could be used to refine the prediction framework by identifying beforehand the cases where the error in prediction is likely to be high. This leads to an improvement of 7.96% (for error level ≤20%) in prediction accuracy on an average across all datasets. As an application we show how such prediction scheme can be used to launch targeted attacks on temporal networks. Contribution to the Topical Issue

  19. Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections (United States)

    Lipner, Ettie M.; Garcia, Benjamin J.; Strong, Michael


    Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects. PMID:26751573

  20. Instrumental neutron activation analysis of biological samples

    International Nuclear Information System (INIS)

    Guinn, V.P.; Gavrilas, M.


    The elemental compositions of 18 biological reference materials have been processed, for 14 stepped combinations of irradiation/decay/counting times, by the INAA Advance Prediction Computer Program. The 18 materials studied include 11 plant materials, 5 animal materials, and 2 other biological materials. Of these 18 materials, 14 are NBS Standard Reference Materials and four are IAEA reference materials. Overall, the results show that a mean of 52% of the input elements can be determined to a relative standard deviation of ±10% or better by reactor flux (thermal plus epithermal) INAA

  1. Data acquisition and analysis at the Structural Biology Center

    International Nuclear Information System (INIS)

    Westbrook, M.L.; Coleman, T.A.; Daly, R.T.; Pflugrath, J.W.


    The Structural Biology Center (SBC), a national user facility for macromolecular crystallography located at Argonne National Laboratory's Advanced Photon Source, is currently being built and commissioned. SBC facilities include a bending-magnet beamline, an insertion-device beamline, laboratory and office space adjacent to the beamlines, and associated instrumentation, experimental apparatus, and facilities. SBC technical facilities will support anomalous dispersion phasing experiments, data collection from microcrystals, data collection from crystals with large molecular structures and rapid data collection from multiple related crystal structures for protein engineering and drug design. The SBC Computing Systems and Software Engineering Group is tasked with developing the SBC Control System, which includes computing systems, network, and software. The emphasis of SBC Control System development has been to provide efficient and convenient beamline control, data acquisition, and data analysis for maximal facility and experimenter productivity. This paper describes the SBC Control System development, specifically data acquisition and analysis at the SBC, and the development methods used to meet this goal

  2. Discriminating Different Classes of Biological Networks by Analyzing the Graphs Spectra Distribution (United States)

    Takahashi, Daniel Yasumasa; Sato, João Ricardo; Ferreira, Carlos Eduardo; Fujita, André


    The brain's structural and functional systems, protein-protein interaction, and gene networks are examples of biological systems that share some features of complex networks, such as highly connected nodes, modularity, and small-world topology. Recent studies indicate that some pathologies present topological network alterations relative to norms seen in the general population. Therefore, methods to discriminate the processes that generate the different classes of networks (e.g., normal and disease) might be crucial for the diagnosis, prognosis, and treatment of the disease. It is known that several topological properties of a network (graph) can be described by the distribution of the spectrum of its adjacency matrix. Moreover, large networks generated by the same random process have the same spectrum distribution, allowing us to use it as a “fingerprint”. Based on this relationship, we introduce and propose the entropy of a graph spectrum to measure the “uncertainty” of a random graph and the Kullback-Leibler and Jensen-Shannon divergences between graph spectra to compare networks. We also introduce general methods for model selection and network model parameter estimation, as well as a statistical procedure to test the nullity of divergence between two classes of complex networks. Finally, we demonstrate the usefulness of the proposed methods by applying them to (1) protein-protein interaction networks of different species and (2) on networks derived from children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) and typically developing children. We conclude that scale-free networks best describe all the protein-protein interactions. Also, we show that our proposed measures succeeded in the identification of topological changes in the network while other commonly used measures (number of edges, clustering coefficient, average path length) failed. PMID:23284629

  3. Capacity analysis of wireless mesh networks | Gumel | Nigerian ...

    African Journals Online (AJOL)

    ... number of nodes (n) in a linear topology. The degradation is found to be higher in a fully mesh network as a result of increase in interference and MAC layer contention in the network. Key words: Wireless mesh network (WMN), Adhoc network, Network capacity analysis, Bottleneck collision domain, Medium access control ...

  4. Capacity analysis of vehicular communication networks

    CERN Document Server

    Lu, Ning


    This SpringerBrief focuses on the network capacity analysis of VANETs, a key topic as fundamental guidance on design and deployment of VANETs is very limited. Moreover, unique characteristics of VANETs impose distinguished challenges on such an investigation. This SpringerBrief first introduces capacity scaling laws for wireless networks and briefly reviews the prior arts in deriving the capacity of VANETs. It then studies the unicast capacity considering the socialized mobility model of VANETs. With vehicles communicating based on a two-hop relaying scheme, the unicast capacity bound is deriv

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

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


    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. What do interaction network metrics tell us about specialization and biological traits? (United States)

    Blüthgen, Nico; Fründ, Jochen; Vázquez, Diego P; Menzel, Florian


    The structure of ecological interaction networks is often interpreted as a product of meaningful ecological and evolutionary mechanisms that shape the degree of specialization in community associations. However, here we show that both unweighted network metrics (connectance, nestedness, and degree distribution) and weighted network metrics (interaction evenness, interaction strength asymmetry) are strongly constrained and biased by the number of observations. Rarely observed species are inevitably regarded as "specialists," irrespective of their actual associations, leading to biased estimates of specialization. Consequently, a skewed distribution of species observation records (such as the lognormal), combined with a relatively low sampling density typical for ecological data, already generates a "nested" and poorly "connected" network with "asymmetric interaction strengths" when interactions are neutral. This is confirmed by null model simulations of bipartite networks, assuming that partners associate randomly in the absence of any specialization and any variation in the correspondence of biological traits between associated species (trait matching). Variation in the skewness of the frequency distribution fundamentally changes the outcome of network metrics. Therefore, interpretation of network metrics in terms of fundamental specialization and trait matching requires an appropriate control for such severe constraints imposed by information deficits. When using an alternative approach that controls for these effects, most natural networks of mutualistic or antagonistic systems show a significantly higher degree of reciprocal specialization (exclusiveness) than expected under neutral conditions. A higher exclusiveness is coherent with a tighter coevolution and suggests a lower ecological redundancy than implied by nested networks.

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


    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

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

    Directory of Open Access Journals (Sweden)

    Victor Trevino


    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

  9. Economic Analysis of Biological Invasions in Forests (United States)

    Tomas P. Holmes; Julian Aukema; Jeffrey Englin; Robert G. Haight; Kent Kovacs; Brian Leung


    Biological invasions of native forests by nonnative pests result from complex stochastic processes that are difficult to predict. Although economic optimization models describe efficient controls across the stages of an invasion, the ability to calibrate such models is constrained by lack of information on pest population dynamics and consequent economic damages. Here...

  10. A robust and biologically plausible spike pattern recognition network. (United States)

    Larson, Eric; Perrone, Ben P; Sen, Kamal; Billimoria, Cyrus P


    The neural mechanisms that enable recognition of spiking patterns in the brain are currently unknown. This is especially relevant in sensory systems, in which the brain has to detect such patterns and recognize relevant stimuli by processing peripheral inputs; in particular, it is unclear how sensory systems can recognize time-varying stimuli by processing spiking activity. Because auditory stimuli are represented by time-varying fluctuations in frequency content, it is useful to consider how such stimuli can be recognized by neural processing. Previous models for sound recognition have used preprocessed or low-level auditory signals as input, but complex natural sounds such as speech are thought to be processed in auditory cortex, and brain regions involved in object recognition in general must deal with the natural variability present in spike trains. Thus, we used neural recordings to investigate how a spike pattern recognition system could deal with the intrinsic variability and diverse response properties of cortical spike trains. We propose a biologically plausible computational spike pattern recognition model that uses an excitatory chain of neurons to spatially preserve the temporal representation of the spike pattern. Using a single neural recording as input, the model can be trained using a spike-timing-dependent plasticity-based learning rule to recognize neural responses to 20 different bird songs with >98% accuracy and can be stimulated to evoke reverse spike pattern playback. Although we test spike train recognition performance in an auditory task, this model can be applied to recognize sufficiently reliable spike patterns from any neuronal system.

  11. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research

    Directory of Open Access Journals (Sweden)

    Junyi Li


    Full Text Available With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA based on gene coexpression network (GCN increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.

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

    Indian Academy of Sciences (India)

    malignancy. [Wang J and Sen S 2011 MicroRNA functional network in pancreatic cancer: From biology to biomarkers of disease. J. Biosci. 36 481–491] ... aid in improving clinical management and therapeutic outcome for the patients. ..... 133a is a characteristic of pancreatic tissue and that a total of. 26 miRs are aberrantly ...


    Directory of Open Access Journals (Sweden)



    Full Text Available Altogether 327 valleys and their 314 cross-sectional profiles were analyzed on Mars, including width, depth, length, eroded volume, drainage and spatial density, as well as the network structure.According to this systematic analysis, five possible drainage network types were identified such as (a small valleys, (b integrated small valleys, (c individual, medium-sized valleys, (d unconfined,anastomosing outflow valleys, and (e confined outflow valleys. Measuring their various morphometric parameters, these five networks differ from each other in terms of parameters of the eroded volume, drainage density and depth values. This classification is more detailed than those described in the literature previously and correlated to several numerical parameters for the first time.These different types were probably formed during different periods of the evolution of Mars, and sprung from differently localized water sources, and they could be correlated to similar fluvialnetwork types from the Earth.

  14. Intentional risk management through complex networks analysis

    CERN Document Server

    Chapela, Victor; Moral, Santiago; Romance, Miguel


    This book combines game theory and complex networks to examine intentional technological risk through modeling. As information security risks are in constant evolution,  the methodologies and tools to manage them must evolve to an ever-changing environment. A formal global methodology is explained  in this book, which is able to analyze risks in cyber security based on complex network models and ideas extracted from the Nash equilibrium. A risk management methodology for IT critical infrastructures is introduced which provides guidance and analysis on decision making models and real situations. This model manages the risk of succumbing to a digital attack and assesses an attack from the following three variables: income obtained, expense needed to carry out an attack, and the potential consequences for an attack. Graduate students and researchers interested in cyber security, complex network applications and intentional risk will find this book useful as it is filled with a number of models, methodologies a...

  15. Mathematical Analysis of Urban Spatial Networks

    CERN Document Server

    Blanchard, Philippe


    Cities can be considered to be among the largest and most complex artificial networks created by human beings. Due to the numerous and diverse human-driven activities, urban network topology and dynamics can differ quite substantially from that of natural networks and so call for an alternative method of analysis. The intent of the present monograph is to lay down the theoretical foundations for studying the topology of compact urban patterns, using methods from spectral graph theory and statistical physics. These methods are demonstrated as tools to investigate the structure of a number of real cities with widely differing properties: medieval German cities, the webs of city canals in Amsterdam and Venice, and a modern urban structure such as found in Manhattan. Last but not least, the book concludes by providing a brief overview of possible applications that will eventually lead to a useful body of knowledge for architects, urban planners and civil engineers.

  16. Biological network extraction from scientific literature: state of the art and challenges. (United States)

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


    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:

  17. Micro-macro analysis of complex networks. (United States)

    Marchiori, Massimo; Possamai, Lino


    Complex systems have attracted considerable interest because of their wide range of applications, and are often studied via a "classic" approach: study a specific system, find a complex network behind it, and analyze the corresponding properties. This simple methodology has produced a great deal of interesting results, but relies on an often implicit underlying assumption: the level of detail on which the system is observed. However, in many situations, physical or abstract, the level of detail can be one out of many, and might also depend on intrinsic limitations in viewing the data with a different level of abstraction or precision. So, a fundamental question arises: do properties of a network depend on its level of observability, or are they invariant? If there is a dependence, then an apparently correct network modeling could in fact just be a bad approximation of the true behavior of a complex system. In order to answer this question, we propose a novel micro-macro analysis of complex systems that quantitatively describes how the structure of complex networks varies as a function of the detail level. To this extent, we have developed a new telescopic algorithm that abstracts from the local properties of a system and reconstructs the original structure according to a fuzziness level. This way we can study what happens when passing from a fine level of detail ("micro") to a different scale level ("macro"), and analyze the corresponding behavior in this transition, obtaining a deeper spectrum analysis. The obtained results show that many important properties are not universally invariant with respect to the level of detail, but instead strongly depend on the specific level on which a network is observed. Therefore, caution should be taken in every situation where a complex network is considered, if its context allows for different levels of observability.

  18. Constraints of Biological Neural Networks and Their Consideration in AI Applications

    Directory of Open Access Journals (Sweden)

    Richard Stafford


    Full Text Available Biological organisms do not evolve to perfection, but to out compete others in their ecological niche, and therefore survive and reproduce. This paper reviews the constraints imposed on imperfect organisms, particularly on their neural systems and ability to capture and process information accurately. By understanding biological constraints of the physical properties of neurons, simpler and more efficient artificial neural networks can be made (e.g., spiking networks will transmit less information than graded potential networks, spikes only occur in nature due to limitations of carrying electrical charges over large distances. Furthermore, understanding the behavioural and ecological constraints on animals allows an understanding of the limitations of bio-inspired solutions, but also an understanding of why bio-inspired solutions may fail and how to correct these failures.

  19. Complexity, Analysis and Control of Singular Biological Systems

    CERN Document Server

    Zhang, Qingling; Zhang, Xue


    Complexity, Analysis and Control of Singular Biological Systems follows the control of real-world biological systems at both ecological and phyisological levels concentrating on the application of now-extensively-investigated singular system theory. Much effort has recently been dedicated to the modelling and analysis of developing bioeconomic systems and the text establishes singular examples of these, showing how proper control can help to maintain sustainable economic development of biological resources. The book begins from the essentials of singular systems theory and bifurcations before tackling  the use of various forms of control in singular biological systems using examples including predator-prey relationships and viral vaccination and quarantine control. Researchers and graduate students studying the control of complex biological systems are shown how a variety of methods can be brought to bear and practitioners working with the economics of biological systems and their control will also find the ...

  20. Systems analysis of gene ontology and biological pathways involved in post-myocardial infarction responses. (United States)

    Nguyen, Nguyen T; Lindsey, Merry L; Jin, Yu-Fang


    Pathway analysis has been widely used to gain insight into essential mechanisms of the response to myocardial infarction (MI). Currently, there exist multiple pathway databases that organize molecular datasets and manually curate pathway maps for biological interpretation at varying forms of organization. However, inconsistencies among different databases in pathway descriptions, frequently due to conflicting results in the literature, can generate incorrect interpretations. Furthermore, although pathway analysis software provides detailed images of interactions among molecules, it does not exhibit how pathways interact with one another or with other biological processes under specific conditions. We propose a novel method to standardize descriptions of enriched pathways for a set of genes/proteins using Gene Ontology terms. We used this method to examine the relationships among pathways and biological processes for a set of condition-specific genes/proteins, represented as a functional biological pathway-process network. We applied this algorithm to a set of 613 MI-specific proteins we previously identified. A total of 96 pathways from Biocarta, KEGG, and Reactome, and 448 Gene Ontology Biological Processes were enriched with these 613 proteins. The pathways were represented as Boolean functions of biological processes, delivering an interactive scheme to organize enriched information with an emphasis on involvement of biological processes in pathways. We extracted a network focusing on MI to demonstrate that tyrosine phosphorylation of Signal Transducer and Activator of Transcription (STAT) protein, positive regulation of collagen metabolic process, coagulation, and positive/negative regulation of blood coagulation have immediate impacts on the MI response. Our method organized biological processes and pathways in an unbiased approach to provide an intuitive way to identify biological properties of pathways under specific conditions. Pathways from different

  1. Safeguards Network Analysis Procedure (SNAP): overview

    International Nuclear Information System (INIS)

    Chapman, L.D; Engi, D.


    Nuclear safeguards systems provide physical protection and control of nuclear materials. The Safeguards Network Analysis Procedure (SNAP) provides a convenient and standard analysis methodology for the evaluation of physical protection system effectiveness. This is achieved through a standard set of symbols which characterize the various elements of safeguards systems and an analysis program to execute simulation models built using the SNAP symbology. The outputs provided by the SNAP simulation program supplements the safeguards analyst's evaluative capabilities and supports the evaluation of existing sites as well as alternative design possibilities. This paper describes the SNAP modeling technique and provides an example illustrating its use

  2. MODA: an efficient algorithm for network motif discovery in biological networks. (United States)

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


    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:

  3. Principal component analysis networks and algorithms

    CERN Document Server

    Kong, Xiangyu; Duan, Zhansheng


    This book not only provides a comprehensive introduction to neural-based PCA methods in control science, but also presents many novel PCA algorithms and their extensions and generalizations, e.g., dual purpose, coupled PCA, GED, neural based SVD algorithms, etc. It also discusses in detail various analysis methods for the convergence, stabilizing, self-stabilizing property of algorithms, and introduces the deterministic discrete-time systems method to analyze the convergence of PCA/MCA algorithms. Readers should be familiar with numerical analysis and the fundamentals of statistics, such as the basics of least squares and stochastic algorithms. Although it focuses on neural networks, the book only presents their learning law, which is simply an iterative algorithm. Therefore, no a priori knowledge of neural networks is required. This book will be of interest and serve as a reference source to researchers and students in applied mathematics, statistics, engineering, and other related fields.

  4. A comparative analysis of South African Life Sciences and Biology ...

    African Journals Online (AJOL)

    This study reports on the analysis of South African Life Sciences and Biology textbooks for the inclusion of the nature of science using a conceptual framework developed by Chiappetta, Fillman and Sethna (1991). In particular, we investigated the differences between the representation of the nature of science in Biology ...

  5. Service network analysis for agricultural mental health

    Directory of Open Access Journals (Sweden)

    Fuller Jeffrey D


    Full Text Available Abstract Background Farmers represent a subgroup of rural and remote communities at higher risk of suicide attributed to insecure economic futures, self-reliant cultures and poor access to health services. Early intervention models are required that tap into existing farming networks. This study describes service networks in rural shires that relate to the mental health needs of farming families. This serves as a baseline to inform service network improvements. Methods A network survey of mental health related links between agricultural support, health and other human services in four drought declared shires in comparable districts in rural New South Wales, Australia. Mental health links covered information exchange, referral recommendations and program development. Results 87 agencies from 111 (78% completed a survey. 79% indicated that two thirds of their clients needed assistance for mental health related problems. The highest mean number of interagency links concerned information exchange and the frequency of these links between sectors was monthly to three monthly. The effectiveness of agricultural support and health sector links were rated as less effective by the agricultural support sector than by the health sector (p Conclusion Aligning with agricultural agencies is important to build effective mental health service pathways to address the needs of farming populations. Work is required to ensure that these agricultural support agencies have operational and effective links to primary mental health care services. Network analysis provides a baseline to inform this work. With interventions such as local mental health training and joint service planning to promote network development we would expect to see over time an increase in the mean number of links, the frequency in which these links are used and the rated effectiveness of these links.

  6. A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining

    Directory of Open Access Journals (Sweden)

    Lan Chung-Yu


    Full Text Available Abstract Background Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease. However, it is difficult to recognize and evaluate relevant biological processes from the huge quantities of experimental data. It is hence appealing to find an algorithm which can generate a gene regulatory network of systemic inflammation from high-throughput genomic studies of human diseases. Such network will be essential for us to extract valuable information from the complex and chaotic network under diseased conditions. Results In this study, we construct a gene regulatory network of inflammation using data extracted from the Ensembl and JASPAR databases. We also integrate and apply a number of systematic algorithms like cross correlation threshold, maximum likelihood estimation method and Akaike Information Criterion (AIC on time-lapsed microarray data to refine the genome-wide transcriptional regulatory network in response to bacterial endotoxins in the context of dynamic activated genes, which are regulated by transcription factors (TFs such as NF-κB. This systematic approach is used to investigate the stochastic interaction represented by the dynamic leukocyte gene expression profiles of human subject exposed to an inflammatory stimulus (bacterial endotoxin. Based on the kinetic parameters of the dynamic gene regulatory network, we identify important properties (such as susceptibility to infection of the immune system, which may be useful for translational research. Finally, robustness of the inflammatory gene network is also inferred by analyzing the hubs and "weak ties" structures of the gene network

  7. A user’s guide to network analysis in R

    CERN Document Server

    Luke, Douglas


    Presenting a comprehensive resource for the mastery of network analysis in R, the goal of Network Analysis with R is to introduce modern network analysis techniques in R to social, physical, and health scientists. The mathematical foundations of network analysis are emphasized in an accessible way and readers are guided through the basic steps of network studies: network conceptualization, data collection and management, network description, visualization, and building and testing statistical models of networks. As with all of the books in the Use R! series, each chapter contains extensive R code and detailed visualizations of datasets. Appendices will describe the R network packages and the datasets used in the book. An R package developed specifically for the book, available to readers on GitHub, contains relevant code and real-world network datasets as well.

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

    Directory of Open Access Journals (Sweden)

    Xin Lai


    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.

  9. A data integration approach for cell cycle analysis oriented to model simulation in systems biology

    Directory of Open Access Journals (Sweden)

    Mosca Ettore


    Full Text Available Abstract Background The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies. Description In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process. Conclusion This integrated system is freely available in order to support systems biology research on the cell cycle and

  10. Analytical framework for recurrence network analysis of time series. (United States)

    Donges, Jonathan F; Heitzig, Jobst; Donner, Reik V; Kurths, Jürgen


    Recurrence networks are a powerful nonlinear tool for time series analysis of complex dynamical systems. While there are already many successful applications ranging from medicine to paleoclimatology, a solid theoretical foundation of the method has still been missing so far. Here, we interpret an ɛ-recurrence network as a discrete subnetwork of a "continuous" graph with uncountably many vertices and edges corresponding to the system's attractor. This step allows us to show that various statistical measures commonly used in complex network analysis can be seen as discrete estimators of newly defined continuous measures of certain complex geometric properties of the attractor on the scale given by ɛ. In particular, we introduce local measures such as the ɛ-clustering coefficient, mesoscopic measures such as ɛ-motif density, path-based measures such as ɛ-betweennesses, and global measures such as ɛ-efficiency. This new analytical basis for the so far heuristically motivated network measures also provides an objective criterion for the choice of ɛ via a percolation threshold, and it shows that estimation can be improved by so-called node splitting invariant versions of the measures. We finally illustrate the framework for a number of archetypical chaotic attractors such as those of the Bernoulli and logistic maps, periodic and two-dimensional quasiperiodic motions, and for hyperballs and hypercubes by deriving analytical expressions for the novel measures and comparing them with data from numerical experiments. More generally, the theoretical framework put forward in this work describes random geometric graphs and other networks with spatial constraints, which appear frequently in disciplines ranging from biology to climate science.

  11. MONGKIE: an integrated tool for network analysis and visualization for multi-omics data. (United States)

    Jang, Yeongjun; Yu, Namhee; Seo, Jihae; Kim, Sun; Lee, Sanghyuk


    Network-based integrative analysis is a powerful technique for extracting biological insights from multilayered omics data such as somatic mutations, copy number variations, and gene expression data. However, integrated analysis of multi-omics data is quite complicated and can hardly be done in an automated way. Thus, a powerful interactive visual mining tool supporting diverse analysis algorithms for identification of driver genes and regulatory modules is much needed. Here, we present a software platform that integrates network visualization with omics data analysis tools seamlessly. The visualization unit supports various options for displaying multi-omics data as well as unique network models for describing sophisticated biological networks such as complex biomolecular reactions. In addition, we implemented diverse in-house algorithms for network analysis including network clustering and over-representation analysis. Novel functions include facile definition and optimized visualization of subgroups, comparison of a series of data sets in an identical network by data-to-visual mapping and subsequent overlaying function, and management of custom interaction networks. Utility of MONGKIE for network-based visual data mining of multi-omics data was demonstrated by analysis of the TCGA glioblastoma data. MONGKIE was developed in Java based on the NetBeans plugin architecture, thus being OS-independent with intrinsic support of module extension by third-party developers. We believe that MONGKIE would be a valuable addition to network analysis software by supporting many unique features and visualization options, especially for analysing multi-omics data sets in cancer and other diseases. .

  12. Northern emporia and maritime networks. Modelling past communication using archaeological network analysis

    DEFF Research Database (Denmark)

    Sindbæk, Søren Michael


    this is not a problem of network analysis, but network synthesis: theclassic problem of cracking codes or reconstructing black-box circuits. It is proposedthat archaeological approaches to network synthesis must involve a contextualreading of network data: observations arising from individual contexts, morphologies...

  13. NIF ICCS network design and loading analysis

    International Nuclear Information System (INIS)

    Tietbohl, G; Bryant, R


    The National Ignition Facility (NIF) is housed within a large facility about the size of two football fields. The Integrated Computer Control System (ICCS) is distributed throughout this facility and requires the integration of about 40,000 control points and over 500 video sources. This integration is provided by approximately 700 control computers distributed throughout the NIF facility and a network that provides the communication infrastructure. A main control room houses a set of seven computer consoles providing operator access and control of the various distributed front-end processors (FEPs). There are also remote workstations distributed within the facility that allow provide operator console functions while personnel are testing and troubleshooting throughout the facility. The operator workstations communicate with the FEPs which implement the localized control and monitoring functions. There are different types of FEPs for the various subsystems being controlled. This report describes the design of the NIF ICCS network and how it meets the traffic loads that will are expected and the requirements of the Sub-System Design Requirements (SSDR's). This document supersedes the earlier reports entitled Analysis of the National Ignition Facility Network, dated November 6, 1996 and The National Ignition Facility Digital Video and Control Network, dated July 9, 1996. For an overview of the ICCS, refer to the document NIF Integrated Computer Controls System Description (NIF-3738)

  14. Analysis of Nonstationary Time Series for Biological Rhythms Research. (United States)

    Leise, Tanya L


    This article is part of a Journal of Biological Rhythms series exploring analysis and statistics topics relevant to researchers in biological rhythms and sleep research. The goal is to provide an overview of the most common issues that arise in the analysis and interpretation of data in these fields. In this article on time series analysis for biological rhythms, we describe some methods for assessing the rhythmic properties of time series, including tests of whether a time series is indeed rhythmic. Because biological rhythms can exhibit significant fluctuations in their period, phase, and amplitude, their analysis may require methods appropriate for nonstationary time series, such as wavelet transforms, which can measure how these rhythmic parameters change over time. We illustrate these methods using simulated and real time series.

  15. Analysis of biological spectrum of Divčibare flora

    Directory of Open Access Journals (Sweden)

    Popović Ivana


    Full Text Available One of the essential analyses which is performed during the floristic study of a region is the analysis of the biological spectrum. The analysis of the biological spectrum of the flora includes the determination of the type of life form for each taxon described in the flora of the study region. If it is considered that life form is a specific structural-functional response to the environmental effects and the result of the adaptation during the species evolution, it is clear that the basic characteristics of the site are more or less reflected in any life form. This fact is confirmed by the analysis of the biological spectrum of Divčibare flora. The study results are in correlation with the results of the analysis of the biological spectrum of the flora of Serbia and the Balkan Peninsula.

  16. Human · mouse genome analysis and radiation biology. Proceedings

    International Nuclear Information System (INIS)

    Hori, Tada-aki


    This issue is the collection of the papers presented at the 25th NIRS symposium on Human, Mouse Genome Analysis and Radiation Biology. The 14 of the presented papers are indexed individually. (J.P.N.)

  17. Computational Modeling, Formal Analysis, and Tools for Systems Biology.

    Directory of Open Access Journals (Sweden)

    Ezio Bartocci


    Full Text Available As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.

  18. Methods for analysis of fluoroquinolones in biological fluids (United States)

    Methods for analysis of 10 selected fluoroquinolone antibiotics in biological fluids are reviewed. Approaches for sample preparation, detection methods, limits of detection and quantitation and recovery information are provided for both single analyte and multi-analyte fluoroquinolone methods....

  19. The Application of Social Network Analysis to Team Sports (United States)

    Lusher, Dean; Robins, Garry; Kremer, Peter


    This article reviews how current social network analysis might be used to investigate individual and group behavior in sporting teams. Social network analysis methods permit researchers to explore social relations between team members and their individual-level qualities simultaneously. As such, social network analysis can be seen as augmenting…

  20. Analysis and visualization of citation networks

    CERN Document Server

    Zhao, Dangzhi


    Citation analysis-the exploration of reference patterns in the scholarly and scientific literature-has long been applied in a number of social sciences to study research impact, knowledge flows, and knowledge networks. It has important information science applications as well, particularly in knowledge representation and in information retrieval.Recent years have seen a burgeoning interest in citation analysis to help address research, management, or information service issues such as university rankings, research evaluation, or knowledge domain visualization. This renewed and growing interest

  1. An Intelligent technical analysis using neural network

    Directory of Open Access Journals (Sweden)

    Reza Raei


    Full Text Available Technical analysis has been one of the most popular methods for stock market predictions for the past few decades. There have been enormous technical analysis methods to study the behavior of stock market for different kinds of trading markets such as currency, commodity or stock. In this paper, we propose two different methods based on volume adjusted moving average and ease of movement for stock trading. These methods are used with and without generalized regression neural network methods and the results are compared with each other. The preliminary results on historical stock price of 20 firms indicate that there is no meaningful difference between various proposed models of this paper.

  2. Phosphoproteomics-based systems analysis of signal transduction networks

    Directory of Open Access Journals (Sweden)

    Hiroko eKozuka-Hata


    Full Text Available Signal transduction systems coordinate complex cellular information to regulate biological events such as cell proliferation and differentiation. Although the accumulating evidence on widespread association of signaling molecules has revealed essential contribution of phosphorylation-dependent interaction networks to cellular regulation, their dynamic behavior is mostly yet to be analyzed. Recent technological advances regarding mass spectrometry-based quantitative proteomics have enabled us to describe the comprehensive status of phosphorylated molecules in a time-resolved manner. Computational analyses based on the phosphoproteome dynamics accelerate generation of novel methodologies for mathematical analysis of cellular signaling. Phosphoproteomics-based numerical modeling can be used to evaluate regulatory network elements from a statistical point of view. Integration with transcriptome dynamics also uncovers regulatory hubs at the transcriptional level. These omics-based computational methodologies, which have firstly been applied to representative signaling systems such as the epidermal growth factor receptor pathway, have now opened up a gate for systems analysis of signaling networks involved in immune response and cancer.

  3. A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. (United States)

    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; Le Novère, Nicolas; 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; Kirdar, Betül; Penttilä, Merja; Klipp, Edda; Palsson, Bernhard Ø; Sauer, Uwe; Oliver, Stephen G; Mendes, Pedro; Nielsen, Jens; Kell, Douglas B


    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 content, and use different terminologies to describe the same chemical entities. This makes comparisons between them difficult and underscores the desirability of a consolidated metabolic network that collects and formalizes the 'community knowledge' of yeast metabolism. We describe how we have produced a consensus metabolic network reconstruction for S. cerevisiae. In drafting it, we placed special emphasis on referencing molecules to persistent databases or using database-independent forms, such as SMILES or InChI strings, as this permits their chemical structure to be represented unambiguously and in a manner that permits automated reasoning. The reconstruction is readily available via a publicly accessible database and in the Systems Biology Markup Language ( It can be maintained as a resource that serves as a common denominator for studying the systems biology of yeast. Similar strategies should benefit communities studying genome-scale metabolic networks of other organisms.

  4. The network researchers' network: A social network analysis of the IMP Group 1985-2006

    DEFF Research Database (Denmark)

    Henneberg, Stephan C. M.; Ziang, Zhizhong; Naudé, Peter

    ). In this paper, based upon the papers presented at the 22 conferences held to date, we undertake a Social Network Analysis in order to examine the degree of co-publishing that has taken place between this group of researchers. We identify the different components in this database, and examine the large main......The Industrial Marketing and Purchasing (IMP) Group is a network of academic researchers working in the area of business-to-business marketing. The group meets every year to discuss and exchange ideas, with a conference having been held every year since 1984 (there was no meeting in 1987...

  5. Bystander effect: Biological endpoints and microarray analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhry, M. Ahmad [Department of Medical Laboratory and Radiation Sciences, College of Nursing and Health Sciences, University of Vermont, 302 Rowell Building, Burlington, VT 05405 (United States) and DNA Microarray Facility, University of Vermont, Burlington, VT 05405 (United States)]. E-mail:


    In cell populations exposed to ionizing radiation, the biological effects occur in a much larger proportion of cells than are estimated to be traversed by radiation. It has been suggested that irradiated cells are capable of providing signals to the neighboring unirradiated cells resulting in damage to these cells. This phenomenon is termed the bystander effect. The bystander effect induces persistent, long-term, transmissible changes that result in delayed death and neoplastic transformation. Because the bystander effect is relevant to carcinogenesis, it could have significant implications for risk estimation for radiation exposure. The nature of the bystander effect signal and how it impacts the unirradiated cells remains to be elucidated. Examination of the changes in gene expression could provide clues to understanding the bystander effect and could define the signaling pathways involved in sustaining damage to these cells. The microarray technology serves as a tool to gain insight into the molecular pathways leading to bystander effect. Using medium from irradiated normal human diploid lung fibroblasts as a model system we examined gene expression alterations in bystander cells. The microarray data revealed that the radiation-induced gene expression profile in irradiated cells is different from unirradiated bystander cells suggesting that the pathways leading to biological effects in the bystander cells are different from the directly irradiated cells. The genes known to be responsive to ionizing radiation were observed in irradiated cells. Several genes were upregulated in cells receiving media from irradiated cells. Surprisingly no genes were found to be downregulated in these cells. A number of genes belonging to extracellular signaling, growth factors and several receptors were identified in bystander cells. Interestingly 15 genes involved in the cell communication processes were found to be upregulated. The induction of receptors and the cell

  6. Bystander effect: Biological endpoints and microarray analysis

    International Nuclear Information System (INIS)

    Chaudhry, M. Ahmad


    In cell populations exposed to ionizing radiation, the biological effects occur in a much larger proportion of cells than are estimated to be traversed by radiation. It has been suggested that irradiated cells are capable of providing signals to the neighboring unirradiated cells resulting in damage to these cells. This phenomenon is termed the bystander effect. The bystander effect induces persistent, long-term, transmissible changes that result in delayed death and neoplastic transformation. Because the bystander effect is relevant to carcinogenesis, it could have significant implications for risk estimation for radiation exposure. The nature of the bystander effect signal and how it impacts the unirradiated cells remains to be elucidated. Examination of the changes in gene expression could provide clues to understanding the bystander effect and could define the signaling pathways involved in sustaining damage to these cells. The microarray technology serves as a tool to gain insight into the molecular pathways leading to bystander effect. Using medium from irradiated normal human diploid lung fibroblasts as a model system we examined gene expression alterations in bystander cells. The microarray data revealed that the radiation-induced gene expression profile in irradiated cells is different from unirradiated bystander cells suggesting that the pathways leading to biological effects in the bystander cells are different from the directly irradiated cells. The genes known to be responsive to ionizing radiation were observed in irradiated cells. Several genes were upregulated in cells receiving media from irradiated cells. Surprisingly no genes were found to be downregulated in these cells. A number of genes belonging to extracellular signaling, growth factors and several receptors were identified in bystander cells. Interestingly 15 genes involved in the cell communication processes were found to be upregulated. The induction of receptors and the cell

  7. Using probabilistic graphical models to reconstruct biological networks and linkage maps

    NARCIS (Netherlands)

    Wang, Huange


    Probabilistic graphical models (PGMs) offer a conceptual architecture where biological and mathematical objects can be expressed with a common, intuitive formalism. This facilitates the joint development of statistical and computational tools for quantitative analysis of biological data. Over the

  8. Hearing health network: a spatial analysis

    Directory of Open Access Journals (Sweden)

    Camila Ferreira de Rezende


    Full Text Available INTRODUCTION: In order to meet the demands of the patient population with hearing impairment, the Hearing Health Care Network was created, consisting of primary care actions of medium and high complexity. Spatial analysis through geoprocessing is a way to understand the organization of such services. OBJECTIVE: To analyze the organization of the Hearing Health Care Network of the State of Minas Gerais. METHODS: Cross-sectional analytical study using geoprocessing techniques. The absolute frequency and the frequency per 1000 inhabitants of the following variables were analyzed: assessment and diagnosis, selection and adaptation of hearing aids, follow-up, and speech therapy. The spatial analysis unit was the health micro-region. RESULTS: The assessment and diagnosis, selection, and adaptation of hearing aids and follow-up had a higher absolute number in the micro-regions with hearing health services. The follow-up procedure showed the lowest occurrence. Speech therapy showed higher occurrence in the state, both in absolute numbers, as well as per population. CONCLUSION: The use of geoprocessing techniques allowed the identification of the care flow as a function of the procedure performance frequency, population concentration, and territory distribution. All procedures offered by the Hearing Health Care Network are performed for users of all micro-regions of the state.

  9. Design Criteria For Networked Image Analysis System (United States)

    Reader, Cliff; Nitteberg, Alan


    Image systems design is currently undergoing a metamorphosis from the conventional computing systems of the past into a new generation of special purpose designs. This change is motivated by several factors, notably among which is the increased opportunity for high performance with low cost offered by advances in semiconductor technology. Another key issue is a maturing in understanding of problems and the applicability of digital processing techniques. These factors allow the design of cost-effective systems that are functionally dedicated to specific applications and used in a utilitarian fashion. Following an overview of the above stated issues, the paper presents a top-down approach to the design of networked image analysis systems. The requirements for such a system are presented, with orientation toward the hospital environment. The three main areas are image data base management, viewing of image data and image data processing. This is followed by a survey of the current state of the art, covering image display systems, data base techniques, communications networks and software systems control. The paper concludes with a description of the functional subystems and architectural framework for networked image analysis in a production environment.

  10. Integration Strategy Is a Key Step in Network-Based Analysis and Dramatically Affects Network Topological Properties and Inferring Outcomes

    Directory of Open Access Journals (Sweden)

    Nana Jin


    Full Text Available An increasing number of experiments have been designed to detect intracellular and intercellular molecular interactions. Based on these molecular interactions (especially protein interactions, molecular networks have been built for using in several typical applications, such as the discovery of new disease genes and the identification of drug targets and molecular complexes. Because the data are incomplete and a considerable number of false-positive interactions exist, protein interactions from different sources are commonly integrated in network analyses to build a stable molecular network. Although various types of integration strategies are being applied in current studies, the topological properties of the networks from these different integration strategies, especially typical applications based on these network integration strategies, have not been rigorously evaluated. In this paper, systematic analyses were performed to evaluate 11 frequently used methods using two types of integration strategies: empirical and machine learning methods. The topological properties of the networks of these different integration strategies were found to significantly differ. Moreover, these networks were found to dramatically affect the outcomes of typical applications, such as disease gene predictions, drug target detections, and molecular complex identifications. The analysis presented in this paper could provide an important basis for future network-based biological researches.

  11. Analysis of the enzyme network involved in cattle milk production using graph theory. (United States)

    Ghorbani, Sholeh; Tahmoorespur, Mojtaba; Masoudi Nejad, Ali; Nasiri, Mohammad; Asgari, Yazdan


    Understanding cattle metabolism and its relationship with milk products is important in bovine breeding. A systemic view could lead to consequences that will result in a better understanding of existing concepts. Topological indices and quantitative characterizations mostly result from the application of graph theory on biological data. In the present work, the enzyme network involved in cattle milk production was reconstructed and analyzed based on available bovine genome information using several public datasets (NCBI, Uniprot, KEGG, and Brenda). The reconstructed network consisted of 3605 reactions named by KEGG compound numbers and 646 enzymes that catalyzed the corresponding reactions. The characteristics of the directed and undirected network were analyzed using Graph Theory. The mean path length was calculated to be4.39 and 5.41 for directed and undirected networks, respectively. The top 11 hub enzymes whose abnormality could harm bovine health and reduce milk production were determined. Therefore, the aim of constructing the enzyme centric network was twofold; first to find out whether such network followed the same properties of other biological networks, and second, to find the key enzymes. The results of the present study can improve our understanding of milk production in cattle. Also, analysis of the enzyme network can help improve the modeling and simulation of biological systems and help design desired phenotypes to increase milk production quality or quantity.

  12. Integrated Adaptive Analysis and Visualization of Satellite Network Data Project (United States)

    National Aeronautics and Space Administration — We propose to develop a system that enables integrated and adaptive analysis and visualization of satellite network management data. Integrated analysis and...

  13. Understanding resilience in industrial symbiosis networks: insights from network analysis. (United States)

    Chopra, Shauhrat S; Khanna, Vikas


    Industrial symbiotic networks are based on the principles of ecological systems where waste equals food, to develop synergistic networks. For example, industrial symbiosis (IS) at Kalundborg, Denmark, creates an exchange network of waste, water, and energy among companies based on contractual dependency. Since most of the industrial symbiotic networks are based on ad-hoc opportunities rather than strategic planning, gaining insight into disruptive scenarios is pivotal for understanding the balance of resilience and sustainability and developing heuristics for designing resilient IS networks. The present work focuses on understanding resilience as an emergent property of an IS network via a network-based approach with application to the Kalundborg Industrial Symbiosis (KIS). Results from network metrics and simulated disruptive scenarios reveal Asnaes power plant as the most critical node in the system. We also observe a decrease in the vulnerability of nodes and reduction in single points of failure in the system, suggesting an increase in the overall resilience of the KIS system from 1960 to 2010. Based on our findings, we recommend design strategies, such as increasing diversity, redundancy, and multi-functionality to ensure flexibility and plasticity, to develop resilient and sustainable industrial symbiotic networks. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Network Graph Analysis of Gene-Gene Interactions in Genome-Wide Association Study Data

    Directory of Open Access Journals (Sweden)

    Sungyoung Lee


    Full Text Available Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs. For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR is one of the powerful and efficient methods for detecting high-order gene-gene (GxG interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI. Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

  15. Uranium-233 analysis of biological samples

    International Nuclear Information System (INIS)

    Gies, R.A.; Ballou, J.E.; Case, A.C.


    Two liquid scintillation techniques were compared for 233 U analysis: a two-phase extraction system (D2EHPA) developed by Keough and Powers, 1970, for Pu analysis; and a single-phase emulsion system (TT21) that holds the total sample in suspension with the scintillator. The first system (D2EHPA) was superior in reducing background (two- to threefold) and in accommodating a larger sample volume (fivefold). Samples containing > 50 mg/ml of slats were not extracted quantitatively by D2EHPA

  16. Convolutional Deep Belief Networks for Single-Cell/Object Tracking in Computational Biology and Computer Vision


    Zhong, Bineng; Pan, Shengnan; Zhang, Hongbo; Wang, Tian; Du, Jixiang; Chen, Duansheng; Cao, Liujuan


    In this paper, we propose deep architecture to dynamically learn the most discriminative features from data for both single-cell and object tracking in computational biology and computer vision. Firstly, the discriminative features are automatically learned via a convolutional deep belief network (CDBN). Secondly, we design a simple yet effective method to transfer features learned from CDBNs on the source tasks for generic purpose to the object tracking tasks using only limited amount of tra...

  17. Yeast Biological Networks Unfold the Interplay of Antioxidants, Genome and Phenotype, and Reveal a Novel Regulator of the Oxidative Stress Response

    DEFF Research Database (Denmark)

    Otero, José Manuel; Papadakis, M.A.; Udatha, D.B.R.K.G.


    Background: Identifying causative biological networks associated with relevant phenotypes is essential in the field of systems biology. We used ferulic acid (FA) as a model antioxidant to characterize the global expression programs triggered by this small molecule and decipher the transcriptional...... network controlling the phenotypic adaptation of the yeast Saccharomyces cerevisiae. Methodology/Principal Findings: By employing a strict cut off value during gene expression data analysis, 106 genes were found to be involved in the cell response to FA, independent of aerobic or anaerobic conditions....... Network analysis of the system guided us to a key target node, the FMP43 protein, that when deleted resulted in marked acceleration of cellular growth (similar to 15% in both minimal and rich media). To extend our findings to human cells and identify proteins that could serve as drug targets, we replaced...

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

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


    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

  19. A Multilevel Gamma-Clustering Layout Algorithm for Visualization of Biological Networks (United States)

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


    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

  20. Recurrent Convolutional Neural Networks: A Better Model of Biological Object Recognition. (United States)

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


    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.

  1. Gene regulatory network reconstruction using Bayesian networks, the Dantzig Selector, the Lasso and their meta-analysis.

    Directory of Open Access Journals (Sweden)

    Matthieu Vignes

    Full Text Available Modern technologies and especially next generation sequencing facilities are giving a cheaper access to genotype and genomic data measured on the same sample at once. This creates an ideal situation for multifactorial experiments designed to infer gene regulatory networks. The fifth "Dialogue for Reverse Engineering Assessments and Methods" (DREAM5 challenges are aimed at assessing methods and associated algorithms devoted to the inference of biological networks. Challenge 3 on "Systems Genetics" proposed to infer causal gene regulatory networks from different genetical genomics data sets. We investigated a wide panel of methods ranging from Bayesian networks to penalised linear regressions to analyse such data, and proposed a simple yet very powerful meta-analysis, which combines these inference methods. We present results of the Challenge as well as more in-depth analysis of predicted networks in terms of structure and reliability. The developed meta-analysis was ranked first among the 16 teams participating in Challenge 3A. It paves the way for future extensions of our inference method and more accurate gene network estimates in the context of genetical genomics.

  2. Integrating Bayesian variable selection with Modular Response Analysis to infer biochemical network topology. (United States)

    Santra, Tapesh; Kolch, Walter; Kholodenko, Boris N


    Recent advancements in genetics and proteomics have led to the acquisition of large quantitative data sets. However, the use of these data to reverse engineer biochemical networks has remained a challenging problem. Many methods have been proposed to infer biochemical network topologies from different types of biological data. Here, we focus on unraveling network topologies from steady state responses of biochemical networks to successive experimental perturbations. We propose a computational algorithm which combines a deterministic network inference method termed Modular Response Analysis (MRA) and a statistical model selection algorithm called Bayesian Variable Selection, to infer functional interactions in cellular signaling pathways and gene regulatory networks. It can be used to identify interactions among individual molecules involved in a biochemical pathway or reveal how different functional modules of a biological network interact with each other to exchange information. In cases where not all network components are known, our method reveals functional interactions which are not direct but correspond to the interaction routes through unknown elements. Using computer simulated perturbation responses of signaling pathways and gene regulatory networks from the DREAM challenge, we demonstrate that the proposed method is robust against noise and scalable to large networks. We also show that our method can infer network topologies using incomplete perturbation datasets. Consequently, we have used this algorithm to explore the ERBB regulated G1/S transition pathway in certain breast cancer cells to understand the molecular mechanisms which cause these cells to become drug resistant. The algorithm successfully inferred many well characterized interactions of this pathway by analyzing experimentally obtained perturbation data. Additionally, it identified some molecular interactions which promote drug resistance in breast cancer cells. The proposed algorithm

  3. Applications of social media and social network analysis

    CERN Document Server

    Kazienko, Przemyslaw


    This collection of contributed chapters demonstrates a wide range of applications within two overlapping research domains: social media analysis and social network analysis. Various methodologies were utilized in the twelve individual chapters including static, dynamic and real-time approaches to graph, textual and multimedia data analysis. The topics apply to reputation computation, emotion detection, topic evolution, rumor propagation, evaluation of textual opinions, friend ranking, analysis of public transportation networks, diffusion in dynamic networks, analysis of contributors to commun

  4. Comparative analysis of weighted gene co-expression networks in human and mouse. (United States)

    Eidsaa, Marius; Stubbs, Lisa; Almaas, Eivind


    The application of complex network modeling to analyze large co-expression data sets has gained traction during the last decade. In particular, the use of the weighted gene co-expression network analysis framework has allowed an unbiased and systems-level investigation of genotype-phenotype relationships in a wide range of systems. Since mouse is an important model organism for biomedical research on human disease, it is of great interest to identify similarities and differences in the functional roles of human and mouse orthologous genes. Here, we develop a novel network comparison approach which we demonstrate by comparing two gene-expression data sets from a large number of human and mouse tissues. The method uses weighted topological overlap alongside the recently developed network-decomposition method of s-core analysis, which is suitable for making gene-centrality rankings for weighted networks. The aim is to identify globally central genes separately in the human and mouse networks. By comparing the ranked gene lists, we identify genes that display conserved or diverged centrality-characteristics across the networks. This framework only assumes a single threshold value that is chosen from a statistical analysis, and it may be applied to arbitrary network structures and edge-weight distributions, also outside the context of biology. When conducting the comparative network analysis, both within and across the two species, we find a clear pattern of enrichment of transcription factors, for the homeobox domain in particular, among the globally central genes. We also perform gene-ontology term enrichment analysis and look at disease-related genes for the separate networks as well as the network comparisons. We find that gene ontology terms related to regulation and development are generally enriched across the networks. In particular, the genes FOXE3, RHO, RUNX2, ALX3 and RARA, which are disease genes in either human or mouse, are on the top-10 list of globally

  5. Analysis of complex systems using neural networks

    International Nuclear Information System (INIS)

    Uhrig, R.E.


    The application of neural networks, alone or in conjunction with other advanced technologies (expert systems, fuzzy logic, and/or genetic algorithms), to some of the problems of complex engineering systems has the potential to enhance the safety, reliability, and operability of these systems. Typically, the measured variables from the systems are analog variables that must be sampled and normalized to expected peak values before they are introduced into neural networks. Often data must be processed to put it into a form more acceptable to the neural network (e.g., a fast Fourier transformation of the time-series data to produce a spectral plot of the data). Specific applications described include: (1) Diagnostics: State of the Plant (2) Hybrid System for Transient Identification, (3) Sensor Validation, (4) Plant-Wide Monitoring, (5) Monitoring of Performance and Efficiency, and (6) Analysis of Vibrations. Although specific examples described deal with nuclear power plants or their subsystems, the techniques described can be applied to a wide variety of complex engineering systems

  6. Network analysis of psychopathy in forensic patients. (United States)

    Preszler, Jonathan; Marcus, David K; Edens, John F; McDermott, Barbara E


    The question of which features represent the most central components of psychopathy remains unresolved and is the subject of considerable debate. Network analysis, which is a relatively new way to conceptualize mental disorders that emphasizes complex causal systems, provides a means to graphically and quantitatively describe the centrality of the various symptoms of a disorder. We applied association and adaptive LASSO networks on two samples of forensic patients. The first sample included forensic inpatients (N = 277) who were administered the Psychopathy Checklist-Revised (Hare, 2003), and the second sample included patients who previously had been civilly committed (N = 1136), who were administered the Psychopathy Checklist: Screening Version (Hart, Cox, & Hare, 1995). The models indicated the items on the affective facet are highly central across both samples and methods, and the item "lack of remorse" was especially central to the networks. Conversely, interpersonal, lifestyle, and antisocial facets generally resulted in low centrality in the models of both samples. Thus, the models lend support to the importance of affective deficits as the primary feature of psychopathy when psychopathy is assessed using the Hare Psychopathy Checklist measures. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  7. Mixed Methods Analysis of Enterprise Social Networks

    DEFF Research Database (Denmark)

    Behrendt, Sebastian; Richter, Alexander; Trier, Matthias


    The increasing use of enterprise social networks (ESN) generates vast amounts of data, giving researchers and managerial decision makers unprecedented opportunities for analysis. However, more transparency about the available data dimensions and how these can be combined is needed to yield accurate...... insights into the multi-facetted phenomenon of ESN use. In order to address this issue, we first conducted a systematic literature review to identify available data dimensions and integrated them into a conceptual framework. We then adopted this framework as part of a mixed methods research approach...

  8. Social sciences via network analysis and computation

    CERN Document Server

    Kanduc, Tadej


    In recent years information and communication technologies have gained significant importance in the social sciences. Because there is such rapid growth of knowledge, methods and computer infrastructure, research can now seamlessly connect interdisciplinary fields such as business process management, data processing and mathematics. This study presents some of the latest results, practices and state-of-the-art approaches in network analysis, machine learning, data mining, data clustering and classifications in the contents of social sciences. It also covers various real-life examples such as t

  9. Quantitative utilization of prior biological knowledge in the Bayesian network modeling of gene expression data

    Directory of Open Access Journals (Sweden)

    Gao Shouguo


    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.

  10. A systems biology approach to reconcile metabolic network models with application to Synechocystis sp. PCC 6803 for biofuel production. (United States)

    Mohammadi, Reza; Fallah-Mehrabadi, Jalil; Bidkhori, Gholamreza; Zahiri, Javad; Javad Niroomand, Mohammad; Masoudi-Nejad, Ali


    Production of biofuels has been one of the promising efforts in biotechnology in the past few decades. The perspective of these efforts can be reduction of increasing demands for fossil fuels and consequently reducing environmental pollution. Nonetheless, most previous approaches did not succeed in obviating many big challenges in this way. In recent years systems biology with the help of microorganisms has been trying to overcome these challenges. Unicellular cyanobacteria are widespread phototrophic microorganisms that have capabilities such as consuming solar energy and atmospheric carbon dioxide for growth and thus can be a suitable chassis for the production of valuable organic materials such as biofuels. For the ultimate use of metabolic potential of cyanobacteria, it is necessary to understand the reactions that are taking place inside the metabolic network of these microorganisms. In this study, we developed a Java tool to reconstruct an integrated metabolic network of a cyanobacterium (Synechocystis sp. PCC 6803). We merged three existing reconstructed metabolic networks of this microorganism. Then, after modeling for biofuel production, the results from flux balance analysis (FBA) disclosed an increased yield in biofuel production for ethanol, isobutanol, 3-methyl-1-butanol, 2-methyl-1-butanol, and propanol. The numbers of blocked reactions were also decreased for 2-methyl-1-butanol production. In addition, coverage of the metabolic network in terms of the number of metabolites and reactions was increased in the new obtained model.

  11. Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks (United States)

    Mehta, Pankaj; Lang, Alex H.; Schwab, David J.


    A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.

  12. Architecture and biological applications of artificial neural networks: a tuberculosis perspective. (United States)

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


    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.

  13. Module-based association analysis for omics data with network structure. (United States)

    Wang, Zhi; Maity, Arnab; Hsiao, Chuhsing Kate; Voora, Deepak; Kaddurah-Daouk, Rima; Tzeng, Jung-Ying


    Module-based analysis (MBA) aims to evaluate the effect of a group of biological elements sharing common features, such as SNPs in the same gene or metabolites in the same pathways, and has become an attractive alternative to traditional single bio-element approaches. Because bio-elements regulate and interact with each other as part of network, incorporating network structure information can more precisely model the biological effects, enhance the ability to detect true associations, and facilitate our understanding of the underlying biological mechanisms. However, most MBA methods ignore the network structure information, which depicts the interaction and regulation relationship among basic functional units in biology system. We construct the connectivity kernel and the topology kernel to capture the relationship among bio-elements in a module, and use a kernel machine framework to evaluate the joint effect of bio-elements. Our proposed kernel machine approach directly incorporates network structure so to enhance the study efficiency; it can assess interactions among modules, account covariates, and is computational efficient. Through simulation studies and real data application, we demonstrate that the proposed network-based methods can have markedly better power than the approaches ignoring network information under a range of scenarios.

  14. A basic analysis toolkit for biological sequences

    Directory of Open Access Journals (Sweden)

    Siragusa Enrico


    Full Text Available Abstract This paper presents a software library, nicknamed BATS, for some basic sequence analysis tasks. Namely, local alignments, via approximate string matching, and global alignments, via longest common subsequence and alignments with affine and concave gap cost functions. Moreover, it also supports filtering operations to select strings from a set and establish their statistical significance, via z-score computation. None of the algorithms is new, but although they are generally regarded as fundamental for sequence analysis, they have not been implemented in a single and consistent software package, as we do here. Therefore, our main contribution is to fill this gap between algorithmic theory and practice by providing an extensible and easy to use software library that includes algorithms for the mentioned string matching and alignment problems. The library consists of C/C++ library functions as well as Perl library functions. It can be interfaced with Bioperl and can also be used as a stand-alone system with a GUI. The software is available at under the GNU GPL.

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

    Directory of Open Access Journals (Sweden)

    Sharp Burt M


    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 can be accessed free of charge to academic users.

  16. Category Theoretic Analysis of Hierarchical Protein Materials and Social Networks (United States)

    Spivak, David I.; Giesa, Tristan; Wood, Elizabeth; Buehler, Markus J.


    Materials in biology span all the scales from Angstroms to meters and typically consist of complex hierarchical assemblies of simple building blocks. Here we describe an application of category theory to describe structural and resulting functional properties of biological protein materials by developing so-called ologs. An olog is like a “concept web” or “semantic network” except that it follows a rigorous mathematical formulation based on category theory. This key difference ensures that an olog is unambiguous, highly adaptable to evolution and change, and suitable for sharing concepts with other olog. We consider simple cases of beta-helical and amyloid-like protein filaments subjected to axial extension and develop an olog representation of their structural and resulting mechanical properties. We also construct a representation of a social network in which people send text-messages to their nearest neighbors and act as a team to perform a task. We show that the olog for the protein and the olog for the social network feature identical category-theoretic representations, and we proceed to precisely explicate the analogy or isomorphism between them. The examples presented here demonstrate that the intrinsic nature of a complex system, which in particular includes a precise relationship between structure and function at different hierarchical levels, can be effectively represented by an olog. This, in turn, allows for comparative studies between disparate materials or fields of application, and results in novel approaches to derive functionality in the design of de novo hierarchical systems. We discuss opportunities and challenges associated with the description of complex biological materials by using ologs as a powerful tool for analysis and design in the context of materiomics, and we present the potential impact of this approach for engineering, life sciences, and medicine. PMID:21931622

  17. Using chemistry and microfluidics to understand the spatial dynamics of complex biological networks. (United States)

    Kastrup, Christian J; Runyon, Matthew K; Lucchetta, Elena M; Price, Jessica M; Ismagilov, Rustem F


    Understanding the spatial dynamics of biochemical networks is both fundamentally important for understanding life at the systems level and also has practical implications for medicine, engineering, biology, and chemistry. Studies at the level of individual reactions provide essential information about the function, interactions, and localization of individual molecular species and reactions in a network. However, analyzing the spatial dynamics of complex biochemical networks at this level is difficult. Biochemical networks are nonequilibrium systems containing dozens to hundreds of reactions with nonlinear and time-dependent interactions, and these interactions are influenced by diffusion, flow, and the relative values of state-dependent kinetic parameters. To achieve an overall understanding of the spatial dynamics of a network and the global mechanisms that drive its function, networks must be analyzed as a whole, where all of the components and influential parameters of a network are simultaneously considered. Here, we describe chemical concepts and microfluidic tools developed for network-level investigations of the spatial dynamics of these networks. Modular approaches can be used to simplify these networks by separating them into modules, and simple experimental or computational models can be created by replacing each module with a single reaction. Microfluidics can be used to implement these models as well as to analyze and perturb the complex network itself with spatial control on the micrometer scale. We also describe the application of these network-level approaches to elucidate the mechanisms governing the spatial dynamics of two networkshemostasis (blood clotting) and early patterning of the Drosophila embryo. To investigate the dynamics of the complex network of hemostasis, we simplified the network by using a modular mechanism and created a chemical model based on this mechanism by using microfluidics. Then, we used the mechanism and the model to

  18. Identifying changes in the support networks of end-of-life carers using social network analysis. (United States)

    Leonard, Rosemary; Horsfall, Debbie; Noonan, Kerrie


    End-of-life caring is often associated with reduced social networks for both the dying person and for the carer. However, those adopting a community participation and development approach, see the potential for the expansion and strengthening of networks. This paper uses Knox, Savage and Harvey's definitions of three generations social network analysis to analyse the caring networks of people with a terminal illness who are being cared for at home and identifies changes in these caring networks that occurred over the period of caring. Participatory network mapping of initial and current networks was used in nine focus groups. The analysis used key concepts from social network analysis (size, density, transitivity, betweenness and local clustering) together with qualitative analyses of the group's reflections on the maps. The results showed an increase in the size of the networks and that ties between the original members of the network strengthened. The qualitative data revealed the importance between core and peripheral network members and the diverse contributions of the network members. The research supports the value of third generation social network analysis and the potential for end-of-life caring to build social capital. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  19. Robustness Analysis of Real Network Topologies Under Multiple Failure Scenarios

    DEFF Research Database (Denmark)

    Manzano, M.; Marzo, J. L.; Calle, E.


    on topological characteristics. Recently approaches also consider the services supported by such networks. In this paper we carry out a robustness analysis of five real backbone telecommunication networks under defined multiple failure scenarios, taking into account the consequences of the loss of established......Nowadays the ubiquity of telecommunication networks, which underpin and fulfill key aspects of modern day living, is taken for granted. Significant large-scale failures have occurred in the last years affecting telecommunication networks. Traditionally, network robustness analysis has been focused...... connections. Results show which networks are more robust in response to a specific type of failure....

  20. Network based transcription factor analysis of regenerating axolotl limbs

    Directory of Open Access Journals (Sweden)

    Cameron Jo Ann


    Full Text Available Abstract Background Studies on amphibian limb regeneration began in the early 1700's but we still do not completely understand the cellular and molecular events of this unique process. Understanding a complex biological process such as limb regeneration is more complicated than the knowledge of the individual genes or proteins involved. Here we followed a systems biology approach in an effort to construct the networks and pathways of protein interactions involved in formation of the accumulation blastema in regenerating axolotl limbs. Results We used the human orthologs of proteins previously identified by our research team as bait to identify the transcription factor (TF pathways and networks that regulate blastema formation in amputated axolotl limbs. The five most connected factors, c-Myc, SP1, HNF4A, ESR1 and p53 regulate ~50% of the proteins in our data. Among these, c-Myc and SP1 regulate 36.2% of the proteins. c-Myc was the most highly connected TF (71 targets. Network analysis showed that TGF-β1 and fibronectin (FN lead to the activation of these TFs. We found that other TFs known to be involved in epigenetic reprogramming, such as Klf4, Oct4, and Lin28 are also connected to c-Myc and SP1. Conclusions Our study provides a systems biology approach to how different molecular entities inter-connect with each other during the formation of an accumulation blastema in regenerating axolotl limbs. This approach provides an in silico methodology to identify proteins that are not detected by experimental methods such as proteomics but are potentially important to blastema formation. We found that the TFs, c-Myc and SP1 and their target genes could potentially play a central role in limb regeneration. Systems biology has the potential to map out numerous other pathways that are crucial to blastema formation in regeneration-competent limbs, to compare these to the pathways that characterize regeneration-deficient limbs and finally, to identify stem

  1. On the Optimality of Trust Network Analysis with Subjective Logic


    PARK, Y.


    Building and measuring trust is one of crucial aspects in e-commerce, social networking and computer security. Trust networks are widely used to formalize trust relationships and to conduct formal reasoning of trust values. Diverse trust network analysis methods have been developed so far and one of the most widely used schemes is TNA-SL (Trust Network Analysis with Subjective Logic). Recent papers claimed that TNA-SL always finds the optimal solution by producing the least un...

  2. Electrical circuit modeling and analysis of microwave acoustic interaction with biological tissues. (United States)

    Gao, Fei; Zheng, Qian; Zheng, Yuanjin


    Numerical study of microwave imaging and microwave-induced thermoacoustic imaging utilizes finite difference time domain (FDTD) analysis for simulation of microwave and acoustic interaction with biological tissues, which is time consuming due to complex grid-segmentation and numerous calculations, not straightforward due to no analytical solution and physical explanation, and incompatible with hardware development requiring circuit simulator such as SPICE. In this paper, instead of conventional FDTD numerical simulation, an equivalent electrical circuit model is proposed to model the microwave acoustic interaction with biological tissues for fast simulation and quantitative analysis in both one and two dimensions (2D). The equivalent circuit of ideal point-like tissue for microwave-acoustic interaction is proposed including transmission line, voltage-controlled current source, envelop detector, and resistor-inductor-capacitor (RLC) network, to model the microwave scattering, thermal expansion, and acoustic generation. Based on which, two-port network of the point-like tissue is built and characterized using pseudo S-parameters and transducer gain. Two dimensional circuit network including acoustic scatterer and acoustic channel is also constructed to model the 2D spatial information and acoustic scattering effect in heterogeneous medium. Both FDTD simulation, circuit simulation, and experimental measurement are performed to compare the results in terms of time domain, frequency domain, and pseudo S-parameters characterization. 2D circuit network simulation is also performed under different scenarios including different sizes of tumors and the effect of acoustic scatterer. The proposed circuit model of microwave acoustic interaction with biological tissue could give good agreement with FDTD simulated and experimental measured results. The pseudo S-parameters and characteristic gain could globally evaluate the performance of tumor detection. The 2D circuit network

  3. Using the Contextual Hub Analysis Tool (CHAT) in Cytoscape to Identify Contextually Relevant Network Hubs. (United States)

    Muetze, Tanja; Lynn, David J


    Highly connected nodes in biological networks are called network hubs. Hubs are topologically important to the structure of the network and have 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 provide a step-by-step protocol for using the Contextual Hub Analysis Tool (CHAT), an application within Cytoscape 3, 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 or protein expression data, and identify hub nodes that are more highly connected to contextual nodes than expected by chance. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  4. 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

  5. Efficient analysis methods in synthetic biology. (United States)

    Madsen, Curtis; Myers, Chris; Roehner, Nicholas; Winstead, Chris; Zhang, Zhen


    This chapter describes new analysis and verification techniques for synthetic genetic circuits. In particular, it applies stochastic model checking techniques to models of genetic circuits in order to ensure that they behave correctly and are as robust as possible for a variety of different inputs and parameter settings. In addition to stochastic model checking, this chapter proposes new variants to the incremental stochastic simulation algorithm (iSSA) that are capable of presenting a researcher with a simulation trace of the typical behavior of the system. Before the development of this algorithm, discerning this information was extremely error-prone as it involved performing many simulations and attempting to wade through the massive amounts of data. This algorithm greatly aids researchers in designing genetic circuits as it efficiently shows the researcher the most likely behavior of the circuit. Both the iSSA and stochastic model checking can be used in concert to give a researcher the likelihood that the system exhibits its most typical behavior, as well as, non-typical behaviors. This methodology is applied to several genetic circuits leading to new understanding of the effects of various parameters on the behavior of these circuits.

  6. Pereskia aculeata: biological analysis on wistar rats

    Directory of Open Access Journals (Sweden)

    Luciele Milani ZEM


    Full Text Available Abstract Pereskia aculeata Mill., a species of the family Cactaceous, popularly known in Brazil as ora-pro-nobis, has high protein, vitamin and mineral contents. High essential amino acid concentrations should be underscored, suggesting a better evaluation of the fractions. Current study quantifies amino acid content and the chemical score (CS of protein amino acids, determining in vivo digestibility, protein efficiency ratio (PER and net protein ratio (NPR of P. aculeata. Plant material was collected, washed, placed in an oven at 60 °C, ground and stored in a freezer for chemical analysis. Diets that maintain isoproteic and isocaloric characteristics were prepared for the bioassay, namely: casein (no protein and Pereskia aculeata leaves-based flour. Eighteen male albino Wistar rats, divided into three experimental groups of 6 animals each, were used to evaluate protein quality and bioavailability of micronutrients. Pereskia aculeata flour provided as a single source is inadequate for growth, although it is relevant for maintaining protein metabolism indicated by net protein ratio (2.87. It is actually a good quality protein source due to few limiting essential amino acids, and it meets the diet requirements for humans.

  7. Spectral Analysis Methods of Social Networks

    Directory of Open Access Journals (Sweden)

    P. G. Klyucharev


    Full Text Available Online social networks (such as Facebook, Twitter, VKontakte, etc. being an important channel for disseminating information are often used to arrange an impact on the social consciousness for various purposes - from advertising products or services to the full-scale information war thereby making them to be a very relevant object of research. The paper reviewed the analysis methods of social networks (primarily, online, based on the spectral theory of graphs. Such methods use the spectrum of the social graph, i.e. a set of eigenvalues of its adjacency matrix, and also the eigenvectors of the adjacency matrix.Described measures of centrality (in particular, centrality based on the eigenvector and PageRank, which reflect a degree of impact one or another user of the social network has. A very popular PageRank measure uses, as a measure of centrality, the graph vertices, the final probabilities of the Markov chain, whose matrix of transition probabilities is calculated on the basis of the adjacency matrix of the social graph. The vector of final probabilities is an eigenvector of the matrix of transition probabilities.Presented a method of dividing the graph vertices into two groups. It is based on maximizing the network modularity by computing the eigenvector of the modularity matrix.Considered a method for detecting bots based on the non-randomness measure of a graph to be computed using the spectral coordinates of vertices - sets of eigenvector components of the adjacency matrix of a social graph.In general, there are a number of algorithms to analyse social networks based on the spectral theory of graphs. These algorithms show very good results, but their disadvantage is the relatively high (albeit polynomial computational complexity for large graphs.At the same time it is obvious that the practical application capacity of the spectral graph theory methods is still underestimated, and it may be used as a basis to develop new methods.The work

  8. Biological conservation law as an emerging functionality in dynamical neuronal networks. (United States)

    Podobnik, Boris; Jusup, Marko; Tiganj, Zoran; Wang, Wen-Xu; Buldú, Javier M; Stanley, H Eugene


    Scientists strive to understand how functionalities, such as conservation laws, emerge in complex systems. Living complex systems in particular create high-ordered functionalities by pairing up low-ordered complementary processes, e.g., one process to build and the other to correct. We propose a network mechanism that demonstrates how collective statistical laws can emerge at a macro (i.e., whole-network) level even when they do not exist at a unit (i.e., network-node) level. Drawing inspiration from neuroscience, we model a highly stylized dynamical neuronal network in which neurons fire either randomly or in response to the firing of neighboring neurons. A synapse connecting two neighboring neurons strengthens when both of these neurons are excited and weakens otherwise. We demonstrate that during this interplay between the synaptic and neuronal dynamics, when the network is near a critical point, both recurrent spontaneous and stimulated phase transitions enable the phase-dependent processes to replace each other and spontaneously generate a statistical conservation law-the conservation of synaptic strength. This conservation law is an emerging functionality selected by evolution and is thus a form of biological self-organized criticality in which the key dynamical modes are collective.

  9. Biological modelling of a computational spiking neural network with neuronal avalanches (United States)

    Li, Xiumin; Chen, Qing; Xue, Fangzheng


    In recent years, an increasing number of studies have demonstrated that networks in the brain can self-organize into a critical state where dynamics exhibit a mixture of ordered and disordered patterns. This critical branching phenomenon is termed neuronal avalanches. It has been hypothesized that the homeostatic level balanced between stability and plasticity of this critical state may be the optimal state for performing diverse neural computational tasks. However, the critical region for high performance is narrow and sensitive for spiking neural networks (SNNs). In this paper, we investigated the role of the critical state in neural computations based on liquid-state machines, a biologically plausible computational neural network model for real-time computing. The computational performance of an SNN when operating at the critical state and, in particular, with spike-timing-dependent plasticity for updating synaptic weights is investigated. The network is found to show the best computational performance when it is subjected to critical dynamic states. Moreover, the active-neuron-dominant structure refined from synaptic learning can remarkably enhance the robustness of the critical state and further improve computational accuracy. These results may have important implications in the modelling of spiking neural networks with optimal computational performance. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

  10. Cohesion network analysis of CSCL participation. (United States)

    Dascalu, Mihai; McNamara, Danielle S; Trausan-Matu, Stefan; Allen, Laura K


    The broad use of computer-supported collaborative-learning (CSCL) environments (e.g., instant messenger-chats, forums, blogs in online communities, and massive open online courses) calls for automated tools to support tutors in the time-consuming process of analyzing collaborative conversations. In this article, the authors propose and validate the cohesion network analysis (CNA) model, housed within the ReaderBench platform. CNA, grounded in theories of cohesion, dialogism, and polyphony, is similar to social network analysis (SNA), but it also considers text content and discourse structure and, uniquely, uses automated cohesion indices to generate the underlying discourse representation. Thus, CNA enhances the power of SNA by explicitly considering semantic cohesion while modeling interactions between participants. The primary purpose of this article is to describe CNA analysis and to provide a proof of concept, by using ten chat conversations in which multiple participants debated the advantages of CSCL technologies. Each participant's contributions were human-scored on the basis of their relevance in terms of covering the central concepts of the conversation. SNA metrics, applied to the CNA sociogram, were then used to assess the quality of each member's degree of participation. The results revealed that the CNA indices were strongly correlated to the human evaluations of the conversations. Furthermore, a stepwise regression analysis indicated that the CNA indices collectively predicted 54% of the variance in the human ratings of participation. The results provide promising support for the use of automated computational assessments of collaborative participation and of individuals' degrees of active involvement in CSCL environments.

  11. Understanding Classrooms through Social Network Analysis: A Primer for Social Network Analysis in Education Research (United States)

    Grunspan, Daniel Z.; Wiggins, Benjamin L.; Goodreau, Steven M.


    Social interactions between students are a major and underexplored part of undergraduate education. Understanding how learning relationships form in undergraduate classrooms, as well as the impacts these relationships have on learning outcomes, can inform educators in unique ways and improve educational reform. Social network analysis (SNA)…

  12. Network motif-based identification of transcription factor-target gene relationships by integrating multi-source biological data

    Directory of Open Access Journals (Sweden)

    de los Reyes Benildo G


    Full Text Available Abstract Background Integrating data from multiple global assays and curated databases is essential to understand the spatio-temporal interactions within cells. Different experiments measure cellular processes at various widths and depths, while databases contain biological information based on established facts or published data. Integrating these complementary datasets helps infer a mutually consistent transcriptional regulatory network (TRN with strong similarity to the structure of the underlying genetic regulatory modules. Decomposing the TRN into a small set of recurring regulatory patterns, called network motifs (NM, facilitates the inference. Identifying NMs defined by specific transcription factors (TF establishes the framework structure of a TRN and allows the inference of TF-target gene relationship. This paper introduces a computational framework for utilizing data from multiple sources to infer TF-target gene relationships on the basis of NMs. The data include time course gene expression profiles, genome-wide location analysis data, binding sequence data, and gene ontology (GO information. Results The proposed computational framework was tested using gene expression data associated with cell cycle progression in yeast. Among 800 cell cycle related genes, 85 were identified as candidate TFs and classified into four previously defined NMs. The NMs for a subset of TFs are obtained from literature. Support vector machine (SVM classifiers were used to estimate NMs for the remaining TFs. The potential downstream target genes for the TFs were clustered into 34 biologically significant groups. The relationships between TFs and potential target gene clusters were examined by training recurrent neural networks whose topologies mimic the NMs to which the TFs are classified. The identified relationships between TFs and gene clusters were evaluated using the following biological validation and statistical analyses: (1 Gene set enrichment

  13. Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective. (United States)

    Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco


    The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. Copyright © 2016 the American Physiological Society.

  14. Analysis and monitoring design for networks

    Energy Technology Data Exchange (ETDEWEB)

    Fedorov, V.; Flanagan, D.; Rowan, T.; Batsell, S.


    The idea of applying experimental design methodologies to develop monitoring systems for computer networks is relatively novel even though it was applied in other areas such as meteorology, seismology, and transportation. One objective of a monitoring system should always be to collect as little data as necessary to be able to monitor specific parameters of the system with respect to assigned targets and objectives. This implies a purposeful monitoring where each piece of data has a reason to be collected and stored for future use. When a computer network system as large and complex as the Internet is the monitoring subject, providing an optimal and parsimonious observing system becomes even more important. Many data collection decisions must be made by the developers of a monitoring system. These decisions include but are not limited to the following: (1) The type data collection hardware and software instruments to be used; (2) How to minimize interruption of regular network activities during data collection; (3) Quantification of the objectives and the formulation of optimality criteria; (4) The placement of data collection hardware and software devices; (5) The amount of data to be collected in a given time period, how large a subset of the available data to collect during the period, the length of the period, and the frequency of data collection; (6) The determination of the data to be collected (for instance, selection of response and explanatory variables); (7) Which data will be retained and how long (i.e., data storage and retention issues); and (8) The cost analysis of experiments. Mathematical statistics, and, in particular, optimal experimental design methods, may be used to address the majority of problems generated by 3--7. In this study, the authors focus their efforts on topics 3--5.

  15. Modeling a Complex Biological Network with Temporal Heterogeneity: Cardiac Myocyte Plasticity as a Case Study (United States)

    Mazloom, Amin R.; Basu, Kalyan; Mandal, Subhrangsu S.; Das, Sajal K.

    Complex biological systems often characterize nonlinear dynamics. Employing traditional deterministic or stochastic approaches to quantify these dynamics either fail to capture their existing deviant effects or lead to combinatorial explosion. In this work we devised a novel approach that projects the biological functions within a pathway to a network of stochastic events that are random in time and space. By applying this approach recursively to the object system we build the event network of the entire system. The dynamics of the system evolves through the execution of the event network by a simulation engine which comprised of a time prioritized event queue. As a case study we utilized the current method and conducted an in-silico experiment on the metabolic plasticity of a cardiac myocyete. We aimed to quantify the down stream effects of insulin signaling that predominantly controls the plasticity in myocardium. Intriguingly, our in-silico results on transcription regulatory effect of insulin showed a good agreement with experimental data. Meanwhile we were able to characterize the flux change across major metabolic pathways over 48 hours of the in-silico experiment. Our simulation performed a remarkable efficiency by conducting 48 hours of simulation-time in less that 2 hours of processor time.

  16. An Error Analysis of Structured Light Scanning of Biological Tissue

    DEFF Research Database (Denmark)

    Jensen, Sebastian Hoppe Nesgaard; Wilm, Jakob; Aanæs, Henrik


    This paper presents an error analysis and correction model for four structured light methods applied to three common types of biological tissue; skin, fat and muscle. Despite its many advantages, structured light is based on the assumption of direct reflection at the object surface only....... This assumption is violated by most biological material e.g. human skin, which exhibits subsurface scattering. In this study, we find that in general, structured light scans of biological tissue deviate significantly from the ground truth. We show that a large portion of this error can be predicted with a simple......, statistical linear model based on the scan geometry. As such, scans can be corrected without introducing any specially designed pattern strategy or hardware. We can effectively reduce the error in a structured light scanner applied to biological tissue by as much as factor of two or three....

  17. 6th International Conference on Network Analysis

    CERN Document Server

    Nikolaev, Alexey; Pardalos, Panos; Prokopyev, Oleg


    This valuable source for graduate students and researchers provides a comprehensive introduction to current theories and applications in optimization methods and network models. Contributions to this book are focused on new efficient algorithms and rigorous mathematical theories, which can be used to optimize and analyze mathematical graph structures with massive size and high density induced by natural or artificial complex networks. Applications to social networks, power transmission grids, telecommunication networks, stock market networks, and human brain networks are presented. Chapters in this book cover the following topics: Linear max min fairness Heuristic approaches for high-quality solutions Efficient approaches for complex multi-criteria optimization problems Comparison of heuristic algorithms New heuristic iterative local search Power in network structures Clustering nodes in random graphs Power transmission grid structure Network decomposition problems Homogeneity hypothesis testing Network analy...

  18. New Markov-autocorrelation indices for re-evaluation of links in chemical and biological complex networks used in metabolomics, parasitology, neurosciences, and epidemiology. (United States)

    González-Díaz, Humberto; Riera-Fernández, Pablo


    The development of new methods for the computational re-evaluation of links in chemical and biological complex networks is very important to save time and resources. The Moreau-Broto autocorrelation indices (MBis) are well-known topological indices (TIs) used in QSAR/QSPR studies to encode the structural information contained in molecular graphs. In addition, MBis and similar autocorrelation measures have been used to study other systems like, for example, proteins. In the present work, MBis are combined with Markov chains to develop a general class of stochastic MBis of order k (MB(k)) that is used to encode the structural information contained in different types of large complex networks. The MB(k) values obtained for the nodes (centralities) of these networks are used as input variables to seek QSPR-like equations (by means of linear discriminant analysis) in which the outputs are numerical scores S(L(ij)) that allow us to discriminate between connected and nonconnected nodes and therefore re-evaluate the connectivity of the whole network. The models developed in this work produced the following results in terms of overall accuracy for network reconstruction: metabolic networks (72.10%), parasite-host networks (88.70%), CoCoMac brain cortex coactivation network (81.89%), and fasciolosis spreading network (86.39%).

  19. Artificial neural network for violation analysis

    International Nuclear Information System (INIS)

    Zhang, Z.; Polet, P.; Vanderhaegen, F.; Millot, P.


    Barrier removal (BR) is a safety-related violation, and it can be analyzed in terms of benefits, costs, and potential deficits. In order to allow designers to integrate BR into the risk analysis during the initial design phase or during re-design work, we propose a connectionist method integrating self-organizing maps (SOM). The basic SOM is an artificial neural network that, on the basis of the information contained in a multi-dimensional space, generates a space of lesser dimensions. Three algorithms--Unsupervised SOM, Supervised SOM, and Hierarchical SOM--have been developed to permit BR classification and prediction in terms of the different criteria. The proposed method can be used, on the one hand, to foresee/predict the possibility level of a new/changed barrier (prospective analysis), and on the other hand, to synthetically regroup/rearrange the BR of a given human-machine system (retrospective analysis). We applied this method to the BR analysis of an experimental railway simulator, and our preliminary results are presented here

  20. Dynamic analysis of biochemical network using complex network method

    Directory of Open Access Journals (Sweden)

    Wang Shuqiang


    Full Text Available In this study, the stochastic biochemical reaction model is proposed based on the law of mass action and complex network theory. The dynamics of biochemical reaction system is presented as a set of non-linear differential equations and analyzed at the molecular-scale. Given the initial state and the evolution rules of the biochemical reaction system, the system can achieve homeostasis. Compared with random graph, the biochemical reaction network has larger information capacity and is more efficient in information transmission. This is consistent with theory of evolution.

  1. Interactive analysis of systems biology molecular expression data

    Directory of Open Access Journals (Sweden)

    Prabhakar Sunil


    Full Text Available Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe in growth media (an ionomics dataset. This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology.

  2. Network reliability analysis based on percolation theory

    International Nuclear Information System (INIS)

    Li, Daqing; Zhang, Qiong; Zio, Enrico; Havlin, Shlomo; Kang, Rui


    In this paper, we propose a new way of looking at the reliability of a network using percolation theory. In this new view, a network failure can be regarded as a percolation process and the critical threshold of percolation can be used as network failure criterion linked to the operational settings under control. To demonstrate our approach, we consider both random network models and real networks with different nodes and/or edges lifetime distributions. We study numerically and theoretically the network reliability and find that the network reliability can be solved as a voting system with threshold given by percolation theory. Then we find that the average lifetime of random network increases linearly with the average lifetime of its nodes with uniform life distributions. Furthermore, the average lifetime of the network becomes saturated when system size is increased. Finally, we demonstrate our method on the transmission network system of IEEE 14 bus. - Highlights: • Based on percolation theory, we address questions of practical interest such as “how many failed nodes/edges will break down the whole network?” • The percolation threshold naturally gives a network failure criterion. • The approach based on percolation theory is suited for calculations of large-scale networks

  3. Analysis of robustness of urban bus network (United States)

    Tao, Ren; Yi-Fan, Wang; Miao-Miao, Liu; Yan-Jie, Xu


    In this paper, the invulnerabi