WorldWideScience

Sample records for protein network evolution

  1. Interplay between chaperones and protein disorder promotes the evolution of protein networks.

    Directory of Open Access Journals (Sweden)

    Sebastian Pechmann

    2014-06-01

    Full Text Available Evolution is driven by mutations, which lead to new protein functions but come at a cost to protein stability. Non-conservative substitutions are of interest in this regard because they may most profoundly affect both function and stability. Accordingly, organisms must balance the benefit of accepting advantageous substitutions with the possible cost of deleterious effects on protein folding and stability. We here examine factors that systematically promote non-conservative mutations at the proteome level. Intrinsically disordered regions in proteins play pivotal roles in protein interactions, but many questions regarding their evolution remain unanswered. Similarly, whether and how molecular chaperones, which have been shown to buffer destabilizing mutations in individual proteins, generally provide robustness during proteome evolution remains unclear. To this end, we introduce an evolutionary parameter λ that directly estimates the rate of non-conservative substitutions. Our analysis of λ in Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens sequences reveals how co- and post-translationally acting chaperones differentially promote non-conservative substitutions in their substrates, likely through buffering of their destabilizing effects. We further find that λ serves well to quantify the evolution of intrinsically disordered proteins even though the unstructured, thus generally variable regions in proteins are often flanked by very conserved sequences. Crucially, we show that both intrinsically disordered proteins and highly re-wired proteins in protein interaction networks, which have evolved new interactions and functions, exhibit a higher λ at the expense of enhanced chaperone assistance. Our findings thus highlight an intricate interplay of molecular chaperones and protein disorder in the evolvability of protein networks. Our results illuminate the role of chaperones in enabling protein evolution, and underline the

  2. Evolution of a protein domain interaction network

    International Nuclear Information System (INIS)

    Li-Feng, Gao; Jian-Jun, Shi; Shan, Guan

    2010-01-01

    In this paper, we attempt to understand complex network evolution from the underlying evolutionary relationship between biological organisms. Firstly, we construct a Pfam domain interaction network for each of the 470 completely sequenced organisms, and therefore each organism is correlated with a specific Pfam domain interaction network; secondly, we infer the evolutionary relationship of these organisms with the nearest neighbour joining method; thirdly, we use the evolutionary relationship between organisms constructed in the second step as the evolutionary course of the Pfam domain interaction network constructed in the first step. This analysis of the evolutionary course shows: (i) there is a conserved sub-network structure in network evolution; in this sub-network, nodes with lower degree prefer to maintain their connectivity invariant, and hubs tend to maintain their role as a hub is attached preferentially to new added nodes; (ii) few nodes are conserved as hubs; most of the other nodes are conserved as one with very low degree; (iii) in the course of network evolution, new nodes are added to the network either individually in most cases or as clusters with relative high clustering coefficients in a very few cases. (general)

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

    Directory of Open Access Journals (Sweden)

    Guo Hao

    2011-05-01

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

  4. Evolution of a G protein-coupled receptor response by mutations in regulatory network interactions

    DEFF Research Database (Denmark)

    Di Roberto, Raphaël B; Chang, Belinda; Trusina, Ala

    2016-01-01

    All cellular functions depend on the concerted action of multiple proteins organized in complex networks. To understand how selection acts on protein networks, we used the yeast mating receptor Ste2, a pheromone-activated G protein-coupled receptor, as a model system. In Saccharomyces cerevisiae......, Ste2 is a hub in a network of interactions controlling both signal transduction and signal suppression. Through laboratory evolution, we obtained 21 mutant receptors sensitive to the pheromone of a related yeast species and investigated the molecular mechanisms behind this newfound sensitivity. While...... demonstrate that a new receptor-ligand pair can evolve through network-altering mutations independently of receptor-ligand binding, and suggest a potential role for such mutations in disease....

  5. Pleiotropy constrains the evolution of protein but not regulatory sequences in a transcription regulatory network influencing complex social behaviours

    Directory of Open Access Journals (Sweden)

    Daria eMolodtsova

    2014-12-01

    Full Text Available It is increasingly apparent that genes and networks that influence complex behaviour are evolutionary conserved, which is paradoxical considering that behaviour is labile over evolutionary timescales. How does adaptive change in behaviour arise if behaviour is controlled by conserved, pleiotropic, and likely evolutionary constrained genes? Pleiotropy and connectedness are known to constrain the general rate of protein evolution, prompting some to suggest that the evolution of complex traits, including behaviour, is fuelled by regulatory sequence evolution. However, we seldom have data on the strength of selection on mutations in coding and regulatory sequences, and this hinders our ability to study how pleiotropy influences coding and regulatory sequence evolution. Here we use population genomics to estimate the strength of selection on coding and regulatory mutations for a transcriptional regulatory network that influences complex behaviour of honey bees. We found that replacement mutations in highly connected transcription factors and target genes experience significantly stronger negative selection relative to weakly connected transcription factors and targets. Adaptively evolving proteins were significantly more likely to reside at the periphery of the regulatory network, while proteins with signs of negative selection were near the core of the network. Interestingly, connectedness and network structure had minimal influence on the strength of selection on putative regulatory sequences for both transcription factors and their targets. Our study indicates that adaptive evolution of complex behaviour can arise because of positive selection on protein-coding mutations in peripheral genes, and on regulatory sequence mutations in both transcription factors and their targets throughout the network.

  6. Emergence of modularity and disassortativity in protein-protein interaction networks.

    Science.gov (United States)

    Wan, Xi; Cai, Shuiming; Zhou, Jin; Liu, Zengrong

    2010-12-01

    In this paper, we present a simple evolution model of protein-protein interaction networks by introducing a rule of small-preference duplication of a node, meaning that the probability of a node chosen to duplicate is inversely proportional to its degree, and subsequent divergence plus nonuniform heterodimerization based on some plausible mechanisms in biology. We show that our model cannot only reproduce scale-free connectivity and small-world pattern, but also exhibit hierarchical modularity and disassortativity. After comparing the features of our model with those of real protein-protein interaction networks, we believe that our model can provide relevant insights into the mechanism underlying the evolution of protein-protein interaction networks. © 2010 American Institute of Physics.

  7. Protein-protein interaction network-based detection of functionally similar proteins within species.

    Science.gov (United States)

    Song, Baoxing; Wang, Fen; Guo, Yang; Sang, Qing; Liu, Min; Li, Dengyun; Fang, Wei; Zhang, Deli

    2012-07-01

    Although functionally similar proteins across species have been widely studied, functionally similar proteins within species showing low sequence similarity have not been examined in detail. Identification of these proteins is of significant importance for understanding biological functions, evolution of protein families, progression of co-evolution, and convergent evolution and others which cannot be obtained by detection of functionally similar proteins across species. Here, we explored a method of detecting functionally similar proteins within species based on graph theory. After denoting protein-protein interaction networks using graphs, we split the graphs into subgraphs using the 1-hop method. Proteins with functional similarities in a species were detected using a method of modified shortest path to compare these subgraphs and to find the eligible optimal results. Using seven protein-protein interaction networks and this method, some functionally similar proteins with low sequence similarity that cannot detected by sequence alignment were identified. By analyzing the results, we found that, sometimes, it is difficult to separate homologous from convergent evolution. Evaluation of the performance of our method by gene ontology term overlap showed that the precision of our method was excellent. Copyright © 2012 Wiley Periodicals, Inc.

  8. Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

    Science.gov (United States)

    Garamszegi, Sara; Franzosa, Eric A; Xia, Yu

    2013-01-01

    A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are

  9. Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Sara Garamszegi

    Full Text Available A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1 domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2 domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral

  10. Network evolution: rewiring and signatures of conservation in signaling.

    Directory of Open Access Journals (Sweden)

    Mark G F Sun

    Full Text Available The analysis of network evolution has been hampered by limited availability of protein interaction data for different organisms. In this study, we investigate evolutionary mechanisms in Src Homology 3 (SH3 domain and kinase interaction networks using high-resolution specificity profiles. We constructed and examined networks for 23 fungal species ranging from Saccharomyces cerevisiae to Schizosaccharomyces pombe. We quantify rates of different rewiring mechanisms and show that interaction change through binding site evolution is faster than through gene gain or loss. We found that SH3 interactions evolve swiftly, at rates similar to those found in phosphoregulation evolution. Importantly, we show that interaction changes are sufficiently rapid to exhibit saturation phenomena at the observed timescales. Finally, focusing on the SH3 interaction network, we observe extensive clustering of binding sites on target proteins by SH3 domains and a strong correlation between the number of domains that bind a target protein (target in-degree and interaction conservation. The relationship between in-degree and interaction conservation is driven by two different effects, namely the number of clusters that correspond to interaction interfaces and the number of domains that bind to each cluster leads to sequence specific conservation, which in turn results in interaction conservation. In summary, we uncover several network evolution mechanisms likely to generalize across peptide recognition modules.

  11. The architectural design of networks of protein domain architectures.

    Science.gov (United States)

    Hsu, Chia-Hsin; Chen, Chien-Kuo; Hwang, Ming-Jing

    2013-08-23

    Protein domain architectures (PDAs), in which single domains are linked to form multiple-domain proteins, are a major molecular form used by evolution for the diversification of protein functions. However, the design principles of PDAs remain largely uninvestigated. In this study, we constructed networks to connect domain architectures that had grown out from the same single domain for every single domain in the Pfam-A database and found that there are three main distinctive types of these networks, which suggests that evolution can exploit PDAs in three different ways. Further analysis showed that these three different types of PDA networks are each adopted by different types of protein domains, although many networks exhibit the characteristics of more than one of the three types. Our results shed light on nature's blueprint for protein architecture and provide a framework for understanding architectural design from a network perspective.

  12. Modular co-evolution of metabolic networks

    Directory of Open Access Journals (Sweden)

    Yu Zhong-Hao

    2007-08-01

    Full Text Available Abstract Background The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear. Results In this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do. Conclusion The correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome-scale network context, giving a novel perspective on molecular evolution.

  13. Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes.

    Science.gov (United States)

    Nillegoda, Nadinath B; Stank, Antonia; Malinverni, Duccio; Alberts, Niels; Szlachcic, Anna; Barducci, Alessandro; De Los Rios, Paolo; Wade, Rebecca C; Bukau, Bernd

    2017-05-15

    Hsp70 participates in a broad spectrum of protein folding processes extending from nascent chain folding to protein disaggregation. This versatility in function is achieved through a diverse family of J-protein cochaperones that select substrates for Hsp70. Substrate selection is further tuned by transient complexation between different classes of J-proteins, which expands the range of protein aggregates targeted by metazoan Hsp70 for disaggregation. We assessed the prevalence and evolutionary conservation of J-protein complexation and cooperation in disaggregation. We find the emergence of a eukaryote-specific signature for interclass complexation of canonical J-proteins. Consistently, complexes exist in yeast and human cells, but not in bacteria, and correlate with cooperative action in disaggregation in vitro. Signature alterations exclude some J-proteins from networking, which ensures correct J-protein pairing, functional network integrity and J-protein specialization. This fundamental change in J-protein biology during the prokaryote-to-eukaryote transition allows for increased fine-tuning and broadening of Hsp70 function in eukaryotes.

  14. In silico modeling of the yeast protein and protein family interaction network

    Science.gov (United States)

    Goh, K.-I.; Kahng, B.; Kim, D.

    2004-03-01

    Understanding of how protein interaction networks of living organisms have evolved or are organized can be the first stepping stone in unveiling how life works on a fundamental ground. Here we introduce an in silico ``coevolutionary'' model for the protein interaction network and the protein family network. The essential ingredient of the model includes the protein family identity and its robustness under evolution, as well as the three previously proposed: gene duplication, divergence, and mutation. This model produces a prototypical feature of complex networks in a wide range of parameter space, following the generalized Pareto distribution in connectivity. Moreover, we investigate other structural properties of our model in detail with some specific values of parameters relevant to the yeast Saccharomyces cerevisiae, showing excellent agreement with the empirical data. Our model indicates that the physical constraints encoded via the domain structure of proteins play a crucial role in protein interactions.

  15. Evolution of SH2 domains and phosphotyrosine signalling networks

    Science.gov (United States)

    Liu, Bernard A.; Nash, Piers D.

    2012-01-01

    Src homology 2 (SH2) domains mediate selective protein–protein interactions with tyrosine phosphorylated proteins, and in doing so define specificity of phosphotyrosine (pTyr) signalling networks. SH2 domains and protein-tyrosine phosphatases expand alongside protein-tyrosine kinases (PTKs) to coordinate cellular and organismal complexity in the evolution of the unikont branch of the eukaryotes. Examination of conserved families of PTKs and SH2 domain proteins provides fiduciary marks that trace the evolutionary landscape for the development of complex cellular systems in the proto-metazoan and metazoan lineages. The evolutionary provenance of conserved SH2 and PTK families reveals the mechanisms by which diversity is achieved through adaptations in tissue-specific gene transcription, altered ligand binding, insertions of linear motifs and the gain or loss of domains following gene duplication. We discuss mechanisms by which pTyr-mediated signalling networks evolve through the development of novel and expanded families of SH2 domain proteins and the elaboration of connections between pTyr-signalling proteins. These changes underlie the variety of general and specific signalling networks that give rise to tissue-specific functions and increasingly complex developmental programmes. Examination of SH2 domains from an evolutionary perspective provides insight into the process by which evolutionary expansion and modification of molecular protein interaction domain proteins permits the development of novel protein-interaction networks and accommodates adaptation of signalling networks. PMID:22889907

  16. Evolution favors protein mutational robustness in sufficiently large populations

    Directory of Open Access Journals (Sweden)

    Venturelli Ophelia S

    2007-07-01

    Full Text Available Abstract Background An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. Results Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by mathematical theory, and can be quantitatively related to the way that the proteins occupy their neutral network. Conclusion Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon could contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations.

  17. Completing sparse and disconnected protein-protein network by deep learning.

    Science.gov (United States)

    Huang, Lei; Liao, Li; Wu, Cathy H

    2018-03-22

    Protein-protein interaction (PPI) prediction remains a central task in systems biology to achieve a better and holistic understanding of cellular and intracellular processes. Recently, an increasing number of computational methods have shifted from pair-wise prediction to network level prediction. Many of the existing network level methods predict PPIs under the assumption that the training network should be connected. However, this assumption greatly affects the prediction power and limits the application area because the current golden standard PPI networks are usually very sparse and disconnected. Therefore, how to effectively predict PPIs based on a training network that is sparse and disconnected remains a challenge. In this work, we developed a novel PPI prediction method based on deep learning neural network and regularized Laplacian kernel. We use a neural network with an autoencoder-like architecture to implicitly simulate the evolutionary processes of a PPI network. Neurons of the output layer correspond to proteins and are labeled with values (1 for interaction and 0 for otherwise) from the adjacency matrix of a sparse disconnected training PPI network. Unlike autoencoder, neurons at the input layer are given all zero input, reflecting an assumption of no a priori knowledge about PPIs, and hidden layers of smaller sizes mimic ancient interactome at different times during evolution. After the training step, an evolved PPI network whose rows are outputs of the neural network can be obtained. We then predict PPIs by applying the regularized Laplacian kernel to the transition matrix that is built upon the evolved PPI network. The results from cross-validation experiments show that the PPI prediction accuracies for yeast data and human data measured as AUC are increased by up to 8.4 and 14.9% respectively, as compared to the baseline. Moreover, the evolved PPI network can also help us leverage complementary information from the disconnected training network

  18. Protein sequence comparison and protein evolution

    Energy Technology Data Exchange (ETDEWEB)

    Pearson, W.R. [Univ. of Virginia, Charlottesville, VA (United States). Dept. of Biochemistry

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. This tutorial examines how the information conserved during the evolution of a protein molecule can be used to infer reliably homology, and thus a shared proteinfold and possibly a shared active site or function. The authors start by reviewing a geological/evolutionary time scale. Next they look at the evolution of several protein families. During the tutorial, these families will be used to demonstrate that homologous protein ancestry can be inferred with confidence. They also examine different modes of protein evolution and consider some hypotheses that have been presented to explain the very earliest events in protein evolution. The next part of the tutorial will examine the technical aspects of protein sequence comparison. Both optimal and heuristic algorithms and their associated parameters that are used to characterize protein sequence similarities are discussed. Perhaps more importantly, they survey the statistics of local similarity scores, and how these statistics can both be used to improve the selectivity of a search and to evaluate the significance of a match. They them examine distantly related members of three protein families, the serine proteases, the glutathione transferases, and the G-protein-coupled receptors (GCRs). Finally, the discuss how sequence similarity can be used to examine internal repeated or mosaic structures in proteins.

  19. DETECTION OF TOPOLOGICAL PATTERNS IN PROTEIN NETWORKS.

    Energy Technology Data Exchange (ETDEWEB)

    MASLOV,S.SNEPPEN,K.

    2003-11-17

    interesting property of many biological networks that was recently brought to attention of the scientific community [3, 4, 5] is an extremely broad distribution of node connectivities defined as the number of immediate neighbors of a given node in the network. While the majority of nodes have just a few edges connecting them to other nodes in the network, there exist some nodes, that we will refer to as ''hubs'', with an unusually large number of neighbors. The connectivity of the most connected hub in such a network is typically several orders of magnitude larger than the average connectivity in the network. Often the distribution of connectivities of individual nodes can be approximated by a scale-free power law form [3] in which case the network is referred to as scale-free. Among biological networks distributions of node connectivities in metabolic [4], protein interaction [5], and brain functional [6] networks can be reasonably approximated by a power law extending for several orders of magnitude. The set of connectivities of individual nodes is an example of a low-level (single-node) topological property of a network. While it answers the question about how many neighbors a given node has, it gives no information about the identity of those neighbors. It is clear that most functional properties of networks are defined at a higher topological level in the exact pattern of connections of nodes to each other. However, such multi-node connectivity patterns are rather difficult to quantify and compare between networks. In this work we concentrate on multi-node topological properties of protein networks. These networks (as any other biological networks) lack the top-down design. Instead, selective forces of biological evolution shape them from raw material provided by random events such as mutations within individual genes, and gene duplications. As a result their connections are characterized by a large degree of randomness. One may wonder which

  20. Specificity and evolvability in eukaryotic protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Pedro Beltrao

    2007-02-01

    Full Text Available Progress in uncovering the protein interaction networks of several species has led to questions of what underlying principles might govern their organization. Few studies have tried to determine the impact of protein interaction network evolution on the observed physiological differences between species. Using comparative genomics and structural information, we show here that eukaryotic species have rewired their interactomes at a fast rate of approximately 10(-5 interactions changed per protein pair, per million years of divergence. For Homo sapiens this corresponds to 10(3 interactions changed per million years. Additionally we find that the specificity of binding strongly determines the interaction turnover and that different biological processes show significantly different link dynamics. In particular, human proteins involved in immune response, transport, and establishment of localization show signs of positive selection for change of interactions. Our analysis suggests that a small degree of molecular divergence can give rise to important changes at the network level. We propose that the power law distribution observed in protein interaction networks could be partly explained by the cell's requirement for different degrees of protein binding specificity.

  1. A conserved mammalian protein interaction network.

    Directory of Open Access Journals (Sweden)

    Åsa Pérez-Bercoff

    Full Text Available Physical interactions between proteins mediate a variety of biological functions, including signal transduction, physical structuring of the cell and regulation. While extensive catalogs of such interactions are known from model organisms, their evolutionary histories are difficult to study given the lack of interaction data from phylogenetic outgroups. Using phylogenomic approaches, we infer a upper bound on the time of origin for a large set of human protein-protein interactions, showing that most such interactions appear relatively ancient, dating no later than the radiation of placental mammals. By analyzing paired alignments of orthologous and putatively interacting protein-coding genes from eight mammals, we find evidence for weak but significant co-evolution, as measured by relative selective constraint, between pairs of genes with interacting proteins. However, we find no strong evidence for shared instances of directional selection within an interacting pair. Finally, we use a network approach to show that the distribution of selective constraint across the protein interaction network is non-random, with a clear tendency for interacting proteins to share similar selective constraints. Collectively, the results suggest that, on the whole, protein interactions in mammals are under selective constraint, presumably due to their functional roles.

  2. Cross-linked structure of network evolution

    International Nuclear Information System (INIS)

    Bassett, Danielle S.; Wymbs, Nicholas F.; Grafton, Scott T.; Porter, Mason A.; Mucha, Peter J.

    2014-01-01

    We study the temporal co-variation of network co-evolution via the cross-link structure of networks, for which we take advantage of the formalism of hypergraphs to map cross-link structures back to network nodes. We investigate two sets of temporal network data in detail. In a network of coupled nonlinear oscillators, hyperedges that consist of network edges with temporally co-varying weights uncover the driving co-evolution patterns of edge weight dynamics both within and between oscillator communities. In the human brain, networks that represent temporal changes in brain activity during learning exhibit early co-evolution that then settles down with practice. Subsequent decreases in hyperedge size are consistent with emergence of an autonomous subgraph whose dynamics no longer depends on other parts of the network. Our results on real and synthetic networks give a poignant demonstration of the ability of cross-link structure to uncover unexpected co-evolution attributes in both real and synthetic dynamical systems. This, in turn, illustrates the utility of analyzing cross-links for investigating the structure of temporal networks

  3. Cross-linked structure of network evolution

    Energy Technology Data Exchange (ETDEWEB)

    Bassett, Danielle S., E-mail: dsb@seas.upenn.edu [Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Department of Physics, University of California, Santa Barbara, California 93106 (United States); Sage Center for the Study of the Mind, University of California, Santa Barbara, California 93106 (United States); Wymbs, Nicholas F.; Grafton, Scott T. [Department of Psychology and UCSB Brain Imaging Center, University of California, Santa Barbara, California 93106 (United States); Porter, Mason A. [Oxford Centre for Industrial and Applied Mathematics, Mathematical Institute, University of Oxford, Oxford OX2 6GG (United Kingdom); CABDyN Complexity Centre, University of Oxford, Oxford, OX1 1HP (United Kingdom); Mucha, Peter J. [Carolina Center for Interdisciplinary Applied Mathematics, Department of Mathematics, University of North Carolina, Chapel Hill, North Carolina 27599 (United States); Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)

    2014-03-15

    We study the temporal co-variation of network co-evolution via the cross-link structure of networks, for which we take advantage of the formalism of hypergraphs to map cross-link structures back to network nodes. We investigate two sets of temporal network data in detail. In a network of coupled nonlinear oscillators, hyperedges that consist of network edges with temporally co-varying weights uncover the driving co-evolution patterns of edge weight dynamics both within and between oscillator communities. In the human brain, networks that represent temporal changes in brain activity during learning exhibit early co-evolution that then settles down with practice. Subsequent decreases in hyperedge size are consistent with emergence of an autonomous subgraph whose dynamics no longer depends on other parts of the network. Our results on real and synthetic networks give a poignant demonstration of the ability of cross-link structure to uncover unexpected co-evolution attributes in both real and synthetic dynamical systems. This, in turn, illustrates the utility of analyzing cross-links for investigating the structure of temporal networks.

  4. Protein-Protein Interaction Network and Gene Ontology

    Science.gov (United States)

    Choi, Yunkyu; Kim, Seok; Yi, Gwan-Su; Park, Jinah

    Evolution of computer technologies makes it possible to access a large amount and various kinds of biological data via internet such as DNA sequences, proteomics data and information discovered about them. It is expected that the combination of various data could help researchers find further knowledge about them. Roles of a visualization system are to invoke human abilities to integrate information and to recognize certain patterns in the data. Thus, when the various kinds of data are examined and analyzed manually, an effective visualization system is an essential part. One instance of these integrated visualizations can be combination of protein-protein interaction (PPI) data and Gene Ontology (GO) which could help enhance the analysis of PPI network. We introduce a simple but comprehensive visualization system that integrates GO and PPI data where GO and PPI graphs are visualized side-by-side and supports quick reference functions between them. Furthermore, the proposed system provides several interactive visualization methods for efficiently analyzing the PPI network and GO directedacyclic- graph such as context-based browsing and common ancestors finding.

  5. Convergent evolution and mimicry of protein linear motifs in host-pathogen interactions.

    Science.gov (United States)

    Chemes, Lucía Beatriz; de Prat-Gay, Gonzalo; Sánchez, Ignacio Enrique

    2015-06-01

    Pathogen linear motif mimics are highly evolvable elements that facilitate rewiring of host protein interaction networks. Host linear motifs and pathogen mimics differ in sequence, leading to thermodynamic and structural differences in the resulting protein-protein interactions. Moreover, the functional output of a mimic depends on the motif and domain repertoire of the pathogen protein. Regulatory evolution mediated by linear motifs can be understood by measuring evolutionary rates, quantifying positive and negative selection and performing phylogenetic reconstructions of linear motif natural history. Convergent evolution of linear motif mimics is widespread among unrelated proteins from viral, prokaryotic and eukaryotic pathogens and can also take place within individual protein phylogenies. Statistics, biochemistry and laboratory models of infection link pathogen linear motifs to phenotypic traits such as tropism, virulence and oncogenicity. In vitro evolution experiments and analysis of natural sequences suggest that changes in linear motif composition underlie pathogen adaptation to a changing environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Biophysics of protein evolution and evolutionary protein biophysics

    Science.gov (United States)

    Sikosek, Tobias; Chan, Hue Sun

    2014-01-01

    The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence–structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by ‘hidden’ conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution. PMID:25165599

  7. Evolution of protein-protein interactions

    Indian Academy of Sciences (India)

    Evolution of protein-protein interactions · Our interests in protein-protein interactions · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20.

  8. Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.

    Science.gov (United States)

    Amoutzias, Gregory D; Robertson, David L; Oliver, Stephen G; Bornberg-Bauer, Erich

    2004-03-01

    By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix-loop-helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks emerging through single-gene duplications, the dominant importance of molecular modularity in the bottom-up construction of complex biological entities, and the convergent evolution of networks.

  9. Evolution of Linux operating system network

    Science.gov (United States)

    Xiao, Guanping; Zheng, Zheng; Wang, Haoqin

    2017-01-01

    Linux operating system (LOS) is a sophisticated man-made system and one of the most ubiquitous operating systems. However, there is little research on the structure and functionality evolution of LOS from the prospective of networks. In this paper, we investigate the evolution of the LOS network. 62 major releases of LOS ranging from versions 1.0 to 4.1 are modeled as directed networks in which functions are denoted by nodes and function calls are denoted by edges. It is found that the size of the LOS network grows almost linearly, while clustering coefficient monotonically decays. The degree distributions are almost the same: the out-degree follows an exponential distribution while both in-degree and undirected degree follow power-law distributions. We further explore the functionality evolution of the LOS network. It is observed that the evolution of functional modules is shown as a sequence of seven events (changes) succeeding each other, including continuing, growth, contraction, birth, splitting, death and merging events. By means of a statistical analysis of these events in the top 4 largest components (i.e., arch, drivers, fs and net), it is shown that continuing, growth and contraction events occupy more than 95% events. Our work exemplifies a better understanding and describing of the dynamics of LOS evolution.

  10. A random network based, node attraction facilitated network evolution method

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2016-03-01

    Full Text Available In present study, I present a method of network evolution that based on random network, and facilitated by node attraction. In this method, I assume that the initial network is a random network, or a given initial network. When a node is ready to connect, it tends to link to the node already owning the most connections, which coincides with the general rule (Barabasi and Albert, 1999 of node connecting. In addition, a node may randomly disconnect a connection i.e., the addition of connections in the network is accompanied by the pruning of some connections. The dynamics of network evolution is determined of the attraction factor Lamda of nodes, the probability of node connection, the probability of node disconnection, and the expected initial connectance. The attraction factor of nodes, the probability of node connection, and the probability of node disconnection are time and node varying. Various dynamics can be achieved by adjusting these parameters. Effects of simplified parameters on network evolution are analyzed. The changes of attraction factor Lamda can reflect various effects of the node degree on connection mechanism. Even the changes of Lamda only will generate various networks from the random to the complex. Therefore, the present algorithm can be treated as a general model for network evolution. Modeling results show that to generate a power-law type of network, the likelihood of a node attracting connections is dependent upon the power function of the node's degree with a higher-order power. Matlab codes for simplified version of the method are provided.

  11. Opinion evolution in different social acquaintance networks

    Science.gov (United States)

    Chen, Xi; Zhang, Xiao; Wu, Zhan; Wang, Hongwei; Wang, Guohua; Li, Wei

    2017-11-01

    Social acquaintance networks influenced by social culture and social policy have a great impact on public opinion evolution in daily life. Based on the differences between socio-culture and social policy, three different social acquaintance networks (kinship-priority acquaintance network, independence-priority acquaintance network, and hybrid acquaintance network) incorporating heredity proportion ph and variation proportion pv are proposed in this paper. Numerical experiments are conducted to investigate network topology and different phenomena during opinion evolution, using the Deffuant model. We found that in kinship-priority acquaintance networks, similar to the Chinese traditional acquaintance networks, opinions always achieve fragmentation, resulting in the formation of multiple large clusters and many small clusters due to the fact that individuals believe more in their relatives and live in a relatively closed environment. In independence-priority acquaintance networks, similar to Western acquaintance networks, the results are similar to those in the kinship-priority acquaintance network. In hybrid acquaintance networks, similar to the Chinese modern acquaintance networks, only a few clusters are formed indicating that in modern China, opinions are more likely to reach consensus on a large scale. These results are similar to the opinion evolution phenomena in modern society, proving the rationality and applicability of network models combined with social culture and policy. We also found a threshold curve pv+2 ph=2.05 in the results for the final opinion clusters and evolution time. Above the threshold curve, opinions could easily reach consensus. Based on the above experimental results, a culture-policy-driven mechanism for the opinion dynamic is worth promoting in this paper, that is, opinion dynamics can be driven by different social cultures and policies through the influence of heredity and variation in interpersonal relationship networks. This

  12. Manufacturing network evolution

    DEFF Research Database (Denmark)

    Yang, Cheng; Farooq, Sami; Johansen, John

    2011-01-01

    Purpose – This paper examines the effect of changes at the manufacturing plant level on other plants in the manufacturing network and also investigates the role of manufacturing plants on the evolution of a manufacturing network. Design/methodology/approach –The research questions are developed...... different manufacturing plants in the network and their impact on network transformation. Findings – The paper highlights the dominant role of manufacturing plants in the continuously changing shape of a manufacturing network. The paper demonstrates that a product or process change at one manufacturing...... by identifying the gaps in the reviewed literature. The paper is based on three case studies undertaken in Danish manufacturing companies to explore in detail their manufacturing plants and networks. The cases provide a sound basis for developing the research questions and explaining the interaction between...

  13. Neutral evolution of proteins: The superfunnel in sequence space and its relation to mutational robustness

    Science.gov (United States)

    Noirel, Josselin; Simonson, Thomas

    2008-11-01

    Following Kimura's neutral theory of molecular evolution [M. Kimura, The Neutral Theory of Molecular Evolution (Cambridge University Press, Cambridge, 1983) (reprinted in 1986)], it has become common to assume that the vast majority of viable mutations of a gene confer little or no functional advantage. Yet, in silico models of protein evolution have shown that mutational robustness of sequences could be selected for, even in the context of neutral evolution. The evolution of a biological population can be seen as a diffusion on the network of viable sequences. This network is called a "neutral network." Depending on the mutation rate μ and the population size N, the biological population can evolve purely randomly (μN ≪1) or it can evolve in such a way as to select for sequences of higher mutational robustness (μN ≫1). The stringency of the selection depends not only on the product μN but also on the exact topology of the neutral network, the special arrangement of which was named "superfunnel." Even though the relation between mutation rate, population size, and selection was thoroughly investigated, a study of the salient topological features of the superfunnel that could affect the strength of the selection was wanting. This question is addressed in this study. We use two different models of proteins: on lattice and off lattice. We compare neutral networks computed using these models to random networks. From this, we identify two important factors of the topology that determine the stringency of the selection for mutationally robust sequences. First, the presence of highly connected nodes ("hubs") in the network increases the selection for mutationally robust sequences. Second, the stringency of the selection increases when the correlation between a sequence's mutational robustness and its neighbors' increases. The latter finding relates a global characteristic of the neutral network to a local one, which is attainable through experiments or molecular

  14. Opinion evolution in different social acquaintance networks.

    Science.gov (United States)

    Chen, Xi; Zhang, Xiao; Wu, Zhan; Wang, Hongwei; Wang, Guohua; Li, Wei

    2017-11-01

    Social acquaintance networks influenced by social culture and social policy have a great impact on public opinion evolution in daily life. Based on the differences between socio-culture and social policy, three different social acquaintance networks (kinship-priority acquaintance network, independence-priority acquaintance network, and hybrid acquaintance network) incorporating heredity proportion p h and variation proportion p v are proposed in this paper. Numerical experiments are conducted to investigate network topology and different phenomena during opinion evolution, using the Deffuant model. We found that in kinship-priority acquaintance networks, similar to the Chinese traditional acquaintance networks, opinions always achieve fragmentation, resulting in the formation of multiple large clusters and many small clusters due to the fact that individuals believe more in their relatives and live in a relatively closed environment. In independence-priority acquaintance networks, similar to Western acquaintance networks, the results are similar to those in the kinship-priority acquaintance network. In hybrid acquaintance networks, similar to the Chinese modern acquaintance networks, only a few clusters are formed indicating that in modern China, opinions are more likely to reach consensus on a large scale. These results are similar to the opinion evolution phenomena in modern society, proving the rationality and applicability of network models combined with social culture and policy. We also found a threshold curve p v +2p h =2.05 in the results for the final opinion clusters and evolution time. Above the threshold curve, opinions could easily reach consensus. Based on the above experimental results, a culture-policy-driven mechanism for the opinion dynamic is worth promoting in this paper, that is, opinion dynamics can be driven by different social cultures and policies through the influence of heredity and variation in interpersonal relationship networks. This

  15. Complex quantum network geometries: Evolution and phase transitions

    Science.gov (United States)

    Bianconi, Ginestra; Rahmede, Christoph; Wu, Zhihao

    2015-08-01

    Networks are topological and geometric structures used to describe systems as different as the Internet, the brain, or the quantum structure of space-time. Here we define complex quantum network geometries, describing the underlying structure of growing simplicial 2-complexes, i.e., simplicial complexes formed by triangles. These networks are geometric networks with energies of the links that grow according to a nonequilibrium dynamics. The evolution in time of the geometric networks is a classical evolution describing a given path of a path integral defining the evolution of quantum network states. The quantum network states are characterized by quantum occupation numbers that can be mapped, respectively, to the nodes, links, and triangles incident to each link of the network. We call the geometric networks describing the evolution of quantum network states the quantum geometric networks. The quantum geometric networks have many properties common to complex networks, including small-world property, high clustering coefficient, high modularity, and scale-free degree distribution. Moreover, they can be distinguished between the Fermi-Dirac network and the Bose-Einstein network obeying, respectively, the Fermi-Dirac and Bose-Einstein statistics. We show that these networks can undergo structural phase transitions where the geometrical properties of the networks change drastically. Finally, we comment on the relation between quantum complex network geometries, spin networks, and triangulations.

  16. Structural Evolution in Photoactive Yellow Protein Studied by Femtosecond Stimulated Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Yoshizawa M.

    2013-03-01

    Full Text Available Ultrafast structural evolution in photoactive yellow protein (PYP is studied by femtosecond stimulated Raman spectroscopy. A comparison between wild-type PYP and E46Q mutant reveals that the hydrogen-bonding network surrounding the chromophore of PYP is immediately rearranged in the electronic excited state.

  17. Evolution of metabolic network organization

    Directory of Open Access Journals (Sweden)

    Bonchev Danail

    2010-05-01

    Full Text Available Abstract Background Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints. Results We used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya, from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints. Conclusions Combining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules

  18. Plant Evolution: A Manufacturing Network Perspective

    DEFF Research Database (Denmark)

    Yang, Cheng; Johansen, John; Boer, Harry

    2009-01-01

    Viewing them as portfolios of products and processes, we aim to address how plants evolve in the context of a manufacturing network and how the evolution of one plant impacts other plants in the same manufacturing network. Based on discussions of ten plants from three Danish companies, we identify...... two different trajectories. Together, these trajectories determine the evolution of a manufacturing network. Factors appearing to affect the two trajectories include competencies built up, transferred or acquired locally, market potential, performance considerations, local, situational factors...

  19. Dynamic Evolution Model Based on Social Network Services

    Science.gov (United States)

    Xiong, Xi; Gou, Zhi-Jian; Zhang, Shi-Bin; Zhao, Wen

    2013-11-01

    Based on the analysis of evolutionary characteristics of public opinion in social networking services (SNS), in the paper we propose a dynamic evolution model, in which opinions are coupled with topology. This model shows the clustering phenomenon of opinions in dynamic network evolution. The simulation results show that the model can fit the data from a social network site. The dynamic evolution of networks accelerates the opinion, separation and aggregation. The scale and the number of clusters are influenced by confidence limit and rewiring probability. Dynamic changes of the topology reduce the number of isolated nodes, while the increased confidence limit allows nodes to communicate more sufficiently. The two effects make the distribution of opinion more neutral. The dynamic evolution of networks generates central clusters with high connectivity and high betweenness, which make it difficult to control public opinions in SNS.

  20. The role of exon shuffling in shaping protein-protein interaction networks

    Directory of Open Access Journals (Sweden)

    França Gustavo S

    2010-12-01

    Full Text Available Abstract Background Physical protein-protein interaction (PPI is a critical phenomenon for the function of most proteins in living organisms and a significant fraction of PPIs are the result of domain-domain interactions. Exon shuffling, intron-mediated recombination of exons from existing genes, is known to have been a major mechanism of domain shuffling in metazoans. Thus, we hypothesized that exon shuffling could have a significant influence in shaping the topology of PPI networks. Results We tested our hypothesis by compiling exon shuffling and PPI data from six eukaryotic species: Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Cryptococcus neoformans and Arabidopsis thaliana. For all four metazoan species, genes enriched in exon shuffling events presented on average higher vertex degree (number of interacting partners in PPI networks. Furthermore, we verified that a set of protein domains that are simultaneously promiscuous (known to interact to multiple types of other domains, self-interacting (able to interact with another copy of themselves and abundant in the genomes presents a stronger signal for exon shuffling. Conclusions Exon shuffling appears to have been a recurrent mechanism for the emergence of new PPIs along metazoan evolution. In metazoan genomes, exon shuffling also promoted the expansion of some protein domains. We speculate that their promiscuous and self-interacting properties may have been decisive for that expansion.

  1. Evolution of a large online social network

    International Nuclear Information System (INIS)

    Hu Haibo; Wang Xiaofan

    2009-01-01

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

  2. Divergent Evolution of the Transcriptional Network Controlled by Snf1-Interacting Protein Sip4 in Budding Yeasts.

    Directory of Open Access Journals (Sweden)

    Constance Mehlgarten

    Full Text Available Cellular responses to starvation are of ancient origin since nutrient limitation has always been a common challenge to the stability of living systems. Hence, signaling molecules involved in sensing or transducing information about limiting metabolites are highly conserved, whereas transcription factors and the genes they regulate have diverged. In eukaryotes the AMP-activated protein kinase (AMPK functions as a central regulator of cellular energy homeostasis. The yeast AMPK ortholog SNF1 controls the transcriptional network that counteracts carbon starvation conditions by regulating a set of transcription factors. Among those Cat8 and Sip4 have overlapping DNA-binding specificity for so-called carbon source responsive elements and induce target genes upon SNF1 activation. To analyze the evolution of the Cat8-Sip4 controlled transcriptional network we have compared the response to carbon limitation of Saccharomyces cerevisiae to that of Kluyveromyces lactis. In high glucose, S. cerevisiae displays tumor cell-like aerobic fermentation and repression of respiration (Crabtree-positive while K. lactis has a respiratory-fermentative life-style, respiration being regulated by oxygen availability (Crabtree-negative, which is typical for many yeasts and for differentiated higher cells. We demonstrate divergent evolution of the Cat8-Sip4 network and present evidence that a role of Sip4 in controlling anabolic metabolism has been lost in the Saccharomyces lineage. We find that in K. lactis, but not in S. cerevisiae, the Sip4 protein plays an essential role in C2 carbon assimilation including induction of the glyoxylate cycle and the carnitine shuttle genes. Induction of KlSIP4 gene expression by KlCat8 is essential under these growth conditions and a primary function of KlCat8. Both KlCat8 and KlSip4 are involved in the regulation of lactose metabolism in K. lactis. In chromatin-immunoprecipitation experiments we demonstrate binding of both, KlSip4 and

  3. Our interests in protein-protein interactions

    Indian Academy of Sciences (India)

    protein interactions. Evolution of P-P partnerships. Evolution of P-P structures. Evolutionary dynamics of P-P interactions. Dynamics of P-P interaction network. Host-pathogen interactions. CryoEM mapping of gigantic protein assemblies.

  4. Detection of protein complex from protein-protein interaction network using Markov clustering

    International Nuclear Information System (INIS)

    Ochieng, P J; Kusuma, W A; Haryanto, T

    2017-01-01

    Detection of complexes, or groups of functionally related proteins, is an important challenge while analysing biological networks. However, existing algorithms to identify protein complexes are insufficient when applied to dense networks of experimentally derived interaction data. Therefore, we introduced a graph clustering method based on Markov clustering algorithm to identify protein complex within highly interconnected protein-protein interaction networks. Protein-protein interaction network was first constructed to develop geometrical network, the network was then partitioned using Markov clustering to detect protein complexes. The interest of the proposed method was illustrated by its application to Human Proteins associated to type II diabetes mellitus. Flow simulation of MCL algorithm was initially performed and topological properties of the resultant network were analysed for detection of the protein complex. The results indicated the proposed method successfully detect an overall of 34 complexes with 11 complexes consisting of overlapping modules and 20 non-overlapping modules. The major complex consisted of 102 proteins and 521 interactions with cluster modularity and density of 0.745 and 0.101 respectively. The comparison analysis revealed MCL out perform AP, MCODE and SCPS algorithms with high clustering coefficient (0.751) network density and modularity index (0.630). This demonstrated MCL was the most reliable and efficient graph clustering algorithm for detection of protein complexes from PPI networks. (paper)

  5. SCM: A method to improve network service layout efficiency with network evolution

    Science.gov (United States)

    Zhao, Qi; Zhang, Chuanhao

    2017-01-01

    Network services are an important component of the Internet, which are used to expand network functions for third-party developers. Network function virtualization (NFV) can improve the speed and flexibility of network service deployment. However, with the evolution of the network, network service layout may become inefficient. Regarding this problem, this paper proposes a service chain migration (SCM) method with the framework of “software defined network + network function virtualization” (SDN+NFV), which migrates service chains to adapt to network evolution and improves the efficiency of the network service layout. SCM is modeled as an integer linear programming problem and resolved via particle swarm optimization. An SCM prototype system is designed based on an SDN controller. Experiments demonstrate that SCM could reduce the network traffic cost and energy consumption efficiently. PMID:29267299

  6. SCM: A method to improve network service layout efficiency with network evolution.

    Science.gov (United States)

    Zhao, Qi; Zhang, Chuanhao; Zhao, Zheng

    2017-01-01

    Network services are an important component of the Internet, which are used to expand network functions for third-party developers. Network function virtualization (NFV) can improve the speed and flexibility of network service deployment. However, with the evolution of the network, network service layout may become inefficient. Regarding this problem, this paper proposes a service chain migration (SCM) method with the framework of "software defined network + network function virtualization" (SDN+NFV), which migrates service chains to adapt to network evolution and improves the efficiency of the network service layout. SCM is modeled as an integer linear programming problem and resolved via particle swarm optimization. An SCM prototype system is designed based on an SDN controller. Experiments demonstrate that SCM could reduce the network traffic cost and energy consumption efficiently.

  7. The Evolution of Wikipedia’s Norm Network

    Directory of Open Access Journals (Sweden)

    Bradi Heaberlin

    2016-04-01

    Full Text Available Social norms have traditionally been difficult to quantify. In any particular society, their sheer number and complex interdependencies often limit a system-level analysis. One exception is that of the network of norms that sustain the online Wikipedia community. We study the fifteen-year evolution of this network using the interconnected set of pages that establish, describe, and interpret the community’s norms. Despite Wikipedia’s reputation for ad hoc governance, we find that its normative evolution is highly conservative. The earliest users create norms that both dominate the network and persist over time. These core norms govern both content and interpersonal interactions using abstract principles such as neutrality, verifiability, and assume good faith. As the network grows, norm neighborhoods decouple topologically from each other, while increasing in semantic coherence. Taken together, these results suggest that the evolution of Wikipedia’s norm network is akin to bureaucratic systems that predate the information age.

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

    Science.gov (United States)

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

    2013-01-01

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

  9. Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks

    Directory of Open Access Journals (Sweden)

    Boucher Charles AB

    2010-07-01

    Full Text Available Abstract Background The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics. Results Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems. Conclusions HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another.

  10. Evolution of hybrid defect networks

    International Nuclear Information System (INIS)

    Martins, C. J. A. P.

    2009-01-01

    We apply a recently developed analytic model for the evolution of monopole networks to the case of monopoles attached to one string, usually known as hybrid networks. We discuss scaling solutions for both local and global hybrid networks, and also find an interesting application for the case of vortons. Our quantitative results agree with previous estimates in indicating that the hybrid networks will usually annihilate soon after the string-forming phase transition. However, we also show that in some specific circumstances these networks can survive considerably more than a Hubble time.

  11. ELAV proteins along evolution: back to the nucleus?

    Science.gov (United States)

    Colombrita, Claudia; Silani, Vincenzo; Ratti, Antonia

    2013-09-01

    The complex interplay of post-transcriptional regulatory mechanisms mediated by RNA-binding proteins (RBP) at different steps of RNA metabolism is pivotal for the development of the nervous system and the maintenance of adult brain activities. In this review, we will focus on the highly conserved ELAV gene family encoding for neuronal-specific RBPs which are necessary for proper neuronal differentiation and important for synaptic plasticity process. In the evolution from Drosophila to man, ELAV proteins seem to have changed their biological functions in relation to their different subcellular localization. While in Drosophila, they are localized in the nuclear compartment of neuronal cells and regulate splicing and polyadenylation, in mammals, the neuronal ELAV proteins are mainly present in the cytoplasm where they participate in regulating mRNA target stability, translation and transport into neurites. However, recent data indicate that the mammalian ELAV RBPs also have nuclear activities, similarly to their fly counterpart, being them able to continuously shuttle between the cytoplasm and the nucleus. Here, we will review and comment on all the biological functions associated with neuronal ELAV proteins along evolution and will show that the post-transcriptional regulatory network mediated by these RBPs in the brain is highly complex and only at an initial stage of being fully understood. This article is part of a Special Issue entitled 'RNA and splicing regulation in neurodegeneration'. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Modeling Temporal Evolution and Multiscale Structure in Networks

    DEFF Research Database (Denmark)

    Herlau, Tue; Mørup, Morten; Schmidt, Mikkel Nørgaard

    2013-01-01

    Many real-world networks exhibit both temporal evolution and multiscale structure. We propose a model for temporally correlated multifurcating hierarchies in complex networks which jointly capture both effects. We use the Gibbs fragmentation tree as prior over multifurcating trees and a change......-point model to account for the temporal evolution of each vertex. We demonstrate that our model is able to infer time-varying multiscale structure in synthetic as well as three real world time-evolving complex networks. Our modeling of the temporal evolution of hierarchies brings new insights...

  13. Spectral affinity in protein networks.

    Science.gov (United States)

    Voevodski, Konstantin; Teng, Shang-Hua; Xia, Yu

    2009-11-29

    Protein-protein interaction (PPI) networks enable us to better understand the functional organization of the proteome. We can learn a lot about a particular protein by querying its neighborhood in a PPI network to find proteins with similar function. A spectral approach that considers random walks between nodes of interest is particularly useful in evaluating closeness in PPI networks. Spectral measures of closeness are more robust to noise in the data and are more precise than simpler methods based on edge density and shortest path length. We develop a novel affinity measure for pairs of proteins in PPI networks, which uses personalized PageRank, a random walk based method used in context-sensitive search on the Web. Our measure of closeness, which we call PageRank Affinity, is proportional to the number of times the smaller-degree protein is visited in a random walk that restarts at the larger-degree protein. PageRank considers paths of all lengths in a network, therefore PageRank Affinity is a precise measure that is robust to noise in the data. PageRank Affinity is also provably related to cluster co-membership, making it a meaningful measure. In our experiments on protein networks we find that our measure is better at predicting co-complex membership and finding functionally related proteins than other commonly used measures of closeness. Moreover, our experiments indicate that PageRank Affinity is very resilient to noise in the network. In addition, based on our method we build a tool that quickly finds nodes closest to a queried protein in any protein network, and easily scales to much larger biological networks. We define a meaningful way to assess the closeness of two proteins in a PPI network, and show that our closeness measure is more biologically significant than other commonly used methods. We also develop a tool, accessible at http://xialab.bu.edu/resources/pnns, that allows the user to quickly find nodes closest to a queried vertex in any protein

  14. Directed Evolution of Proteins through In Vitro Protein Synthesis in Liposomes

    Directory of Open Access Journals (Sweden)

    Takehiro Nishikawa

    2012-01-01

    Full Text Available Directed evolution of proteins is a technique used to modify protein functions through “Darwinian selection.” In vitro compartmentalization (IVC is an in vitro gene screening system for directed evolution of proteins. IVC establishes the link between genetic information (genotype and the protein translated from the information (phenotype, which is essential for all directed evolution methods, by encapsulating both in a nonliving microcompartment. Herein, we introduce a new liposome-based IVC system consisting of a liposome, the protein synthesis using recombinant elements (PURE system and a fluorescence-activated cell sorter (FACS used as a microcompartment, in vitro protein synthesis system, and high-throughput screen, respectively. Liposome-based IVC is characterized by in vitro protein synthesis from a single copy of a gene in a cell-sized unilamellar liposome and quantitative functional evaluation of the synthesized proteins. Examples of liposome-based IVC for screening proteins such as GFP and β-glucuronidase are described. We discuss the future directions for this method and its applications.

  15. Rapid evolution of coral proteins responsible for interaction with the environment.

    Science.gov (United States)

    Voolstra, Christian R; Sunagawa, Shinichi; Matz, Mikhail V; Bayer, Till; Aranda, Manuel; Buschiazzo, Emmanuel; Desalvo, Michael K; Lindquist, Erika; Szmant, Alina M; Coffroth, Mary Alice; Medina, Mónica

    2011-01-01

    Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change.

  16. Structure and Evolution of the Foreign Exchange Networks

    Science.gov (United States)

    Kwapień, J.; Gworek, S.; Drożdż, S.

    2009-01-01

    We investigate topology and temporal evolution of the foreign currency exchange market viewed from a weighted network perspective. Based on exchange rates for a set of 46 currencies (including precious metals), we construct different representations of the FX network depending on a choice of the base currency. Our results show that the network structure is not stable in time, but there are main clusters of currencies, which persist for a long period of time despite the fact that their size and content are variable. We find a long-term trend in the network's evolution which affects the USD and EUR nodes. In all the network representations, the USD node gradually loses its centrality, while, on contrary, the EUR node has become slightly more central than it used to be in its early years. Despite this directional trend, the overall evolution of the network is noisy.

  17. Evolution of the social network of scientific collaborations

    Science.gov (United States)

    Barabási, A. L.; Jeong, H.; Néda, Z.; Ravasz, E.; Schubert, A.; Vicsek, T.

    2002-08-01

    The co-authorship network of scientists represents a prototype of complex evolving networks. In addition, it offers one of the most extensive database to date on social networks. By mapping the electronic database containing all relevant journals in mathematics and neuro-science for an 8-year period (1991-98), we infer the dynamic and the structural mechanisms that govern the evolution and topology of this complex system. Three complementary approaches allow us to obtain a detailed characterization. First, empirical measurements allow us to uncover the topological measures that characterize the network at a given moment, as well as the time evolution of these quantities. The results indicate that the network is scale-free, and that the network evolution is governed by preferential attachment, affecting both internal and external links. However, in contrast with most model predictions the average degree increases in time, and the node separation decreases. Second, we propose a simple model that captures the network's time evolution. In some limits the model can be solved analytically, predicting a two-regime scaling in agreement with the measurements. Third, numerical simulations are used to uncover the behavior of quantities that could not be predicted analytically. The combined numerical and analytical results underline the important role internal links play in determining the observed scaling behavior and network topology. The results and methodologies developed in the context of the co-authorship network could be useful for a systematic study of other complex evolving networks as well, such as the world wide web, Internet, or other social networks.

  18. Spectral affinity in protein networks

    Directory of Open Access Journals (Sweden)

    Teng Shang-Hua

    2009-11-01

    Full Text Available Abstract Background Protein-protein interaction (PPI networks enable us to better understand the functional organization of the proteome. We can learn a lot about a particular protein by querying its neighborhood in a PPI network to find proteins with similar function. A spectral approach that considers random walks between nodes of interest is particularly useful in evaluating closeness in PPI networks. Spectral measures of closeness are more robust to noise in the data and are more precise than simpler methods based on edge density and shortest path length. Results We develop a novel affinity measure for pairs of proteins in PPI networks, which uses personalized PageRank, a random walk based method used in context-sensitive search on the Web. Our measure of closeness, which we call PageRank Affinity, is proportional to the number of times the smaller-degree protein is visited in a random walk that restarts at the larger-degree protein. PageRank considers paths of all lengths in a network, therefore PageRank Affinity is a precise measure that is robust to noise in the data. PageRank Affinity is also provably related to cluster co-membership, making it a meaningful measure. In our experiments on protein networks we find that our measure is better at predicting co-complex membership and finding functionally related proteins than other commonly used measures of closeness. Moreover, our experiments indicate that PageRank Affinity is very resilient to noise in the network. In addition, based on our method we build a tool that quickly finds nodes closest to a queried protein in any protein network, and easily scales to much larger biological networks. Conclusion We define a meaningful way to assess the closeness of two proteins in a PPI network, and show that our closeness measure is more biologically significant than other commonly used methods. We also develop a tool, accessible at http://xialab.bu.edu/resources/pnns, that allows the user to

  19. Cosmological evolution of p-brane networks

    International Nuclear Information System (INIS)

    Sousa, L.; Avelino, P. P.

    2011-01-01

    In this paper we derive, directly from the Nambu-Goto action, the relevant components of the acceleration of cosmological featureless p-branes, extending previous analysis based on the field theory equations in the thin-brane limit. The component of the acceleration parallel to the velocity is at the core of the velocity-dependent one-scale model for the evolution of p-brane networks. We use this model to show that, in a decelerating expanding universe in which the p-branes are relevant cosmologically, interactions cannot lead to frustration, except for fine-tuned nonrelativistic networks with a dimensionless curvature parameter k<<1. We discuss the implications of our findings for the cosmological evolution of p-brane networks.

  20. Structuring evolution: biochemical networks and metabolic diversification in birds.

    Science.gov (United States)

    Morrison, Erin S; Badyaev, Alexander V

    2016-08-25

    Recurrence and predictability of evolution are thought to reflect the correspondence between genomic and phenotypic dimensions of organisms, and the connectivity in deterministic networks within these dimensions. Direct examination of the correspondence between opportunities for diversification imbedded in such networks and realized diversity is illuminating, but is empirically challenging because both the deterministic networks and phenotypic diversity are modified in the course of evolution. Here we overcome this problem by directly comparing the structure of a "global" carotenoid network - comprising of all known enzymatic reactions among naturally occurring carotenoids - with the patterns of evolutionary diversification in carotenoid-producing metabolic networks utilized by birds. We found that phenotypic diversification in carotenoid networks across 250 species was closely associated with enzymatic connectivity of the underlying biochemical network - compounds with greater connectivity occurred the most frequently across species and were the hotspots of metabolic pathway diversification. In contrast, we found no evidence for diversification along the metabolic pathways, corroborating findings that the utilization of the global carotenoid network was not strongly influenced by history in avian evolution. The finding that the diversification in species-specific carotenoid networks is qualitatively predictable from the connectivity of the underlying enzymatic network points to significant structural determinism in phenotypic evolution.

  1. A last updating evolution model for online social networks

    Science.gov (United States)

    Bu, Zhan; Xia, Zhengyou; Wang, Jiandong; Zhang, Chengcui

    2013-05-01

    As information technology has advanced, people are turning to electronic media more frequently for communication, and social relationships are increasingly found on online channels. However, there is very limited knowledge about the actual evolution of the online social networks. In this paper, we propose and study a novel evolution network model with the new concept of “last updating time”, which exists in many real-life online social networks. The last updating evolution network model can maintain the robustness of scale-free networks and can improve the network reliance against intentional attacks. What is more, we also found that it has the “small-world effect”, which is the inherent property of most social networks. Simulation experiment based on this model show that the results and the real-life data are consistent, which means that our model is valid.

  2. Rapid evolution of coral proteins responsible for interaction with the environment.

    Directory of Open Access Journals (Sweden)

    Christian R Voolstra

    Full Text Available Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures, pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably.We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium.This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change.

  3. Rapid Evolution of Coral Proteins Responsible for Interaction with the Environment

    Energy Technology Data Exchange (ETDEWEB)

    Voolstra, Christian R.; Sunagawa, Shinichi; Matz, Mikhail V.; Bayer, Till; Aranda, Manuel; Buschiazzo, Emmanuel; DeSalvo, Michael K.; Lindquist, Erika; Szmant, Alina M.; Coffroth, Mary Alice; Medina, Monica

    2011-01-31

    Background: Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. Methodology/Principal Findings: We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7percent of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineagespecific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. Conclusion/Relevance: This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals? evolutionary response to global climate change.

  4. Unified Alignment of Protein-Protein Interaction Networks.

    Science.gov (United States)

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

    2017-04-19

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

  5. In-silico studies of neutral drift for functional protein interaction networks

    Science.gov (United States)

    Ali, Md Zulfikar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

    We have developed a minimal physically-motivated model of protein-protein interaction networks. Our system consists of two classes of enzymes, activators (e.g. kinases) and deactivators (e.g. phosphatases), and the enzyme-mediated activation/deactivation rates are determined by sequence-dependent binding strengths between enzymes and their targets. The network is evolved by introducing random point mutations in the binding sequences where we assume that each new mutation is either fixed or entirely lost. We apply this model to studies of neutral drift in networks that yield oscillatory dynamics, where we start, for example, with a relatively simple network and allow it to evolve by adding nodes and connections while requiring that dynamics be conserved. Our studies demonstrate both the importance of employing a sequence-based evolutionary scheme and the relative rapidity (in evolutionary time) for the redistribution of function over new nodes via neutral drift. Surprisingly, in addition to this redistribution time we discovered another much slower timescale for network evolution, reflecting hidden order in sequence space that we interpret in terms of sparsely connected domains.

  6. Intermediate filament protein evolution and protists.

    Science.gov (United States)

    Preisner, Harald; Habicht, Jörn; Garg, Sriram G; Gould, Sven B

    2018-03-23

    Metazoans evolved from a single protist lineage. While all eukaryotes share a conserved actin and tubulin-based cytoskeleton, it is commonly perceived that intermediate filaments (IFs), including lamin, vimentin or keratin among many others, are restricted to metazoans. Actin and tubulin proteins are conserved enough to be detectable across all eukaryotic genomes using standard phylogenetic methods, but IF proteins, in contrast, are notoriously difficult to identify by such means. Since the 1950s, dozens of cytoskeletal proteins in protists have been identified that seemingly do not belong to any of the IF families described for metazoans, yet, from a structural and functional perspective fit criteria that define metazoan IF proteins. Here, we briefly review IF protein discovery in metazoans and the implications this had for the definition of this protein family. We argue that the many cytoskeletal and filament-forming proteins of protists should be incorporated into a more comprehensive picture of IF evolution by aligning it with the recent identification of lamins across the phylogenetic diversity of eukaryotic supergroups. This then brings forth the question of how the diversity of IF proteins has unfolded. The evolution of IF proteins likely represents an example of convergent evolution, which, in combination with the speed with which these cytoskeletal proteins are evolving, generated their current diversity. IF proteins did not first emerge in metazoa, but in protists. Only the emergence of cytosolic IF proteins that appear to stem from a nuclear lamin is unique to animals and coincided with the emergence of true animal multicellularity. © 2018 Wiley Periodicals, Inc.

  7. A scored human protein-protein interaction network to catalyze genomic interpretation

    DEFF Research Database (Denmark)

    Li, Taibo; Wernersson, Rasmus; Hansen, Rasmus B

    2017-01-01

    Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (InWeb_InBioMap,......Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (In...

  8. Prediction of protein–protein interactions: unifying evolution and structure at protein interfaces

    International Nuclear Information System (INIS)

    Tuncbag, Nurcan; Gursoy, Attila; Keskin, Ozlem

    2011-01-01

    The vast majority of the chores in the living cell involve protein–protein interactions. Providing details of protein interactions at the residue level and incorporating them into protein interaction networks are crucial toward the elucidation of a dynamic picture of cells. Despite the rapid increase in the number of structurally known protein complexes, we are still far away from a complete network. Given experimental limitations, computational modeling of protein interactions is a prerequisite to proceed on the way to complete structural networks. In this work, we focus on the question 'how do proteins interact?' rather than 'which proteins interact?' and we review structure-based protein–protein interaction prediction approaches. As a sample approach for modeling protein interactions, PRISM is detailed which combines structural similarity and evolutionary conservation in protein interfaces to infer structures of complexes in the protein interaction network. This will ultimately help us to understand the role of protein interfaces in predicting bound conformations

  9. Human cancer protein-protein interaction network: a structural perspective.

    Directory of Open Access Journals (Sweden)

    Gozde Kar

    2009-12-01

    Full Text Available Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network. The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%. We illustrate the interface related affinity properties of two cancer-related hub

  10. Analyzing complex networks evolution through Information Theory quantifiers

    International Nuclear Information System (INIS)

    Carpi, Laura C.; Rosso, Osvaldo A.; Saco, Patricia M.; Ravetti, Martin Gomez

    2011-01-01

    A methodology to analyze dynamical changes in complex networks based on Information Theory quantifiers is proposed. The square root of the Jensen-Shannon divergence, a measure of dissimilarity between two probability distributions, and the MPR Statistical Complexity are used to quantify states in the network evolution process. Three cases are analyzed, the Watts-Strogatz model, a gene network during the progression of Alzheimer's disease and a climate network for the Tropical Pacific region to study the El Nino/Southern Oscillation (ENSO) dynamic. We find that the proposed quantifiers are able not only to capture changes in the dynamics of the processes but also to quantify and compare states in their evolution.

  11. The interface of protein structure, protein biophysics, and molecular evolution

    Science.gov (United States)

    Liberles, David A; Teichmann, Sarah A; Bahar, Ivet; Bastolla, Ugo; Bloom, Jesse; Bornberg-Bauer, Erich; Colwell, Lucy J; de Koning, A P Jason; Dokholyan, Nikolay V; Echave, Julian; Elofsson, Arne; Gerloff, Dietlind L; Goldstein, Richard A; Grahnen, Johan A; Holder, Mark T; Lakner, Clemens; Lartillot, Nicholas; Lovell, Simon C; Naylor, Gavin; Perica, Tina; Pollock, David D; Pupko, Tal; Regan, Lynne; Roger, Andrew; Rubinstein, Nimrod; Shakhnovich, Eugene; Sjölander, Kimmen; Sunyaev, Shamil; Teufel, Ashley I; Thorne, Jeffrey L; Thornton, Joseph W; Weinreich, Daniel M; Whelan, Simon

    2012-01-01

    Abstract The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction. PMID:22528593

  12. HKC: An Algorithm to Predict Protein Complexes in Protein-Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Xiaomin Wang

    2011-01-01

    Full Text Available With the availability of more and more genome-scale protein-protein interaction (PPI networks, research interests gradually shift to Systematic Analysis on these large data sets. A key topic is to predict protein complexes in PPI networks by identifying clusters that are densely connected within themselves but sparsely connected with the rest of the network. In this paper, we present a new topology-based algorithm, HKC, to detect protein complexes in genome-scale PPI networks. HKC mainly uses the concepts of highest k-core and cohesion to predict protein complexes by identifying overlapping clusters. The experiments on two data sets and two benchmarks show that our algorithm has relatively high F-measure and exhibits better performance compared with some other methods.

  13. Energy efficient evolution of mobile broadband networks

    Energy Technology Data Exchange (ETDEWEB)

    Micallef, G.

    2013-04-15

    Over the last decade, the mobile communications industry has broken through some remarkable barriers, pushing further and transforming the way people communicate and access information. As the volume of traffic carried by mobile networks maintains an insatiable growth, mobile network operators are required to ensure that networks can scale accordingly. In addition to upgrading existing networks, a number of operators have already started to rollout a further radio access technology layer, Long Term Evolution, or LTE. In addition to enhancing network capacity, operators are also required to adhere to public commitments for reducing their energy and carbon footprint. In 2008 Vodafone stated that by the year 2020, efforts for reducing emissions are expected to halve emissions registered in the year 2006/7. In addition to presenting a more environmentally conscious brand, this is also hoped to reduce costs, which, based on increasing energy prices and necessary network upgrades are likely to increase. Since base station sites make up for about 75% of the power consumption in mobile networks, studies are focused on this specific network element. A number of factors believed to play a role in the power consumption of mobile networks are separately investigated and later combined, providing a realistic indication of how the consumption is expected to evolve. This is also used as an indication to determine how likely it is for operators to achieve power consumption and emission targets. In order for mobile network operators to upgrade existing infrastructure different options are available. Irrespective of the selected option, capacity upgrades are bound to increase the power consumption of the network. Carried through case studies, a first analysis compares a number of network evolution strategies, determining which provides the necessary performance while limiting the increase in power consumption. Overall, it is noted that a hybrid solution involving the upgrade of

  14. Energy efficient evolution of mobile broadband networks

    Energy Technology Data Exchange (ETDEWEB)

    Micallef, G.

    2013-04-15

    Over the last decade, the mobile communications industry has broken through some remarkable barriers, pushing further and transforming the way people communicate and access information. As the volume of traffic carried by mobile networks maintains an insatiable growth, mobile network operators are required to ensure that networks can scale accordingly. In addition to upgrading existing networks, a number of operators have already started to rollout a further radio access technology layer, Long Term Evolution, or LTE. In addition to enhancing network capacity, operators are also required to adhere to public commitments for reducing their energy and carbon footprint. In 2008 Vodafone stated that by the year 2020, efforts for reducing emissions are expected to halve emissions registered in the year 2006/7. In addition to presenting a more environmentally conscious brand, this is also hoped to reduce costs, which, based on increasing energy prices and necessary network upgrades are likely to increase. Since base station sites make up for about 75% of the power consumption in mobile networks, studies are focused on this specific network element. A number of factors believed to play a role in the power consumption of mobile networks are separately investigated and later combined, providing a realistic indication of how the consumption is expected to evolve. This is also used as an indication to determine how likely it is for operators to achieve power consumption and emission targets. In order for mobile network operators to upgrade existing infrastructure different options are available. Irrespective of the selected option, capacity upgrades are bound to increase the power consumption of the network. Carried through case studies, a first analysis compares a number of network evolution strategies, determining which provides the necessary performance while limiting the increase in power consumption. Overall, it is noted that a hybrid solution involving the upgrade of

  15. Analyzing complex networks evolution through Information Theory quantifiers

    Energy Technology Data Exchange (ETDEWEB)

    Carpi, Laura C., E-mail: Laura.Carpi@studentmail.newcastle.edu.a [Civil, Surveying and Environmental Engineering, University of Newcastle, University Drive, Callaghan NSW 2308 (Australia); Departamento de Fisica, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte (31270-901), MG (Brazil); Rosso, Osvaldo A., E-mail: rosso@fisica.ufmg.b [Departamento de Fisica, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte (31270-901), MG (Brazil); Chaos and Biology Group, Instituto de Calculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon II, Ciudad Universitaria, 1428 Ciudad de Buenos Aires (Argentina); Saco, Patricia M., E-mail: Patricia.Saco@newcastle.edu.a [Civil, Surveying and Environmental Engineering, University of Newcastle, University Drive, Callaghan NSW 2308 (Australia); Departamento de Hidraulica, Facultad de Ciencias Exactas, Ingenieria y Agrimensura, Universidad Nacional de Rosario, Avenida Pellegrini 250, Rosario (Argentina); Ravetti, Martin Gomez, E-mail: martin.ravetti@dep.ufmg.b [Departamento de Engenharia de Producao, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte (31270-901), MG (Brazil)

    2011-01-24

    A methodology to analyze dynamical changes in complex networks based on Information Theory quantifiers is proposed. The square root of the Jensen-Shannon divergence, a measure of dissimilarity between two probability distributions, and the MPR Statistical Complexity are used to quantify states in the network evolution process. Three cases are analyzed, the Watts-Strogatz model, a gene network during the progression of Alzheimer's disease and a climate network for the Tropical Pacific region to study the El Nino/Southern Oscillation (ENSO) dynamic. We find that the proposed quantifiers are able not only to capture changes in the dynamics of the processes but also to quantify and compare states in their evolution.

  16. Network evolution model for supply chain with manufactures as the core

    Science.gov (United States)

    Jiang, Dali; Fang, Ling; Yang, Jian; Li, Wu; Zhao, Jing

    2018-01-01

    Building evolution model of supply chain networks could be helpful to understand its development law. However, specific characteristics and attributes of real supply chains are often neglected in existing evolution models. This work proposes a new evolution model of supply chain with manufactures as the core, based on external market demand and internal competition-cooperation. The evolution model assumes the external market environment is relatively stable, considers several factors, including specific topology of supply chain, external market demand, ecological growth and flow conservation. The simulation results suggest that the networks evolved by our model have similar structures as real supply chains. Meanwhile, the influences of external market demand and internal competition-cooperation to network evolution are analyzed. Additionally, 38 benchmark data sets are applied to validate the rationality of our evolution model, in which, nine manufacturing supply chains match the features of the networks constructed by our model. PMID:29370201

  17. Network evolution model for supply chain with manufactures as the core.

    Science.gov (United States)

    Fang, Haiyang; Jiang, Dali; Yang, Tinghong; Fang, Ling; Yang, Jian; Li, Wu; Zhao, Jing

    2018-01-01

    Building evolution model of supply chain networks could be helpful to understand its development law. However, specific characteristics and attributes of real supply chains are often neglected in existing evolution models. This work proposes a new evolution model of supply chain with manufactures as the core, based on external market demand and internal competition-cooperation. The evolution model assumes the external market environment is relatively stable, considers several factors, including specific topology of supply chain, external market demand, ecological growth and flow conservation. The simulation results suggest that the networks evolved by our model have similar structures as real supply chains. Meanwhile, the influences of external market demand and internal competition-cooperation to network evolution are analyzed. Additionally, 38 benchmark data sets are applied to validate the rationality of our evolution model, in which, nine manufacturing supply chains match the features of the networks constructed by our model.

  18. Network evolution model for supply chain with manufactures as the core.

    Directory of Open Access Journals (Sweden)

    Haiyang Fang

    Full Text Available Building evolution model of supply chain networks could be helpful to understand its development law. However, specific characteristics and attributes of real supply chains are often neglected in existing evolution models. This work proposes a new evolution model of supply chain with manufactures as the core, based on external market demand and internal competition-cooperation. The evolution model assumes the external market environment is relatively stable, considers several factors, including specific topology of supply chain, external market demand, ecological growth and flow conservation. The simulation results suggest that the networks evolved by our model have similar structures as real supply chains. Meanwhile, the influences of external market demand and internal competition-cooperation to network evolution are analyzed. Additionally, 38 benchmark data sets are applied to validate the rationality of our evolution model, in which, nine manufacturing supply chains match the features of the networks constructed by our model.

  19. A model for evolution of overlapping community networks

    Science.gov (United States)

    Karan, Rituraj; Biswal, Bibhu

    2017-05-01

    A model is proposed for the evolution of network topology in social networks with overlapping community structure. Starting from an initial community structure that is defined in terms of group affiliations, the model postulates that the subsequent growth and loss of connections is similar to the Hebbian learning and unlearning in the brain and is governed by two dominant factors: the strength and frequency of interaction between the members, and the degree of overlap between different communities. The temporal evolution from an initial community structure to the current network topology can be described based on these two parameters. It is possible to quantify the growth occurred so far and predict the final stationary state to which the network is likely to evolve. Applications in epidemiology or the spread of email virus in a computer network as well as finding specific target nodes to control it are envisaged. While facing the challenge of collecting and analyzing large-scale time-resolved data on social groups and communities one faces the most basic questions: how do communities evolve in time? This work aims to address this issue by developing a mathematical model for the evolution of community networks and studying it through computer simulation.

  20. Integration of Structural Dynamics and Molecular Evolution via Protein Interaction Networks: A New Era in Genomic Medicine

    Science.gov (United States)

    Kumar, Avishek; Butler, Brandon M.; Kumar, Sudhir; Ozkan, S. Banu

    2016-01-01

    Summary Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine. PMID:26684487

  1. Origin and evolution of chromosomal sperm proteins.

    Science.gov (United States)

    Eirín-López, José M; Ausió, Juan

    2009-10-01

    In the eukaryotic cell, DNA compaction is achieved through its interaction with histones, constituting a nucleoprotein complex called chromatin. During metazoan evolution, the different structural and functional constraints imposed on the somatic and germinal cell lines led to a unique process of specialization of the sperm nuclear basic proteins (SNBPs) associated with chromatin in male germ cells. SNBPs encompass a heterogeneous group of proteins which, since their discovery in the nineteenth century, have been studied extensively in different organisms. However, the origin and controversial mechanisms driving the evolution of this group of proteins has only recently started to be understood. Here, we analyze in detail the histone hypothesis for the vertical parallel evolution of SNBPs, involving a "vertical" transition from a histone to a protamine-like and finally protamine types (H --> PL --> P), the last one of which is present in the sperm of organisms at the uppermost tips of the phylogenetic tree. In particular, the common ancestry shared by the protamine-like (PL)- and protamine (P)-types with histone H1 is discussed within the context of the diverse structural and functional constraints acting upon these proteins during bilaterian evolution.

  2. Oligomeric protein structure networks: insights into protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Brinda KV

    2005-12-01

    Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

  3. Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine.

    Science.gov (United States)

    Kumar, Avishek; Butler, Brandon M; Kumar, Sudhir; Ozkan, S Banu

    2015-12-01

    Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Prediction of Protein-Protein Interactions Related to Protein Complexes Based on Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Peng Liu

    2015-01-01

    Full Text Available A method for predicting protein-protein interactions based on detected protein complexes is proposed to repair deficient interactions derived from high-throughput biological experiments. Protein complexes are pruned and decomposed into small parts based on the adaptive k-cores method to predict protein-protein interactions associated with the complexes. The proposed method is adaptive to protein complexes with different structure, number, and size of nodes in a protein-protein interaction network. Based on different complex sets detected by various algorithms, we can obtain different prediction sets of protein-protein interactions. The reliability of the predicted interaction sets is proved by using estimations with statistical tests and direct confirmation of the biological data. In comparison with the approaches which predict the interactions based on the cliques, the overlap of the predictions is small. Similarly, the overlaps among the predicted sets of interactions derived from various complex sets are also small. Thus, every predicted set of interactions may complement and improve the quality of the original network data. Meanwhile, the predictions from the proposed method replenish protein-protein interactions associated with protein complexes using only the network topology.

  5. Topology evolution in macromolecular networks

    NARCIS (Netherlands)

    Kryven, I.

    2014-01-01

    Governed by various intermolecular forces, molecular networks tend to evolve from simple to very complex formations that have random structure. This randomness in the connectivity of the basic units can still be captured employing distributional description of the state of the system; the evolution

  6. Research on social communication network evolution based on topology potential distribution

    Science.gov (United States)

    Zhao, Dongjie; Jiang, Jian; Li, Deyi; Zhang, Haisu; Chen, Guisheng

    2011-12-01

    Aiming at the problem of social communication network evolution, first, topology potential is introduced to measure the local influence among nodes in networks. Second, from the perspective of topology potential distribution the method of network evolution description based on topology potential distribution is presented, which takes the artificial intelligence with uncertainty as basic theory and local influence among nodes as essentiality. Then, a social communication network is constructed by enron email dataset, the method presented is used to analyze the characteristic of the social communication network evolution and some useful conclusions are got, implying that the method is effective, which shows that topology potential distribution can effectively describe the characteristic of sociology and detect the local changes in social communication network.

  7. Influence of degree correlations on network structure and stability in protein-protein interaction networks

    Directory of Open Access Journals (Sweden)

    Zimmer Ralf

    2007-08-01

    Full Text Available Abstract Background The existence of negative correlations between degrees of interacting proteins is being discussed since such negative degree correlations were found for the large-scale yeast protein-protein interaction (PPI network of Ito et al. More recent studies observed no such negative correlations for high-confidence interaction sets. In this article, we analyzed a range of experimentally derived interaction networks to understand the role and prevalence of degree correlations in PPI networks. We investigated how degree correlations influence the structure of networks and their tolerance against perturbations such as the targeted deletion of hubs. Results For each PPI network, we simulated uncorrelated, positively and negatively correlated reference networks. Here, a simple model was developed which can create different types of degree correlations in a network without changing the degree distribution. Differences in static properties associated with degree correlations were compared by analyzing the network characteristics of the original PPI and reference networks. Dynamics were compared by simulating the effect of a selective deletion of hubs in all networks. Conclusion Considerable differences between the network types were found for the number of components in the original networks. Negatively correlated networks are fragmented into significantly less components than observed for positively correlated networks. On the other hand, the selective deletion of hubs showed an increased structural tolerance to these deletions for the positively correlated networks. This results in a lower rate of interaction loss in these networks compared to the negatively correlated networks and a decreased disintegration rate. Interestingly, real PPI networks are most similar to the randomly correlated references with respect to all properties analyzed. Thus, although structural properties of networks can be modified considerably by degree

  8. Network analysis of metabolic enzyme evolution in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Kraulis Per

    2004-02-01

    Full Text Available Abstract Background The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc. Results Sequence comparison between all enzyme pairs was performed and the minimal path length (MPL between all enzyme pairs was determined. We find a strong over-representation of homologous enzymes at MPL 1. We show that the functionally similar and functionally undetermined enzyme pairs are responsible for most of the over-representation of homologous enzyme pairs at MPL 1. Conclusions The retrograde evolution model predicts that homologous enzymes pairs are at short metabolic distances from each other. In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model. However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs. Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

  9. An analysis pipeline for the inference of protein-protein interaction networks

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Ronald C.; Singhal, Mudita; Daly, Don S.; Gilmore, Jason M.; Cannon, William R.; Domico, Kelly O.; White, Amanda M.; Auberry, Deanna L.; Auberry, Kenneth J.; Hooker, Brian S.; Hurst, G. B.; McDermott, Jason E.; McDonald, W. H.; Pelletier, Dale A.; Schmoyer, Denise A.; Wiley, H. S.

    2009-12-01

    An analysis pipeline has been created for deployment of a novel algorithm, the Bayesian Estimator of Protein-Protein Association Probabilities (BEPro), for use in the reconstruction of protein-protein interaction networks. We have combined the Software Environment for BIological Network Inference (SEBINI), an interactive environment for the deployment and testing of network inference algorithms that use high-throughput data, and the Collective Analysis of Biological Interaction Networks (CABIN), software that allows integration and analysis of protein-protein interaction and gene-to-gene regulatory evidence obtained from multiple sources, to allow interactions computed by BEPro to be stored, visualized, and further analyzed. Incorporating BEPro into SEBINI and automatically feeding the resulting inferred network into CABIN, we have created a structured workflow for protein-protein network inference and supplemental analysis from sets of mass spectrometry bait-prey experiment data. SEBINI demo site: https://www.emsl.pnl.gov /SEBINI/ Contact: ronald.taylor@pnl.gov. BEPro is available at http://www.pnl.gov/statistics/BEPro3/index.htm. Contact: ds.daly@pnl.gov. CABIN is available at http://www.sysbio.org/dataresources/cabin.stm. Contact: mudita.singhal@pnl.gov.

  10. A Bayesian approach to the evolution of metabolic networks on a phylogeny.

    Directory of Open Access Journals (Sweden)

    Aziz Mithani

    2010-08-01

    Full Text Available The availability of genomes of many closely related bacteria with diverse metabolic capabilities offers the possibility of tracing metabolic evolution on a phylogeny relating the genomes to understand the evolutionary processes and constraints that affect the evolution of metabolic networks. Using simple (independent loss/gain of reactions or complex (incorporating dependencies among reactions stochastic models of metabolic evolution, it is possible to study how metabolic networks evolve over time. Here, we describe a model that takes the reaction neighborhood into account when modeling metabolic evolution. The model also allows estimation of the strength of the neighborhood effect during the course of evolution. We present Gibbs samplers for sampling networks at the internal node of a phylogeny and for estimating the parameters of evolution over a phylogeny without exploring the whole search space by iteratively sampling from the conditional distributions of the internal networks and parameters. The samplers are used to estimate the parameters of evolution of metabolic networks of bacteria in the genus Pseudomonas and to infer the metabolic networks of the ancestral pseudomonads. The results suggest that pathway maps that are conserved across the Pseudomonas phylogeny have a stronger neighborhood structure than those which have a variable distribution of reactions across the phylogeny, and that some Pseudomonas lineages are going through genome reduction resulting in the loss of a number of reactions from their metabolic networks.

  11. DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network.

    Science.gov (United States)

    Mistry, Divya; Wise, Roger P; Dickerson, Julie A

    2017-01-01

    Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be

  12. Social network analysis community detection and evolution

    CERN Document Server

    Missaoui, Rokia

    2015-01-01

    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

  13. Pareto evolution of gene networks: an algorithm to optimize multiple fitness objectives

    International Nuclear Information System (INIS)

    Warmflash, Aryeh; Siggia, Eric D; Francois, Paul

    2012-01-01

    The computational evolution of gene networks functions like a forward genetic screen to generate, without preconceptions, all networks that can be assembled from a defined list of parts to implement a given function. Frequently networks are subject to multiple design criteria that cannot all be optimized simultaneously. To explore how these tradeoffs interact with evolution, we implement Pareto optimization in the context of gene network evolution. In response to a temporal pulse of a signal, we evolve networks whose output turns on slowly after the pulse begins, and shuts down rapidly when the pulse terminates. The best performing networks under our conditions do not fall into categories such as feed forward and negative feedback that also encode the input–output relation we used for selection. Pareto evolution can more efficiently search the space of networks than optimization based on a single ad hoc combination of the design criteria. (paper)

  14. Pareto evolution of gene networks: an algorithm to optimize multiple fitness objectives.

    Science.gov (United States)

    Warmflash, Aryeh; Francois, Paul; Siggia, Eric D

    2012-10-01

    The computational evolution of gene networks functions like a forward genetic screen to generate, without preconceptions, all networks that can be assembled from a defined list of parts to implement a given function. Frequently networks are subject to multiple design criteria that cannot all be optimized simultaneously. To explore how these tradeoffs interact with evolution, we implement Pareto optimization in the context of gene network evolution. In response to a temporal pulse of a signal, we evolve networks whose output turns on slowly after the pulse begins, and shuts down rapidly when the pulse terminates. The best performing networks under our conditions do not fall into categories such as feed forward and negative feedback that also encode the input-output relation we used for selection. Pareto evolution can more efficiently search the space of networks than optimization based on a single ad hoc combination of the design criteria.

  15. Structural Approaches to Sequence Evolution Molecules, Networks, Populations

    CERN Document Server

    Bastolla, Ugo; Roman, H. Eduardo; Vendruscolo, Michele

    2007-01-01

    Structural requirements constrain the evolution of biological entities at all levels, from macromolecules to their networks, right up to populations of biological organisms. Classical models of molecular evolution, however, are focused at the level of the symbols - the biological sequence - rather than that of their resulting structure. Now recent advances in understanding the thermodynamics of macromolecules, the topological properties of gene networks, the organization and mutation capabilities of genomes, and the structure of populations make it possible to incorporate these key elements into a broader and deeply interdisciplinary view of molecular evolution. This book gives an account of such a new approach, through clear tutorial contributions by leading scientists specializing in the different fields involved.

  16. Recurrent rewiring and emergence of RNA regulatory networks.

    Science.gov (United States)

    Wilinski, Daniel; Buter, Natascha; Klocko, Andrew D; Lapointe, Christopher P; Selker, Eric U; Gasch, Audrey P; Wickens, Marvin

    2017-04-04

    Alterations in regulatory networks contribute to evolutionary change. Transcriptional networks are reconfigured by changes in the binding specificity of transcription factors and their cognate sites. The evolution of RNA-protein regulatory networks is far less understood. The PUF (Pumilio and FBF) family of RNA regulatory proteins controls the translation, stability, and movements of hundreds of mRNAs in a single species. We probe the evolution of PUF-RNA networks by direct identification of the mRNAs bound to PUF proteins in budding and filamentous fungi and by computational analyses of orthologous RNAs from 62 fungal species. Our findings reveal that PUF proteins gain and lose mRNAs with related and emergent biological functions during evolution. We demonstrate at least two independent rewiring events for PUF3 orthologs, independent but convergent evolution of PUF4/5 binding specificity and the rewiring of the PUF4/5 regulons in different fungal lineages. These findings demonstrate plasticity in RNA regulatory networks and suggest ways in which their rewiring occurs.

  17. Protein function prediction using neighbor relativity in protein-protein interaction network.

    Science.gov (United States)

    Moosavi, Sobhan; Rahgozar, Masoud; Rahimi, Amir

    2013-04-01

    There is a large gap between the number of discovered proteins and the number of functionally annotated ones. Due to the high cost of determining protein function by wet-lab research, function prediction has become a major task for computational biology and bioinformatics. Some researches utilize the proteins interaction information to predict function for un-annotated proteins. In this paper, we propose a novel approach called "Neighbor Relativity Coefficient" (NRC) based on interaction network topology which estimates the functional similarity between two proteins. NRC is calculated for each pair of proteins based on their graph-based features including distance, common neighbors and the number of paths between them. In order to ascribe function to an un-annotated protein, NRC estimates a weight for each neighbor to transfer its annotation to the unknown protein. Finally, the unknown protein will be annotated by the top score transferred functions. We also investigate the effect of using different coefficients for various types of functions. The proposed method has been evaluated on Saccharomyces cerevisiae and Homo sapiens interaction networks. The performance analysis demonstrates that NRC yields better results in comparison with previous protein function prediction approaches that utilize interaction network. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Protein Networks in Alzheimer's Disease

    DEFF Research Database (Denmark)

    Carlsen, Eva Meier; Rasmussen, Rune

    2017-01-01

    Overlap of RNA and protein networks reveals glia cells as key players for the development of symptomatic Alzheimer’s disease in humans......Overlap of RNA and protein networks reveals glia cells as key players for the development of symptomatic Alzheimer’s disease in humans...

  19. A Multilevel Network Study of the Effects of Delinquent Behavior on Friendship Evolution

    NARCIS (Netherlands)

    Snijders, T.A.B.; Baerveldt, Chris

    2003-01-01

    A multilevel approach is proposed to the study of the evolution of multiple networks. In this approach, the basic evolution process is assumed to be the same, while parameter values may differ between different networks. For the network evolution process, stochastic actor-oriented models are used,

  20. Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

    Science.gov (United States)

    Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

    2015-12-01

    Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

  1. The evolution of cooperation on geographical networks

    Science.gov (United States)

    Li, Yixiao; Wang, Yi; Sheng, Jichuan

    2017-11-01

    We study evolutionary public goods game on geographical networks, i.e., complex networks which are located on a geographical plane. The geographical feature effects in two ways: In one way, the geographically-induced network structure influences the overall evolutionary dynamics, and, in the other way, the geographical length of an edge influences the cost when the two players at the two ends interact. For the latter effect, we design a new cost function of cooperators, which simply assumes that the longer the distance between two players, the higher cost the cooperator(s) of them have to pay. In this study, network substrates are generated by a previous spatial network model with a cost-benefit parameter controlling the network topology. Our simulations show that the greatest promotion of cooperation is achieved in the intermediate regime of the parameter, in which empirical estimates of various railway networks fall. Further, we investigate how the distribution of edges' geographical costs influences the evolutionary dynamics and consider three patterns of the distribution: an approximately-equal distribution, a diverse distribution, and a polarized distribution. For normal geographical networks which are generated using intermediate values of the cost-benefit parameter, a diverse distribution hinders the evolution of cooperation, whereas a polarized distribution lowers the threshold value of the amplification factor for cooperation in public goods game. These results are helpful for understanding the evolution of cooperation on real-world geographical networks.

  2. Selfish cellular networks and the evolution of complex organisms.

    Science.gov (United States)

    Kourilsky, Philippe

    2012-03-01

    Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells. A wealth of literature shows that these individual cellular networks are complex, robust and evolvable. To some extent, they are able to monitor their own performance, and display sufficient autonomy to be termed "selfish". Their robustness is linked to quality control mechanisms which are embedded in and act upon the individual networks, thereby providing a basis for selection during gametogenesis. These selective processes are equally likely to affect cellular functions that are not gamete-specific, and the evolution of the most complex organisms, including man, is therefore likely to occur via two pathways: essential housekeeping functions would be regulated and evolve during gametogenesis within the parents before being transmitted to their progeny, while classical selection would operate on other traits of the organisms that shape their fitness with respect to the environment. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  3. Evolution of students’ friendship networks: Examining the influence of group size

    Directory of Open Access Journals (Sweden)

    Valentina Sokolovska

    2017-01-01

    Full Text Available  The main aim of this study was to examine the effect of the network size on formation and evolution of students’ friendship relations. Data was collected from two groups of sociology freshmen: a group from the University of Belgrade, which represents a larger group, and a group from the University of Novi Sad, which represents a smaller group. The data was collected in three periods of one academic year. We analyzed the structural features of students’ networks and constructed a stochastic model of network evolution in order to explore how friendships form and change during one year. The results showed that structural features of the larger and the smaller group differ in each stage of friendship formation. At the beginning of group forming, small world structure was noticeable in the larger group, although full small world structure was not confirmed in both groups. Furthermore, transitivity of triads had effect on the evolution of the larger network, while balance or structural equivalence had effect on the evolution of the smaller network. Results of the structural analysis are in line with findings of the network evolution model and together they provide an insight into how friendship evolves in groups of different sizes.

  4. Duplicate retention in signalling proteins and constraints from network dynamics.

    Science.gov (United States)

    Soyer, O S; Creevey, C J

    2010-11-01

    Duplications are a major driving force behind evolution. Most duplicates are believed to fix through genetic drift, but it is not clear whether this process affects all duplications equally or whether there are certain gene families that are expected to show neutral expansions under certain circumstances. Here, we analyse the neutrality of duplications in different functional classes of signalling proteins based on their effects on response dynamics. We find that duplications involving intermediary proteins in a signalling network are neutral more often than those involving receptors. Although the fraction of neutral duplications in all functional classes increase with decreasing population size and selective pressure on dynamics, this effect is most pronounced for receptors, indicating a possible expansion of receptors in species with small population size. In line with such an expectation, we found a statistically significant increase in the number of receptors as a fraction of genome size in eukaryotes compared with prokaryotes. Although not confirmative, these results indicate that neutral processes can be a significant factor in shaping signalling networks and affect proteins from different functional classes differently. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

  5. Molecular clock in neutral protein evolution

    Directory of Open Access Journals (Sweden)

    Wilke Claus O

    2004-08-01

    Full Text Available Abstract Background A frequent observation in molecular evolution is that amino-acid substitution rates show an index of dispersion (that is, ratio of variance to mean substantially larger than one. This observation has been termed the overdispersed molecular clock. On the basis of in silico protein-evolution experiments, Bastolla and coworkers recently proposed an explanation for this observation: Proteins drift in neutral space, and can temporarily get trapped in regions of substantially reduced neutrality. In these regions, substitution rates are suppressed, which results in an overall substitution process that is not Poissonian. However, the simulation method of Bastolla et al. is representative only for cases in which the product of mutation rate μ and population size Ne is small. How the substitution process behaves when μNe is large is not known. Results Here, I study the behavior of the molecular clock in in silico protein evolution as a function of mutation rate and population size. I find that the index of dispersion decays with increasing μNe, and approaches 1 for large μNe . This observation can be explained with the selective pressure for mutational robustness, which is effective when μNe is large. This pressure keeps the population out of low-neutrality traps, and thus steadies the ticking of the molecular clock. Conclusions The molecular clock in neutral protein evolution can fall into two distinct regimes, a strongly overdispersed one for small μNe, and a mostly Poissonian one for large μNe. The former is relevant for the majority of organisms in the plant and animal kingdom, and the latter may be relevant for RNA viruses.

  6. Evolution of individual versus social learning on social networks.

    Science.gov (United States)

    Tamura, Kohei; Kobayashi, Yutaka; Ihara, Yasuo

    2015-03-06

    A number of studies have investigated the roles played by individual and social learning in cultural phenomena and the relative advantages of the two learning strategies in variable environments. Because social learning involves the acquisition of behaviours from others, its utility depends on the availability of 'cultural models' exhibiting adaptive behaviours. This indicates that social networks play an essential role in the evolution of learning. However, possible effects of social structure on the evolution of learning have not been fully explored. Here, we develop a mathematical model to explore the evolutionary dynamics of learning strategies on social networks. We first derive the condition under which social learners (SLs) are selectively favoured over individual learners in a broad range of social network. We then obtain an analytical approximation of the long-term average frequency of SLs in homogeneous networks, from which we specify the condition, in terms of three relatedness measures, for social structure to facilitate the long-term evolution of social learning. Finally, we evaluate our approximation by Monte Carlo simulations in complete graphs, regular random graphs and scale-free networks. We formally show that whether social structure favours the evolution of social learning is determined by the relative magnitudes of two effects of social structure: localization in competition, by which competition between learning strategies is evaded, and localization in cultural transmission, which slows down the spread of adaptive traits. In addition, our estimates of the relatedness measures suggest that social structure disfavours the evolution of social learning when selection is weak. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  7. Network Compression as a Quality Measure for Protein Interaction Networks

    Science.gov (United States)

    Royer, Loic; Reimann, Matthias; Stewart, A. Francis; Schroeder, Michael

    2012-01-01

    With the advent of large-scale protein interaction studies, there is much debate about data quality. Can different noise levels in the measurements be assessed by analyzing network structure? Because proteomic regulation is inherently co-operative, modular and redundant, it is inherently compressible when represented as a network. Here we propose that network compression can be used to compare false positive and false negative noise levels in protein interaction networks. We validate this hypothesis by first confirming the detrimental effect of false positives and false negatives. Second, we show that gold standard networks are more compressible. Third, we show that compressibility correlates with co-expression, co-localization, and shared function. Fourth, we also observe correlation with better protein tagging methods, physiological expression in contrast to over-expression of tagged proteins, and smart pooling approaches for yeast two-hybrid screens. Overall, this new measure is a proxy for both sensitivity and specificity and gives complementary information to standard measures such as average degree and clustering coefficients. PMID:22719828

  8. Identification of Top-ranked Proteins within a Directional Protein Interaction Network using the PageRank Algorithm: Applications in Humans and Plants.

    Science.gov (United States)

    Li, Xiu-Qing; Xing, Tim; Du, Donglei

    2016-01-01

    Somatic mutation of signal transduction genes or key nodes of the cellular protein network can cause severe diseases in humans but can sometimes genetically improve plants, likely because growth is determinate in animals but indeterminate in plants. This article reviews protein networks; human protein ranking; the mitogen-activated protein kinase (MAPK) and insulin (phospho- inositide 3kinase [PI3K]/phosphatase and tensin homolog [PTEN]/protein kinase B [AKT]) signaling pathways; human diseases caused by somatic mutations to the PI3K/PTEN/ AKT pathway; use of the MAPK pathway in plant molecular breeding; and protein domain evolution. Casitas B-lineage lymphoma (CBL), PTEN, MAPK1 and PIK3CA are among PIK3CA the top-ranked proteins in directional rankings. Eight proteins (ACVR1, CDC42, RAC1, RAF1, RHOA, TGFBR1, TRAF2, and TRAF6) are ranked in the top 50 key players in both signal emission and signal reception and in interaction with many other proteins. Top-ranked proteins likely have major impacts on the network function. Such proteins are targets for drug discovery, because their mutations are implicated in various cancers and overgrowth syndromes. Appropriately managing food intake may help reduce the growth of tumors or malformation of tissues. The role of the protein kinase C/ fatty acid synthase pathway in fat deposition in PTEN/PI3K patients should be investigated. Both the MAPK and insulin signaling pathways exist in plants, and MAPK pathway engineering can improve plant tolerance to biotic and abiotic stresses such as salinity.

  9. Evolution of Wireless Sensor Networks for Industrial Control

    Directory of Open Access Journals (Sweden)

    Arthur Low

    2013-05-01

    Full Text Available Technologies evolve in a process of gradual scientific change, but the commercial application of technologies is discontinuous. Managers interested in technology evolution can integrate these contrasting ideas using a powerful theoretical framework, based on the concept of punctuated equilibrium from evolutionary biology. The framework, which enables the differentiation of the technical evolution of a technology from its market application, is used in this article to compare the two standards for wireless sensor networks (WSN for industrial instrumentation and control: WirelessHART and ISA100.11a. The two WSN standards are the product of two different market contexts, which have selected different minimum viable technologies for evolution in their respective niches. Network security issues present some important selection criteria. Both WSN standards implement security countermeasures against localized wireless network attacks based on the application of the AES encryption standard, but some specific security threats – some local, others remotely launched – are only well-defended by the adoption of public-key cryptographic (PKC protocols, which only ISA100.11a supports. This article concludes that the mainstream market potential of the Internet has influenced the evolution of ISA100.11a and will continue to demand that each WSN standard evolve in ways that are difficult to predict.

  10. Evolution properties of the community members for dynamic networks

    Science.gov (United States)

    Yang, Kai; Guo, Qiang; Li, Sheng-Nan; Han, Jing-Ti; Liu, Jian-Guo

    2017-03-01

    The collective behaviors of community members for dynamic social networks are significant for understanding evolution features of communities. In this Letter, we empirically investigate the evolution properties of the new community members for dynamic networks. Firstly, we separate data sets into different slices, and analyze the statistical properties of new members as well as communities they joined in for these data sets. Then we introduce a parameter φ to describe community evolution between different slices and investigate the dynamic community properties of the new community members. The empirical analyses for the Facebook, APS, Enron and Wiki data sets indicate that both the number of new members and joint communities increase, the ratio declines rapidly and then becomes stable over time, and most of the new members will join in the small size communities that is s ≤ 10. Furthermore, the proportion of new members in existed communities decreases firstly and then becomes stable and relatively small for these data sets. Our work may be helpful for deeply understanding the evolution properties of community members for social networks.

  11. The Origin and Early Evolution of Membrane Proteins

    Science.gov (United States)

    Pohorille, Andrew; Schweighofter, Karl; Wilson, Michael A.

    2006-01-01

    The origin and early evolution of membrane proteins, and in particular ion channels, are considered from the point of view that the transmembrane segments of membrane proteins are structurally quite simple and do not require specific sequences to fold. We argue that the transport of solute species, especially ions, required an early evolution of efficient transport mechanisms, and that the emergence of simple ion channels was protobiologically plausible. We also argue that, despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. These properties can be subtly modulated by local modifications to the sequence rather than global changes in molecular architecture. In order to address the evolution and development of ion channels, we focus on identifying those protein domains that are commonly associated with ion channel proteins and are conserved throughout the three main domains of life (Eukarya, Prokarya, and Archaea). We discuss the potassium-sodium-calcium superfamily of voltage-gated ion channels, mechanosensitive channels, porins, and ABC-transporters and argue that these families of membrane channels have sufficiently universal architectures that they can readily adapt to the diverse functional demands arising during evolution.

  12. Evolution of semilocal string networks. II. Velocity estimators

    Science.gov (United States)

    Lopez-Eiguren, A.; Urrestilla, J.; Achúcarro, A.; Avgoustidis, A.; Martins, C. J. A. P.

    2017-07-01

    We continue a comprehensive numerical study of semilocal string networks and their cosmological evolution. These can be thought of as hybrid networks comprised of (nontopological) string segments, whose core structure is similar to that of Abelian Higgs vortices, and whose ends have long-range interactions and behavior similar to that of global monopoles. Our study provides further evidence of a linear scaling regime, already reported in previous studies, for the typical length scale and velocity of the network. We introduce a new algorithm to identify the position of the segment cores. This allows us to determine the length and velocity of each individual segment and follow their evolution in time. We study the statistical distribution of segment lengths and velocities for radiation- and matter-dominated evolution in the regime where the strings are stable. Our segment detection algorithm gives higher length values than previous studies based on indirect detection methods. The statistical distribution shows no evidence of (anti)correlation between the speed and the length of the segments.

  13. Finding local communities in protein networks.

    Science.gov (United States)

    Voevodski, Konstantin; Teng, Shang-Hua; Xia, Yu

    2009-09-18

    Protein-protein interactions (PPIs) play fundamental roles in nearly all biological processes, and provide major insights into the inner workings of cells. A vast amount of PPI data for various organisms is available from BioGRID and other sources. The identification of communities in PPI networks is of great interest because they often reveal previously unknown functional ties between proteins. A large number of global clustering algorithms have been applied to protein networks, where the entire network is partitioned into clusters. Here we take a different approach by looking for local communities in PPI networks. We develop a tool, named Local Protein Community Finder, which quickly finds a community close to a queried protein in any network available from BioGRID or specified by the user. Our tool uses two new local clustering algorithms Nibble and PageRank-Nibble, which look for a good cluster among the most popular destinations of a short random walk from the queried vertex. The quality of a cluster is determined by proportion of outgoing edges, known as conductance, which is a relative measure particularly useful in undersampled networks. We show that the two local clustering algorithms find communities that not only form excellent clusters, but are also likely to be biologically relevant functional components. We compare the performance of Nibble and PageRank-Nibble to other popular and effective graph partitioning algorithms, and show that they find better clusters in the graph. Moreover, Nibble and PageRank-Nibble find communities that are more functionally coherent. The Local Protein Community Finder, accessible at http://xialab.bu.edu/resources/lpcf, allows the user to quickly find a high-quality community close to a queried protein in any network available from BioGRID or specified by the user. We show that the communities found by our tool form good clusters and are functionally coherent, making our application useful for biologists who wish to

  14. Finding local communities in protein networks

    Directory of Open Access Journals (Sweden)

    Teng Shang-Hua

    2009-09-01

    Full Text Available Abstract Background Protein-protein interactions (PPIs play fundamental roles in nearly all biological processes, and provide major insights into the inner workings of cells. A vast amount of PPI data for various organisms is available from BioGRID and other sources. The identification of communities in PPI networks is of great interest because they often reveal previously unknown functional ties between proteins. A large number of global clustering algorithms have been applied to protein networks, where the entire network is partitioned into clusters. Here we take a different approach by looking for local communities in PPI networks. Results We develop a tool, named Local Protein Community Finder, which quickly finds a community close to a queried protein in any network available from BioGRID or specified by the user. Our tool uses two new local clustering algorithms Nibble and PageRank-Nibble, which look for a good cluster among the most popular destinations of a short random walk from the queried vertex. The quality of a cluster is determined by proportion of outgoing edges, known as conductance, which is a relative measure particularly useful in undersampled networks. We show that the two local clustering algorithms find communities that not only form excellent clusters, but are also likely to be biologically relevant functional components. We compare the performance of Nibble and PageRank-Nibble to other popular and effective graph partitioning algorithms, and show that they find better clusters in the graph. Moreover, Nibble and PageRank-Nibble find communities that are more functionally coherent. Conclusion The Local Protein Community Finder, accessible at http://xialab.bu.edu/resources/lpcf, allows the user to quickly find a high-quality community close to a queried protein in any network available from BioGRID or specified by the user. We show that the communities found by our tool form good clusters and are functionally coherent

  15. NAPS: Network Analysis of Protein Structures

    Science.gov (United States)

    Chakrabarty, Broto; Parekh, Nita

    2016-01-01

    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:http://bioinf.iiit.ac.in/NAPS/. PMID:27151201

  16. Evolution of regulatory networks towards adaptability and stability in a changing environment

    Science.gov (United States)

    Lee, Deok-Sun

    2014-11-01

    Diverse biological networks exhibit universal features distinguished from those of random networks, calling much attention to their origins and implications. Here we propose a minimal evolution model of Boolean regulatory networks, which evolve by selectively rewiring links towards enhancing adaptability to a changing environment and stability against dynamical perturbations. We find that sparse and heterogeneous connectivity patterns emerge, which show qualitative agreement with real transcriptional regulatory networks and metabolic networks. The characteristic scaling behavior of stability reflects the balance between robustness and flexibility. The scaling of fluctuation in the perturbation spread shows a dynamic crossover, which is analyzed by investigating separately the stochasticity of internal dynamics and the network structure differences depending on the evolution pathways. Our study delineates how the ambivalent pressure of evolution shapes biological networks, which can be helpful for studying general complex systems interacting with environments.

  17. Regulation, Competition and Network Evolution in Aviation

    Science.gov (United States)

    Gillen, David; Morrison, William

    2003-01-01

    Our focus is the evolution of business strategies and network structure decisions in the commercial passenger aviation industry. The paper reviews the growth of hub-and-spoke networks as the dominant business model following deregulation in the latter part of the 20 century, followed by the emergence of value-based airlines as a global phenomenon at the end of the century. The paper highlights the link between airline business strategies and network structures, and examines the resulting competition between divergent network structure business models. In this context we discuss issues of market structure stability and the role played by competition policy.

  18. Effective comparative analysis of protein-protein interaction networks by measuring the steady-state network flow using a Markov model.

    Science.gov (United States)

    Jeong, Hyundoo; Qian, Xiaoning; Yoon, Byung-Jun

    2016-10-06

    Comparative analysis of protein-protein interaction (PPI) networks provides an effective means of detecting conserved functional network modules across different species. Such modules typically consist of orthologous proteins with conserved interactions, which can be exploited to computationally predict the modules through network comparison. In this work, we propose a novel probabilistic framework for comparing PPI networks and effectively predicting the correspondence between proteins, represented as network nodes, that belong to conserved functional modules across the given PPI networks. The basic idea is to estimate the steady-state network flow between nodes that belong to different PPI networks based on a Markov random walk model. The random walker is designed to make random moves to adjacent nodes within a PPI network as well as cross-network moves between potential orthologous nodes with high sequence similarity. Based on this Markov random walk model, we estimate the steady-state network flow - or the long-term relative frequency of the transitions that the random walker makes - between nodes in different PPI networks, which can be used as a probabilistic score measuring their potential correspondence. Subsequently, the estimated scores can be used for detecting orthologous proteins in conserved functional modules through network alignment. Through evaluations based on multiple real PPI networks, we demonstrate that the proposed scheme leads to improved alignment results that are biologically more meaningful at reduced computational cost, outperforming the current state-of-the-art algorithms. The source code and datasets can be downloaded from http://www.ece.tamu.edu/~bjyoon/CUFID .

  19. Classification of Beta-lactamases and penicillin binding proteins using ligand-centric network models.

    Directory of Open Access Journals (Sweden)

    Hakime Öztürk

    Full Text Available β-lactamase mediated antibiotic resistance is an important health issue and the discovery of new β-lactam type antibiotics or β-lactamase inhibitors is an area of intense research. Today, there are about a thousand β-lactamases due to the evolutionary pressure exerted by these ligands. While β-lactamases hydrolyse the β-lactam ring of antibiotics, rendering them ineffective, Penicillin-Binding Proteins (PBPs, which share high structural similarity with β-lactamases, also confer antibiotic resistance to their host organism by acquiring mutations that allow them to continue their participation in cell wall biosynthesis. In this paper, we propose a novel approach to include ligand sharing information for classifying and clustering β-lactamases and PBPs in an effort to elucidate the ligand induced evolution of these β-lactam binding proteins. We first present a detailed summary of the β-lactamase and PBP families in the Protein Data Bank, as well as the compounds they bind to. Then, we build two different types of networks in which the proteins are represented as nodes, and two proteins are connected by an edge with a weight that depends on the number of shared identical or similar ligands. These models are analyzed under three different edge weight settings, namely unweighted, weighted, and normalized weighted. A detailed comparison of these six networks showed that the use of ligand sharing information to cluster proteins resulted in modules comprising proteins with not only sequence similarity but also functional similarity. Consideration of ligand similarity highlighted some interactions that were not detected in the identical ligand network. Analysing the β-lactamases and PBPs using ligand-centric network models enabled the identification of novel relationships, suggesting that these models can be used to examine other protein families to obtain information on their ligand induced evolutionary paths.

  20. 3DProIN: Protein-Protein Interaction Networks and Structure Visualization.

    Science.gov (United States)

    Li, Hui; Liu, Chunmei

    2014-06-14

    3DProIN is a computational tool to visualize protein-protein interaction networks in both two dimensional (2D) and three dimensional (3D) view. It models protein-protein interactions in a graph and explores the biologically relevant features of the tertiary structures of each protein in the network. Properties such as color, shape and name of each node (protein) of the network can be edited in either 2D or 3D views. 3DProIN is implemented using 3D Java and C programming languages. The internet crawl technique is also used to parse dynamically grasped protein interactions from protein data bank (PDB). It is a java applet component that is embedded in the web page and it can be used on different platforms including Linux, Mac and Window using web browsers such as Firefox, Internet Explorer, Chrome and Safari. It also was converted into a mac app and submitted to the App store as a free app. Mac users can also download the app from our website. 3DProIN is available for academic research at http://bicompute.appspot.com.

  1. Prediction and characterization of protein-protein interaction networks in swine

    Directory of Open Access Journals (Sweden)

    Wang Fen

    2012-01-01

    Full Text Available Abstract Background Studying the large-scale protein-protein interaction (PPI network is important in understanding biological processes. The current research presents the first PPI map of swine, which aims to give new insights into understanding their biological processes. Results We used three methods, Interolog-based prediction of porcine PPI network, domain-motif interactions from structural topology-based prediction of porcine PPI network and motif-motif interactions from structural topology-based prediction of porcine PPI network, to predict porcine protein interactions among 25,767 porcine proteins. We predicted 20,213, 331,484, and 218,705 porcine PPIs respectively, merged the three results into 567,441 PPIs, constructed four PPI networks, and analyzed the topological properties of the porcine PPI networks. Our predictions were validated with Pfam domain annotations and GO annotations. Averages of 70, 10,495, and 863 interactions were related to the Pfam domain-interacting pairs in iPfam database. For comparison, randomized networks were generated, and averages of only 4.24, 66.79, and 44.26 interactions were associated with Pfam domain-interacting pairs in iPfam database. In GO annotations, we found 52.68%, 75.54%, 27.20% of the predicted PPIs sharing GO terms respectively. However, the number of PPI pairs sharing GO terms in the 10,000 randomized networks reached 52.68%, 75.54%, 27.20% is 0. Finally, we determined the accuracy and precision of the methods. The methods yielded accuracies of 0.92, 0.53, and 0.50 at precisions of about 0.93, 0.74, and 0.75, respectively. Conclusion The results reveal that the predicted PPI networks are considerably reliable. The present research is an important pioneering work on protein function research. The porcine PPI data set, the confidence score of each interaction and a list of related data are available at (http://pppid.biositemap.com/.

  2. Directed evolution of an extremely stable fluorescent protein.

    Science.gov (United States)

    Kiss, Csaba; Temirov, Jamshid; Chasteen, Leslie; Waldo, Geoffrey S; Bradbury, Andrew R M

    2009-05-01

    In this paper we describe the evolution of eCGP123, an extremely stable green fluorescent protein based on a previously described fluorescent protein created by consensus engineering (CGP: consensus green protein). eCGP123 could not be denatured by a standard thermal melt, preserved almost full fluorescence after overnight incubation at 80 degrees C and possessed a free energy of denaturation of 12.4 kcal/mol. It was created from CGP by a recursive process involving the sequential introduction of three destabilizing heterologous inserts, evolution to overcome the destabilization and finally 'removal' of the destabilizing insert by gene synthesis. We believe that this approach may be generally applicable to the stabilization of other proteins.

  3. Earth Regimes Network Evolution Study (ERNESt): Introducing the Space Mobile Network

    Science.gov (United States)

    Menrad, Bob

    2016-01-01

    Speaker and Presenter at the Lincoln Laboratory Communications Workshop on April 5, 2016 at the Massachusetts Institute of Technology Lincoln Laboratory in Lexington, MA. A visual presentation titled Earth Regimes Network Evolution Study (ERNESt).

  4. Interworking evolution of mobile satellite and terrestrial networks

    Science.gov (United States)

    Matyas, R.; Kelleher, P.; Moller, P.; Jones, T.

    1993-01-01

    There is considerable interest among mobile satellite service providers in interworking with terrestrial networks to provide a universal global network. With such interworking, subscribers may be provided a common set of services such as those planned for the Public Switched Telephone Network (PSTN), the Integrated Services Digital Network (ISDN), and future Intelligent Networks (IN's). This paper first reviews issues in satellite interworking. Next the status and interworking plans of terrestrial mobile communications service providers are examined with early examples of mobile satellite interworking including a discussion of the anticipated evolution towards full interworking between mobile satellite and both fixed and mobile terrestrial networks.

  5. Construction of ontology augmented networks for protein complex prediction.

    Science.gov (United States)

    Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian

    2013-01-01

    Protein complexes are of great importance in understanding the principles of cellular organization and function. The increase in available protein-protein interaction data, gene ontology and other resources make it possible to develop computational methods for protein complex prediction. Most existing methods focus mainly on the topological structure of protein-protein interaction networks, and largely ignore the gene ontology annotation information. In this article, we constructed ontology augmented networks with protein-protein interaction data and gene ontology, which effectively unified the topological structure of protein-protein interaction networks and the similarity of gene ontology annotations into unified distance measures. After constructing ontology augmented networks, a novel method (clustering based on ontology augmented networks) was proposed to predict protein complexes, which was capable of taking into account the topological structure of the protein-protein interaction network, as well as the similarity of gene ontology annotations. Our method was applied to two different yeast protein-protein interaction datasets and predicted many well-known complexes. The experimental results showed that (i) ontology augmented networks and the unified distance measure can effectively combine the structure closeness and gene ontology annotation similarity; (ii) our method is valuable in predicting protein complexes and has higher F1 and accuracy compared to other competing methods.

  6. Discovering disease-associated genes in weighted protein-protein interaction networks

    Science.gov (United States)

    Cui, Ying; Cai, Meng; Stanley, H. Eugene

    2018-04-01

    Although there have been many network-based attempts to discover disease-associated genes, most of them have not taken edge weight - which quantifies their relative strength - into consideration. We use connection weights in a protein-protein interaction (PPI) network to locate disease-related genes. We analyze the topological properties of both weighted and unweighted PPI networks and design an improved random forest classifier to distinguish disease genes from non-disease genes. We use a cross-validation test to confirm that weighted networks are better able to discover disease-associated genes than unweighted networks, which indicates that including link weight in the analysis of network properties provides a better model of complex genotype-phenotype associations.

  7. Simulating evolution of protein complexes through gene duplication and co-option.

    Science.gov (United States)

    Haarsma, Loren; Nelesen, Serita; VanAndel, Ethan; Lamine, James; VandeHaar, Peter

    2016-06-21

    We present a model of the evolution of protein complexes with novel functions through gene duplication, mutation, and co-option. Under a wide variety of input parameters, digital organisms evolve complexes of 2-5 bound proteins which have novel functions but whose component proteins are not independently functional. Evolution of complexes with novel functions happens more quickly as gene duplication rates increase, point mutation rates increase, protein complex functional probability increases, protein complex functional strength increases, and protein family size decreases. Evolution of complexity is inhibited when the metabolic costs of making proteins exceeds the fitness gain of having functional proteins, or when point mutation rates get so large the functional proteins undergo deleterious mutations faster than new functional complexes can evolve. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Evolution of Cooperation in Adaptive Social Networks

    Science.gov (United States)

    Segbroeck, Sven Van; Santos, Francisco C.; Traulsen, Arne; Lenaerts, Tom; Pacheco, Jorge M.

    Humans are organized in societies, a phenomenon that would never have been possible without the evolution of cooperative behavior. Several mechanisms that foster this evolution have been unraveled over the years, with population structure as a prominent promoter of cooperation. Modern networks of exchange and cooperation are, however, becoming increasingly volatile, and less and less based on long-term stable structure. Here, we address how this change of paradigm aspects the evolution of cooperation. We discuss analytical and numerical models in which individuals can break social ties and create new ones. Interactions are modeled as two-player dilemmas of cooperation. Once a link between two individuals has formed, the productivity of this link is evaluated. Links can be broken off at different rates. This individual capacity of forming new links or severing inconvenient ones can effectively change the nature of the game. We address random formation of new links and local linking rules as well as different individual capacities to maintain social interactions. We conclude by discussing how adaptive social networks can become an important step towards more realistic models of cultural dynamics.

  9. Energy Efficient Evolution of Mobile Networks

    DEFF Research Database (Denmark)

    Micallef, Gilbert; Mogensen, Preben

    2011-01-01

    options for how to evolve their networks, allowing them to carry the expected increase in traffic. The best solution is generally selected based on two main criteria, performance and cost. However, pushed by a variety of environmental and energy challenges, MNOs are now also showing interest...... in understanding the impact that different options can have on the energy consumption of their networks. This paper investigates the possible energy gains of evolving a mobile network through a joint pico deployment and macro upgrade solution over a period of 8 years. Besides the network energy consumption, energy...... efficiency in Mbps/kWh is also analyzed. Furthermore, a cost analysis is carried out, to give a more complete picture of the different options being considered. Focusing on the last year of the evolution analysis, results show that deploying more pico sites reduces the energy consumption of the network...

  10. Clustering and visualizing similarity networks of membrane proteins.

    Science.gov (United States)

    Hu, Geng-Ming; Mai, Te-Lun; Chen, Chi-Ming

    2015-08-01

    We proposed a fast and unsupervised clustering method, minimum span clustering (MSC), for analyzing the sequence-structure-function relationship of biological networks, and demonstrated its validity in clustering the sequence/structure similarity networks (SSN) of 682 membrane protein (MP) chains. The MSC clustering of MPs based on their sequence information was found to be consistent with their tertiary structures and functions. For the largest seven clusters predicted by MSC, the consistency in chain function within the same cluster is found to be 100%. From analyzing the edge distribution of SSN for MPs, we found a characteristic threshold distance for the boundary between clusters, over which SSN of MPs could be properly clustered by an unsupervised sparsification of the network distance matrix. The clustering results of MPs from both MSC and the unsupervised sparsification methods are consistent with each other, and have high intracluster similarity and low intercluster similarity in sequence, structure, and function. Our study showed a strong sequence-structure-function relationship of MPs. We discussed evidence of convergent evolution of MPs and suggested applications in finding structural similarities and predicting biological functions of MP chains based on their sequence information. © 2015 Wiley Periodicals, Inc.

  11. Dynamic Evolution of Financial Network and its Relation to Economic Crises

    Science.gov (United States)

    Gao, Ya-Chun; Wei, Zong-Wen; Wang, Bing-Hong

    2013-02-01

    The static topology properties of financial networks have been widely investigated since the work done by Mantegna, yet their dynamic evolution with time is little considered. In this paper, we comprehensively study the dynamic evolution of financial network by a sliding window technique. The vertices and edges of financial network are represented by the stocks from S&P500 components and correlations between pairs of daily returns of price fluctuation, respectively. Furthermore, the duration of stock price fluctuation, spanning from January 4, 1985 to September 14, 2009, makes us to carefully observe the relation between the dynamic topological properties and big financial crashes. The empirical results suggest that the financial network has the robust small-world property when the time evolves, and the topological structure drastically changes when the big financial crashes occur. This correspondence between the dynamic evolution of financial network and big financial crashes may provide a novel view to understand the origin of economic crisis.

  12. Predicting Community Evolution in Social Networks

    Directory of Open Access Journals (Sweden)

    Stanisław Saganowski

    2015-05-01

    Full Text Available Nowadays, sustained development of different social media can be observed worldwide. One of the relevant research domains intensively explored recently is analysis of social communities existing in social media as well as prediction of their future evolution taking into account collected historical evolution chains. These evolution chains proposed in the paper contain group states in the previous time frames and its historical transitions that were identified using one out of two methods: Stable Group Changes Identification (SGCI and Group Evolution Discovery (GED. Based on the observed evolution chains of various length, structural network features are extracted, validated and selected as well as used to learn classification models. The experimental studies were performed on three real datasets with different profile: DBLP, Facebook and Polish blogosphere. The process of group prediction was analysed with respect to different classifiers as well as various descriptive feature sets extracted from evolution chains of different length. The results revealed that, in general, the longer evolution chains the better predictive abilities of the classification models. However, chains of length 3 to 7 enabled the GED-based method to almost reach its maximum possible prediction quality. For SGCI, this value was at the level of 3–5 last periods.

  13. Discriminating lysosomal membrane protein types using dynamic neural network.

    Science.gov (United States)

    Tripathi, Vijay; Gupta, Dwijendra Kumar

    2014-01-01

    This work presents a dynamic artificial neural network methodology, which classifies the proteins into their classes from their sequences alone: the lysosomal membrane protein classes and the various other membranes protein classes. In this paper, neural networks-based lysosomal-associated membrane protein type prediction system is proposed. Different protein sequence representations are fused to extract the features of a protein sequence, which includes seven feature sets; amino acid (AA) composition, sequence length, hydrophobic group, electronic group, sum of hydrophobicity, R-group, and dipeptide composition. To reduce the dimensionality of the large feature vector, we applied the principal component analysis. The probabilistic neural network, generalized regression neural network, and Elman regression neural network (RNN) are used as classifiers and compared with layer recurrent network (LRN), a dynamic network. The dynamic networks have memory, i.e. its output depends not only on the input but the previous outputs also. Thus, the accuracy of LRN classifier among all other artificial neural networks comes out to be the highest. The overall accuracy of jackknife cross-validation is 93.2% for the data-set. These predicted results suggest that the method can be effectively applied to discriminate lysosomal associated membrane proteins from other membrane proteins (Type-I, Outer membrane proteins, GPI-Anchored) and Globular proteins, and it also indicates that the protein sequence representation can better reflect the core feature of membrane proteins than the classical AA composition.

  14. Unconventional computing using evolution-in-nanomaterio: neural networks meet nanoparticle networks

    NARCIS (Netherlands)

    Greff, Klaus; van Damme, Rudolf M.J.; Koutnik, Jan; Broersma, Haitze J.; Mikhal, Julia Olegivna; Lawrence, Celestine Preetham; van der Wiel, Wilfred Gerard; Schmidhuber, Jürgen

    2016-01-01

    Recently published experimental work on evolution-in-materio applied to nanoscale materials shows promising results for future reconfigurable devices. These experiments were performed on disordered nano-particle networks that have no predefined design. The material has been treated as a blackbox,

  15. NatalieQ: A web server for protein-protein interaction network querying

    NARCIS (Netherlands)

    El-Kebir, M.; Brandt, B.W.; Heringa, J.; Klau, G.W.

    2014-01-01

    Background Molecular interactions need to be taken into account to adequately model the complex behavior of biological systems. These interactions are captured by various types of biological networks, such as metabolic, gene-regulatory, signal transduction and protein-protein interaction networks.

  16. Predicting the evolution of social networks with life cycle events

    NARCIS (Netherlands)

    Sharmeen, F.; Arentze, T.A.; Timmermans, H.J.P.

    2015-01-01

    This paper presents a model of social network evolution, to predict and simulate changes in social networks induced by lifecycle events. We argue that social networks change with lifecycle events, and we extend a model of friendship selection to incorporate these dynamics of personal social

  17. Analysis of protein-protein interaction networks by means of annotated graph mining algorithms

    NARCIS (Netherlands)

    Rahmani, Hossein

    2012-01-01

    This thesis discusses solutions to several open problems in Protein-Protein Interaction (PPI) networks with the aid of Knowledge Discovery. PPI networks are usually represented as undirected graphs, with nodes corresponding to proteins and edges representing interactions among protein pairs. A large

  18. Nation-Wide Mobile Network Energy Evolution Analysis

    DEFF Research Database (Denmark)

    Perez, Eva; Frank, Philipp; Micallef, Gilbert

    2013-01-01

    Mobile network operators are facing a challenging dilemma. While on the one hand they are committed to reducing their carbon emissions, and energy consumption, they are also required to continuously upgrade existing networks, ensuring that the relentless growth in data traffic can still be suppor......Mobile network operators are facing a challenging dilemma. While on the one hand they are committed to reducing their carbon emissions, and energy consumption, they are also required to continuously upgrade existing networks, ensuring that the relentless growth in data traffic can still...... be supported. In most cases, these upgrades increase the energy consumption of the network even further. This paper presents a nation-wide case study, based on a commercial network of a leading European operator, intended to provide a clear understanding of how the energy consumption of mobile networks...... is expected to evolve from 2012 until 2020. The study also considers an efficient network capacity evolution path, including base station equipment improvement forecasts....

  19. Analytic models for the evolution of semilocal string networks

    International Nuclear Information System (INIS)

    Nunes, A. S.; Martins, C. J. A. P.; Avgoustidis, A.; Urrestilla, J.

    2011-01-01

    We revisit previously developed analytic models for defect evolution and adapt them appropriately for the study of semilocal string networks. We thus confirm the expectation (based on numerical simulations) that linear scaling evolution is the attractor solution for a broad range of model parameters. We discuss in detail the evolution of individual semilocal segments, focusing on the phenomenology of segment growth, and also provide a preliminary comparison with existing numerical simulations.

  20. A study on the evolution of crack networks under thermal fatigue loading

    International Nuclear Information System (INIS)

    Kamaya, Masayuki; Taheri, Said

    2008-01-01

    The crack network is a typical cracking morphology caused by thermal fatigue loading. It was pointed out that the crack network appeared under relatively small temperature fluctuations and did not grow deeply. In this study, the mechanism of evolution of crack network and its influence on crack growth was examined by numerical calculation. First, the stress field near two interacting cracks was investigated. It was shown that there are stress-concentration and stress-shielding zones around interacting cracks, and that cracks can form a network under the bi-axial stress condition. Secondly, a Monte Carlo simulation was developed in order to simulate the initiation and growth of cracks under thermal fatigue loading and the evolution of the crack network. The local stress field formed by pre-existing cracks was evaluated by the body force method and its role in the initiation and growth of cracks was considered. The simulation could simulate the evolution of the crack network and change in number of cracks observed in the experiments. It was revealed that reduction in the stress intensity factor due to stress feature in the depth direction under high cycle thermal fatigue loading plays an important role in the evolution of the crack network and that mechanical interaction between cracks in the network affects initiation rather than growth of cracks. The crack network appears only when the crack growth in the depth direction is interrupted. It was concluded that the emergence of the crack network is preferable for the structural integrity of cracked components

  1. Co-evolution of social networks and continuous actor attributes

    NARCIS (Netherlands)

    Niezink, Nynke M.D.; Snijders, Tom A.B.

    2017-01-01

    Social networks and the attributes of the actors in these networks are not static; they may develop interdependently over time. The stochastic actor-oriented model allows for statistical inference on the mechanisms driving this co-evolution process. In earlier versions of this model, dynamic actor

  2. Protein enriched pasta: structure and digestibility of its protein network.

    Science.gov (United States)

    Laleg, Karima; Barron, Cécile; Santé-Lhoutellier, Véronique; Walrand, Stéphane; Micard, Valérie

    2016-02-01

    Wheat (W) pasta was enriched in 6% gluten (G), 35% faba (F) or 5% egg (E) to increase its protein content (13% to 17%). The impact of the enrichment on the multiscale structure of the pasta and on in vitro protein digestibility was studied. Increasing the protein content (W- vs. G-pasta) strengthened pasta structure at molecular and macroscopic scales but reduced its protein digestibility by 3% by forming a higher covalently linked protein network. Greater changes in the macroscopic and molecular structure of the pasta were obtained by varying the nature of protein used for enrichment. Proteins in G- and E-pasta were highly covalently linked (28-32%) resulting in a strong pasta structure. Conversely, F-protein (98% SDS-soluble) altered the pasta structure by diluting gluten and formed a weak protein network (18% covalent link). As a result, protein digestibility in F-pasta was significantly higher (46%) than in E- (44%) and G-pasta (39%). The effect of low (55 °C, LT) vs. very high temperature (90 °C, VHT) drying on the protein network structure and digestibility was shown to cause greater molecular changes than pasta formulation. Whatever the pasta, a general strengthening of its structure, a 33% to 47% increase in covalently linked proteins and a higher β-sheet structure were observed. However, these structural differences were evened out after the pasta was cooked, resulting in identical protein digestibility in LT and VHT pasta. Even after VHT drying, F-pasta had the best amino acid profile with the highest protein digestibility, proof of its nutritional interest.

  3. Hepatitis C virus infection protein network.

    Science.gov (United States)

    de Chassey, B; Navratil, V; Tafforeau, L; Hiet, M S; Aublin-Gex, A; Agaugué, S; Meiffren, G; Pradezynski, F; Faria, B F; Chantier, T; Le Breton, M; Pellet, J; Davoust, N; Mangeot, P E; Chaboud, A; Penin, F; Jacob, Y; Vidalain, P O; Vidal, M; André, P; Rabourdin-Combe, C; Lotteau, V

    2008-01-01

    A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein-protein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFbeta pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins.

  4. The Evolution of Reputation-Based Cooperation in Regular Networks

    Directory of Open Access Journals (Sweden)

    Tatsuya Sasaki

    2017-01-01

    Full Text Available Despite recent advances in reputation technologies, it is not clear how reputation systems can affect human cooperation in social networks. Although it is known that two of the major mechanisms in the evolution of cooperation are spatial selection and reputation-based reciprocity, theoretical study of the interplay between both mechanisms remains almost uncharted. Here, we present a new individual-based model for the evolution of reciprocal cooperation between reputation and networks. We comparatively analyze four of the leading moral assessment rules—shunning, image scoring, stern judging, and simple standing—and base the model on the giving game in regular networks for Cooperators, Defectors, and Discriminators. Discriminators rely on a proper moral assessment rule. By using individual-based models, we show that the four assessment rules are differently characterized in terms of how cooperation evolves, depending on the benefit-to-cost ratio, the network-node degree, and the observation and error conditions. Our findings show that the most tolerant rule—simple standing—is the most robust among the four assessment rules in promoting cooperation in regular networks.

  5. Co-evolution of the brand effect and competitiveness in evolving networks

    Science.gov (United States)

    Guo, Jin-Li

    2014-07-01

    The principle that ‘the brand effect is attractive’ underlies the preferential attachment. Here we show that the brand effect is just one dimension of attractiveness. Another dimension is competitiveness. We firstly introduce a general framework that allows us to investigate the competitive aspect of real networks, instead of simply preferring popular nodes. Our model accurately describes the evolution of social and technological networks. The phenomenon that more competitive nodes become richer can help us to understand the evolution of many competitive systems in nature and society. In general, the paper provides an explicit analytical expression of degree distributions of the network. In particular, the model yields a nontrivial time evolution of nodes' properties and the scale-free behavior with exponents depending on the microscopic parameters characterizing the competition rules. Secondly, through theoretical analyses and numerical simulations, we reveal that our model has not only the universality for the homogeneous weighted network, but also the character for the heterogeneous weighted network. Thirdly, we also develop a model based on the profit-driven mechanism. It can better describe the observed phenomenon in enterprise cooperation networks. We show that the standard preferential attachment, the growing random graph, the initial attractiveness model, the fitness model, and weighted networks can all be seen as degenerate cases of our model.

  6. Optimal neural networks for protein-structure prediction

    International Nuclear Information System (INIS)

    Head-Gordon, T.; Stillinger, F.H.

    1993-01-01

    The successful application of neural-network algorithms for prediction of protein structure is stymied by three problem areas: the sparsity of the database of known protein structures, poorly devised network architectures which make the input-output mapping opaque, and a global optimization problem in the multiple-minima space of the network variables. We present a simplified polypeptide model residing in two dimensions with only two amino-acid types, A and B, which allows the determination of the global energy structure for all possible sequences of pentamer, hexamer, and heptamer lengths. This model simplicity allows us to compile a complete structural database and to devise neural networks that reproduce the tertiary structure of all sequences with absolute accuracy and with the smallest number of network variables. These optimal networks reveal that the three problem areas are convoluted, but that thoughtful network designs can actually deconvolute these detrimental traits to provide network algorithms that genuinely impact on the ability of the network to generalize or learn the desired mappings. Furthermore, the two-dimensional polypeptide model shows sufficient chemical complexity so that transfer of neural-network technology to more realistic three-dimensional proteins is evident

  7. Developmental evolution in social insects: regulatory networks from genes to societies.

    Science.gov (United States)

    Linksvayer, Timothy A; Fewell, Jennifer H; Gadau, Jürgen; Laubichler, Manfred D

    2012-05-01

    The evolution and development of complex phenotypes in social insect colonies, such as queen-worker dimorphism or division of labor, can, in our opinion, only be fully understood within an expanded mechanistic framework of Developmental Evolution. Conversely, social insects offer a fertile research area in which fundamental questions of Developmental Evolution can be addressed empirically. We review the concept of gene regulatory networks (GRNs) that aims to fully describe the battery of interacting genomic modules that are differentially expressed during the development of individual organisms. We discuss how distinct types of network models have been used to study different levels of biological organization in social insects, from GRNs to social networks. We propose that these hierarchical networks spanning different organizational levels from genes to societies should be integrated and incorporated into full GRN models to elucidate the evolutionary and developmental mechanisms underlying social insect phenotypes. Finally, we discuss prospects and approaches to achieve such an integration. © 2012 WILEY PERIODICALS, INC.

  8. Divergence, recombination and retention of functionality during protein evolution

    Directory of Open Access Journals (Sweden)

    Xu Yanlong O

    2005-09-01

    Full Text Available Abstract We have only a vague idea of precisely how protein sequences evolve in the context of protein structure and function. This is primarily because structural and functional contexts are not easily predictable from the primary sequence, and evaluating patterns of evolution at individual residue positions is also difficult. As a result of increasing biodiversity in genomics studies, progress is being made in detecting context-dependent variation in substitution processes, but it remains unclear exactly what context-dependent patterns we should be looking for. To address this, we have been simulating protein evolution in the context of structure and function using lattice models of proteins and ligands (or substrates. These simulations include thermodynamic features of protein stability and population dynamics. We refer to this approach as 'ab initio evolution' to emphasise the fact that the equilibrium details of fitness distributions arise from the physical principles of the system and not from any preconceived notions or arbitrary mathematical distributions. Here, we present results on the retention of functionality in homologous recombinants following population divergence. A central result is that protein structure characteristics can strongly influence recombinant functionality. Exceptional structures with many sequence options evolve quickly and tend to retain functionality -- even in highly diverged recombinants. By contrast, the more common structures with fewer sequence options evolve more slowly, but the fitness of recombinants drops off rapidly as homologous proteins diverge. These results have implications for understanding viral evolution, speciation and directed evolutionary experiments. Our analysis of the divergence process can also guide improved methods for accurately approximating folding probabilities in more complex but realistic systems.

  9. Protein complex prediction based on k-connected subgraphs in protein interaction network

    Directory of Open Access Journals (Sweden)

    Habibi Mahnaz

    2010-09-01

    Full Text Available Abstract Background Protein complexes play an important role in cellular mechanisms. Recently, several methods have been presented to predict protein complexes in a protein interaction network. In these methods, a protein complex is predicted as a dense subgraph of protein interactions. However, interactions data are incomplete and a protein complex does not have to be a complete or dense subgraph. Results We propose a more appropriate protein complex prediction method, CFA, that is based on connectivity number on subgraphs. We evaluate CFA using several protein interaction networks on reference protein complexes in two benchmark data sets (MIPS and Aloy, containing 1142 and 61 known complexes respectively. We compare CFA to some existing protein complex prediction methods (CMC, MCL, PCP and RNSC in terms of recall and precision. We show that CFA predicts more complexes correctly at a competitive level of precision. Conclusions Many real complexes with different connectivity level in protein interaction network can be predicted based on connectivity number. Our CFA program and results are freely available from http://www.bioinf.cs.ipm.ir/softwares/cfa/CFA.rar.

  10. Evolution of weighted complex bus transit networks with flow

    Science.gov (United States)

    Huang, Ailing; Xiong, Jie; Shen, Jinsheng; Guan, Wei

    2016-02-01

    Study on the intrinsic properties and evolutional mechanism of urban public transit networks (PTNs) has great significance for transit planning and control, particularly considering passengers’ dynamic behaviors. This paper presents an empirical analysis for exploring the complex properties of Beijing’s weighted bus transit network (BTN) based on passenger flow in L-space, and proposes a bi-level evolution model to simulate the development of transit routes from the view of complex network. The model is an iterative process that is driven by passengers’ travel demands and dual-controlled interest mechanism, which is composed of passengers’ spatio-temporal requirements and cost constraint of transit agencies. Also, the flow’s dynamic behaviors, including the evolutions of travel demand, sectional flow attracted by a new link and flow perturbation triggered in nearby routes, are taken into consideration in the evolutional process. We present the numerical experiment to validate the model, where the main parameters are estimated by using distribution functions that are deduced from real-world data. The results obtained have proven that our model can generate a BTN with complex properties, such as the scale-free behavior or small-world phenomenon, which shows an agreement with our empirical results. Our study’s results can be exploited to optimize the real BTN’s structure and improve the network’s robustness.

  11. Parallel or convergent evolution in human population genomic data revealed by genotype networks.

    Science.gov (United States)

    R Vahdati, Ali; Wagner, Andreas

    2016-08-02

    Genotype networks are representations of genetic variation data that are complementary to phylogenetic trees. A genotype network is a graph whose nodes are genotypes (DNA sequences) with the same broadly defined phenotype. Two nodes are connected if they differ in some minimal way, e.g., in a single nucleotide. We analyze human genome variation data from the 1,000 genomes project, and construct haploid genotype (haplotype) networks for 12,235 protein coding genes. The structure of these networks varies widely among genes, indicating different patterns of variation despite a shared evolutionary history. We focus on those genes whose genotype networks show many cycles, which can indicate homoplasy, i.e., parallel or convergent evolution, on the sequence level. For 42 genes, the observed number of cycles is so large that it cannot be explained by either chance homoplasy or recombination. When analyzing possible explanations, we discovered evidence for positive selection in 21 of these genes and, in addition, a potential role for constrained variation and purifying selection. Balancing selection plays at most a small role. The 42 genes with excess cycles are enriched in functions related to immunity and response to pathogens. Genotype networks are representations of genetic variation data that can help understand unusual patterns of genomic variation.

  12. Positive Selection and Centrality in the Yeast and Fly Protein-Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Sandip Chakraborty

    2016-01-01

    Full Text Available Proteins within a molecular network are expected to be subject to different selective pressures depending on their relative hierarchical positions. However, it is not obvious what genes within a network should be more likely to evolve under positive selection. On one hand, only mutations at genes with a relatively high degree of control over adaptive phenotypes (such as those encoding highly connected proteins are expected to be “seen” by natural selection. On the other hand, a high degree of pleiotropy at these genes is expected to hinder adaptation. Previous analyses of the human protein-protein interaction network have shown that genes under long-term, recurrent positive selection (as inferred from interspecific comparisons tend to act at the periphery of the network. It is unknown, however, whether these trends apply to other organisms. Here, we show that long-term positive selection has preferentially targeted the periphery of the yeast interactome. Conversely, in flies, genes under positive selection encode significantly more connected and central proteins. These observations are not due to covariation of genes’ adaptability and centrality with confounding factors. Therefore, the distribution of proteins encoded by genes under recurrent positive selection across protein-protein interaction networks varies from one species to another.

  13. Fitness-driven deactivation in network evolution

    International Nuclear Information System (INIS)

    Xu, Xin-Jian; Peng, Xiao-Long; Fu, Xin-Chu; Small, Michael

    2010-01-01

    Individual nodes in evolving real-world networks typically experience growth and decay—that is, the popularity and influence of individuals peaks and then fades. In this paper, we study this phenomenon via an intrinsic nodal fitness function and an intuitive ageing mechanism. Each node of the network is endowed with a fitness which represents its activity. All the nodes have two discrete stages: active and inactive. The evolution of the network combines the addition of new active nodes randomly connected to existing active ones and the deactivation of old active nodes with a possibility inversely proportional to their fitnesses. We obtain a structured exponential network when the fitness distribution of the individuals is homogeneous and a structured scale-free network with heterogeneous fitness distributions. Furthermore, we recover two universal scaling laws of the clustering coefficient for both cases, C(k) ∼ k −1 and C ∼ n −1 , where k and n refer to the node degree and the number of active individuals, respectively. These results offer a new simple description of the growth and ageing of networks where intrinsic features of individual nodes drive their popularity, and hence degree

  14. Context-specific protein network miner - an online system for exploring context-specific protein interaction networks from the literature

    KAUST Repository

    Chowdhary, Rajesh

    2012-04-06

    Background: Protein interaction networks (PINs) specific within a particular context contain crucial information regarding many cellular biological processes. For example, PINs may include information on the type and directionality of interaction (e.g. phosphorylation), location of interaction (i.e. tissues, cells), and related diseases. Currently, very few tools are capable of deriving context-specific PINs for conducting exploratory analysis. Results: We developed a literature-based online system, Context-specific Protein Network Miner (CPNM), which derives context-specific PINs in real-time from the PubMed database based on a set of user-input keywords and enhanced PubMed query system. CPNM reports enriched information on protein interactions (with type and directionality), their network topology with summary statistics (e.g. most densely connected proteins in the network; most densely connected protein-pairs; and proteins connected by most inbound/outbound links) that can be explored via a user-friendly interface. Some of the novel features of the CPNM system include PIN generation, ontology-based PubMed query enhancement, real-time, user-queried, up-to-date PubMed document processing, and prediction of PIN directionality. Conclusions: CPNM provides a tool for biologists to explore PINs. It is freely accessible at http://www.biotextminer.com/CPNM/. © 2012 Chowdhary et al.

  15. Context-specific protein network miner - an online system for exploring context-specific protein interaction networks from the literature

    KAUST Repository

    Chowdhary, Rajesh; Tan, Sin Lam; Zhang, Jinfeng; Karnik, Shreyas; Bajic, Vladimir B.; Liu, Jun S.

    2012-01-01

    Background: Protein interaction networks (PINs) specific within a particular context contain crucial information regarding many cellular biological processes. For example, PINs may include information on the type and directionality of interaction (e.g. phosphorylation), location of interaction (i.e. tissues, cells), and related diseases. Currently, very few tools are capable of deriving context-specific PINs for conducting exploratory analysis. Results: We developed a literature-based online system, Context-specific Protein Network Miner (CPNM), which derives context-specific PINs in real-time from the PubMed database based on a set of user-input keywords and enhanced PubMed query system. CPNM reports enriched information on protein interactions (with type and directionality), their network topology with summary statistics (e.g. most densely connected proteins in the network; most densely connected protein-pairs; and proteins connected by most inbound/outbound links) that can be explored via a user-friendly interface. Some of the novel features of the CPNM system include PIN generation, ontology-based PubMed query enhancement, real-time, user-queried, up-to-date PubMed document processing, and prediction of PIN directionality. Conclusions: CPNM provides a tool for biologists to explore PINs. It is freely accessible at http://www.biotextminer.com/CPNM/. © 2012 Chowdhary et al.

  16. Functional evolution of new and expanded attention networks in humans.

    Science.gov (United States)

    Patel, Gaurav H; Yang, Danica; Jamerson, Emery C; Snyder, Lawrence H; Corbetta, Maurizio; Ferrera, Vincent P

    2015-07-28

    Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.

  17. An approach of community evolution based on gravitational relationship refactoring in dynamic networks

    International Nuclear Information System (INIS)

    Yin, Guisheng; Chi, Kuo; Dong, Yuxin; Dong, Hongbin

    2017-01-01

    In this paper, an approach of community evolution based on gravitational relationship refactoring between the nodes in a dynamic network is proposed, and it can be used to simulate the process of community evolution. A static community detection algorithm and a dynamic community evolution algorithm are included in the approach. At first, communities are initialized by constructing the core nodes chains, the nodes can be iteratively searched and divided into corresponding communities via the static community detection algorithm. For a dynamic network, an evolutionary process is divided into three phases, and behaviors of community evolution can be judged according to the changing situation of the core nodes chain in each community. Experiments show that the proposed approach can achieve accuracy and availability in the synthetic and real world networks. - Highlights: • The proposed approach considers both the static community detection and dynamic community evolution. • The approach of community evolution can identify the whole 6 common evolution events. • The proposed approach can judge the evolutionary events according to the variations of the core nodes chains.

  18. Co-evolution of the brand effect and competitiveness in evolving networks

    International Nuclear Information System (INIS)

    Guo Jin-Li

    2014-01-01

    The principle that ‘the brand effect is attractive’ underlies the preferential attachment. Here we show that the brand effect is just one dimension of attractiveness. Another dimension is competitiveness. We firstly introduce a general framework that allows us to investigate the competitive aspect of real networks, instead of simply preferring popular nodes. Our model accurately describes the evolution of social and technological networks. The phenomenon that more competitive nodes become richer can help us to understand the evolution of many competitive systems in nature and society. In general, the paper provides an explicit analytical expression of degree distributions of the network. In particular, the model yields a nontrivial time evolution of nodes' properties and the scale-free behavior with exponents depending on the microscopic parameters characterizing the competition rules. Secondly, through theoretical analyses and numerical simulations, we reveal that our model has not only the universality for the homogeneous weighted network, but also the character for the heterogeneous weighted network. Thirdly, we also develop a model based on the profit-driven mechanism. It can better describe the observed phenomenon in enterprise cooperation networks. We show that the standard preferential attachment, the growing random graph, the initial attractiveness model, the fitness model, and weighted networks can all be seen as degenerate cases of our model. (general)

  19. Comparative Study of Elastic Network Model and Protein Contact Network for Protein Complexes: The Hemoglobin Case

    Directory of Open Access Journals (Sweden)

    Guang Hu

    2017-01-01

    Full Text Available The overall topology and interfacial interactions play key roles in understanding structural and functional principles of protein complexes. Elastic Network Model (ENM and Protein Contact Network (PCN are two widely used methods for high throughput investigation of structures and interactions within protein complexes. In this work, the comparative analysis of ENM and PCN relative to hemoglobin (Hb was taken as case study. We examine four types of structural and dynamical paradigms, namely, conformational change between different states of Hbs, modular analysis, allosteric mechanisms studies, and interface characterization of an Hb. The comparative study shows that ENM has an advantage in studying dynamical properties and protein-protein interfaces, while PCN is better for describing protein structures quantitatively both from local and from global levels. We suggest that the integration of ENM and PCN would give a potential but powerful tool in structural systems biology.

  20. Unveiling protein functions through the dynamics of the interaction network.

    Directory of Open Access Journals (Sweden)

    Irene Sendiña-Nadal

    Full Text Available Protein interaction networks have become a tool to study biological processes, either for predicting molecular functions or for designing proper new drugs to regulate the main biological interactions. Furthermore, such networks are known to be organized in sub-networks of proteins contributing to the same cellular function. However, the protein function prediction is not accurate and each protein has traditionally been assigned to only one function by the network formalism. By considering the network of the physical interactions between proteins of the yeast together with a manual and single functional classification scheme, we introduce a method able to reveal important information on protein function, at both micro- and macro-scale. In particular, the inspection of the properties of oscillatory dynamics on top of the protein interaction network leads to the identification of misclassification problems in protein function assignments, as well as to unveil correct identification of protein functions. We also demonstrate that our approach can give a network representation of the meta-organization of biological processes by unraveling the interactions between different functional classes.

  1. A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network

    Directory of Open Access Journals (Sweden)

    De Graaf David

    2007-07-01

    Full Text Available Abstract Background The nuclear receptors are a large family of eukaryotic transcription factors that constitute major pharmacological targets. They exert their combinatorial control through homotypic heterodimerisation. Elucidation of this dimerisation network is vital in order to understand the complex dynamics and potential cross-talk involved. Results Phylogeny, protein-protein interactions, protein-DNA interactions and gene expression data have been integrated to provide a comprehensive and up-to-date description of the topology and properties of the nuclear receptor interaction network in humans. We discriminate between DNA-binding and non-DNA-binding dimers, and provide a comprehensive interaction map, that identifies potential cross-talk between the various pathways of nuclear receptors. Conclusion We infer that the topology of this network is hub-based, and much more connected than previously thought. The hub-based topology of the network and the wide tissue expression pattern of NRs create a highly competitive environment for the common heterodimerising partners. Furthermore, a significant number of negative feedback loops is present, with the hub protein SHP [NR0B2] playing a major role. We also compare the evolution, topology and properties of the nuclear receptor network with the hub-based dimerisation network of the bHLH transcription factors in order to identify both unique themes and ubiquitous properties in gene regulation. In terms of methodology, we conclude that such a comprehensive picture can only be assembled by semi-automated text-mining, manual curation and integration of data from various sources.

  2. US long distance fiber optic networks: Technology, evolution and advanced concepts. Volume 3: Advanced networks and economics

    Science.gov (United States)

    1986-10-01

    This study projects until 2000 the evolution of long distance fiber optic networks in the U.S. Volume 1 is the executive Summary. Volume 2 focuses on fiber optic components and systems that are directly related to the operation of long-haul networks. Optimistic, pessimistic and most likely scenarios of technology development are presented. The activities of national and regional companies implementing fiber long haul networks are also highlighted, along with an analysis of the market and regulatory forces affecting network evolution. Volume 3 presents advanced fiber optic network concept definitions. Inter-LATA traffic is quantified and forms the basis for the construction of 11-, 15-, 17-, and 23-node networks. Using the technology projections from Volume 2, a financial model identifies cost drivers and determines circuit mile costs between any two LATAs. A comparison of fiber optics with alternative transmission concludes the report.

  3. Aggregation and network formation in self-assembly of protein (H3.1) by a coarse-grained Monte Carlo simulation

    Science.gov (United States)

    Pandey, R. B.; Farmer, B. L.

    2014-11-01

    Multi-scale aggregation to network formation of interacting proteins (H3.1) are examined by a knowledge-based coarse-grained Monte Carlo simulation as a function of temperature and the number of protein chains, i.e., the concentration of the protein. Self-assembly of corresponding homo-polymers of constitutive residues (Cys, Thr, and Glu) with extreme residue-residue interactions, i.e., attractive (Cys-Cys), neutral (Thr-Thr), and repulsive (Glu-Glu), are also studied for comparison with the native protein. Visual inspections show contrast and similarity in morphological evolutions of protein assembly, aggregation of small aggregates to a ramified network from low to high temperature with the aggregation of a Cys-polymer, and an entangled network of Glu and Thr polymers. Variations in mobility profiles of residues with the concentration of the protein suggest that the segmental characteristic of proteins is altered considerably by the self-assembly from that in its isolated state. The global motion of proteins and Cys polymer chains is enhanced by their interacting network at the low temperature where isolated chains remain quasi-static. Transition from globular to random coil transition, evidenced by the sharp variation in the radius of gyration, of an isolated protein is smeared due to self-assembly of interacting networks of many proteins. Scaling of the structure factor S(q) with the wave vector q provides estimates of effective dimension D of the mass distribution at multiple length scales in self-assembly. Crossover from solid aggregates (D ˜ 3) at low temperature to a ramified fibrous network (D ˜ 2) at high temperature is observed for the protein H3.1 and Cys polymers in contrast to little changes in mass distribution (D ˜ 1.6) of fibrous Glu- and Thr-chain configurations.

  4. Constraints and entropy in a model of network evolution

    Science.gov (United States)

    Tee, Philip; Wakeman, Ian; Parisis, George; Dawes, Jonathan; Kiss, István Z.

    2017-11-01

    Barabási-Albert's "Scale Free" model is the starting point for much of the accepted theory of the evolution of real world communication networks. Careful comparison of the theory with a wide range of real world networks, however, indicates that the model is in some cases, only a rough approximation to the dynamical evolution of real networks. In particular, the exponent γ of the power law distribution of degree is predicted by the model to be exactly 3, whereas in a number of real world networks it has values between 1.2 and 2.9. In addition, the degree distributions of real networks exhibit cut offs at high node degree, which indicates the existence of maximal node degrees for these networks. In this paper we propose a simple extension to the "Scale Free" model, which offers better agreement with the experimental data. This improvement is satisfying, but the model still does not explain why the attachment probabilities should favor high degree nodes, or indeed how constraints arrive in non-physical networks. Using recent advances in the analysis of the entropy of graphs at the node level we propose a first principles derivation for the "Scale Free" and "constraints" model from thermodynamic principles, and demonstrate that both preferential attachment and constraints could arise as a natural consequence of the second law of thermodynamics.

  5. Protein splicing and its evolution in eukaryotes

    Directory of Open Access Journals (Sweden)

    Starokadomskyy P. L.

    2010-02-01

    Full Text Available Inteins, or protein introns, are parts of protein sequences that are post-translationally excised, their flanking regions (exteins being spliced together. This process was called protein splicing. Originally inteins were found in prokaryotic or unicellular eukaryotic organisms. But the general principles of post-translation protein rearrangement are evolving yielding different post-translation modification of proteins in multicellular organisms. For clarity, these non-intein mediated events call either protein rearrangements or protein editing. The most intriguing example of protein editing is proteasome-mediated splicing of antigens in vertebrates that may play important role in antigen presentation. Other examples of protein rearrangements are maturation of Hg-proteins (critical receptors in embryogenesis as well as maturation of several metabolic enzymes. Despite a lack of experimental data we try to analyze some intriguing examples of protein splicing evolution.

  6. Detection of Locally Over-Represented GO Terms in Protein-Protein Interaction Networks

    Science.gov (United States)

    LAVALLÉE-ADAM, MATHIEU; COULOMBE, BENOIT; BLANCHETTE, MATHIEU

    2015-01-01

    High-throughput methods for identifying protein-protein interactions produce increasingly complex and intricate interaction networks. These networks are extremely rich in information, but extracting biologically meaningful hypotheses from them and representing them in a human-readable manner is challenging. We propose a method to identify Gene Ontology terms that are locally over-represented in a subnetwork of a given biological network. Specifically, we propose several methods to evaluate the degree of clustering of proteins associated to a particular GO term in both weighted and unweighted PPI networks, and describe efficient methods to estimate the statistical significance of the observed clustering. We show, using Monte Carlo simulations, that our best approximation methods accurately estimate the true p-value, for random scale-free graphs as well as for actual yeast and human networks. When applied to these two biological networks, our approach recovers many known complexes and pathways, but also suggests potential functions for many subnetworks. Online Supplementary Material is available at www.liebertonline.com. PMID:20377456

  7. Modeling evolution of crosstalk in noisy signal transduction networks

    Science.gov (United States)

    Tareen, Ammar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

    2018-02-01

    Signal transduction networks can form highly interconnected systems within cells due to crosstalk between constituent pathways. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk for two parallel signaling pathways that arise via gene duplication. We use a sequence-based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. We find that one fitness function leads to a high degree of crosstalk while the other leads to pathway specificity. Our results offer insights on the relationship between network architecture and information transmission for noisy biomolecular networks.

  8. Molecular evolution of cyclin proteins in animals and fungi

    Directory of Open Access Journals (Sweden)

    Afonnikov Dmitry A

    2011-07-01

    Full Text Available Abstract Background The passage through the cell cycle is controlled by complexes of cyclins, the regulatory units, with cyclin-dependent kinases, the catalytic units. It is also known that cyclins form several families, which differ considerably in primary structure from one eukaryotic organism to another. Despite these lines of evidence, the relationship between the evolution of cyclins and their function is an open issue. Here we present the results of our study on the molecular evolution of A-, B-, D-, E-type cyclin proteins in animals and fungi. Results We constructed phylogenetic trees for these proteins, their ancestral sequences and analyzed patterns of amino acid replacements. The analysis of infrequently fixed atypical amino acid replacements in cyclins evidenced that accelerated evolution proceeded predominantly during paralog duplication or after it in animals and fungi and that it was related to aromorphic changes in animals. It was shown also that evolutionary flexibility of cyclin function may be provided by consequential reorganization of regions on protein surface remote from CDK binding sites in animal and fungal cyclins and by functional differentiation of paralogous cyclins formed in animal evolution. Conclusions The results suggested that changes in the number and/or nature of cyclin-binding proteins may underlie the evolutionary role of the alterations in the molecular structure of cyclins and their involvement in diverse molecular-genetic events.

  9. Protein Annotation from Protein Interaction Networks and Gene Ontology

    OpenAIRE

    Nguyen, Cao D.; Gardiner, Katheleen J.; Cios, Krzysztof J.

    2011-01-01

    We introduce a novel method for annotating protein function that combines Naïve Bayes and association rules, and takes advantage of the underlying topology in protein interaction networks and the structure of graphs in the Gene Ontology. We apply our method to proteins from the Human Protein Reference Database (HPRD) and show that, in comparison with other approaches, it predicts protein functions with significantly higher recall with no loss of precision. Specifically, it achieves 51% precis...

  10. Evolution of quantum and classical strategies on networks by group interactions

    International Nuclear Information System (INIS)

    Li Qiang; Chen Minyou; Iqbal, Azhar; Abbott, Derek

    2012-01-01

    In this paper, quantum strategies are introduced within evolutionary games in order to investigate the evolution of quantum and classical strategies on networks in the public goods game. Comparing the results of evolution on a scale-free network and a square lattice, we find that a quantum strategy outperforms the classical strategies, regardless of the network. Moreover, a quantum strategy dominates the population earlier in group interactions than it does in pairwise interactions. In particular, if the hub node in a scale-free network is occupied by a cooperator initially, the strategy of cooperation will prevail in the population. However, in other situations, a quantum strategy can defeat the classical ones and finally becomes the dominant strategy in the population. (paper)

  11. The Evolution of ICT Markets: An Agent-Based Model on Complex Networks

    Science.gov (United States)

    Zhao, Liangjie; Wu, Bangtao; Chen, Zhong; Li, Li

    Information and communication technology (ICT) products exhibit positive network effects.The dynamic process of ICT markets evolution has two intrinsic characteristics: (1) customers are influenced by each others’ purchasing decision; (2) customers are intelligent agents with bounded rationality.Guided by complex systems theory, we construct an agent-based model and simulate on complex networks to examine how the evolution can arise from the interaction of customers, which occur when they make expectations about the future installed base of a product by the fraction of neighbors who are using the same product in his personal network.We demonstrate that network effects play an important role in the evolution of markets share, which make even an inferior product can dominate the whole market.We also find that the intensity of customers’ communication can influence whether the best initial strategy for firms is to improve product quality or expand their installed base.

  12. Space evolution model and empirical analysis of an urban public transport network

    Science.gov (United States)

    Sui, Yi; Shao, Feng-jing; Sun, Ren-cheng; Li, Shu-jing

    2012-07-01

    This study explores the space evolution of an urban public transport network, using empirical evidence and a simulation model validated on that data. Public transport patterns primarily depend on traffic spatial-distribution, demands of passengers and expected utility of investors. Evolution is an iterative process of satisfying the needs of passengers and investors based on a given traffic spatial-distribution. The temporal change of urban public transport network is evaluated both using topological measures and spatial ones. The simulation model is validated using empirical data from nine big cities in China. Statistical analyses on topological and spatial attributes suggest that an evolution network with traffic demands characterized by power-law numerical values which distribute in a mode of concentric circles tallies well with these nine cities.

  13. Evidence of probabilistic behaviour in protein interaction networks

    Directory of Open Access Journals (Sweden)

    Reifman Jaques

    2008-01-01

    Full Text Available Abstract Background Data from high-throughput experiments of protein-protein interactions are commonly used to probe the nature of biological organization and extract functional relationships between sets of proteins. What has not been appreciated is that the underlying mechanisms involved in assembling these networks may exhibit considerable probabilistic behaviour. Results We find that the probability of an interaction between two proteins is generally proportional to the numerical product of their individual interacting partners, or degrees. The degree-weighted behaviour is manifested throughout the protein-protein interaction networks studied here, except for the high-degree, or hub, interaction areas. However, we find that the probabilities of interaction between the hubs are still high. Further evidence is provided by path length analyses, which show that these hubs are separated by very few links. Conclusion The results suggest that protein-protein interaction networks incorporate probabilistic elements that lead to scale-rich hierarchical architectures. These observations seem to be at odds with a biologically-guided organization. One interpretation of the findings is that we are witnessing the ability of proteins to indiscriminately bind rather than the protein-protein interactions that are actually utilized by the cell in biological processes. Therefore, the topological study of a degree-weighted network requires a more refined methodology to extract biological information about pathways, modules, or other inferred relationships among proteins.

  14. Social dilemmas in an online social network: The structure and evolution of cooperation

    International Nuclear Information System (INIS)

    Fu Feng; Chen Xiaojie; Liu Lianghuan; Wang Long

    2007-01-01

    We investigate two paradigms for studying the evolution of cooperation-Prisoner's Dilemma and Snowdrift game in an online friendship network, obtained from a social networking site. By structural analysis, it is revealed that the empirical social network has small-world and scale-free properties. Besides, it exhibits assortative mixing pattern. Then, we study the evolutionary version of the two types of games on it. It is found that cooperation is substantially promoted with small values of game matrix parameters in both games. Whereas the competent cooperators induced by the underlying network of contacts will be dramatically inhibited with increasing values of the game parameters. Further, we explore the role of assortativity in evolution of cooperation by random edge rewiring. We find that increasing amount of assortativity will to a certain extent diminish the cooperation level. We also show that connected large hubs are capable of maintaining cooperation. The evolution of cooperation on empirical networks is influenced by various network effects in a combined manner, compared with that on model networks. Our results can help understand the cooperative behaviors in human groups and society

  15. A random walk evolution model of wireless sensor networks and virus spreading

    International Nuclear Information System (INIS)

    Wang Ya-Qi; Yang Xiao-Yuan

    2013-01-01

    In this paper, considering both cluster heads and sensor nodes, we propose a novel evolving a network model based on a random walk to study the fault tolerance decrease of wireless sensor networks (WSNs) due to node failure, and discuss the spreading dynamic behavior of viruses in the evolution model. A theoretical analysis shows that the WSN generated by such an evolution model not only has a strong fault tolerance, but also can dynamically balance the energy loss of the entire network. It is also found that although the increase of the density of cluster heads in the network reduces the network efficiency, it can effectively inhibit the spread of viruses. In addition, the heterogeneity of the network improves the network efficiency and enhances the virus prevalence. We confirm all the theoretical results with sufficient numerical simulations. (general)

  16. Practical aspects of protein co-evolution.

    Science.gov (United States)

    Ochoa, David; Pazos, Florencio

    2014-01-01

    Co-evolution is a fundamental aspect of Evolutionary Theory. At the molecular level, co-evolutionary linkages between protein families have been used as indicators of protein interactions and functional relationships from long ago. Due to the complexity of the problem and the amount of genomic data required for these approaches to achieve good performances, it took a relatively long time from the appearance of the first ideas and concepts to the quotidian application of these approaches and their incorporation to the standard toolboxes of bioinformaticians and molecular biologists. Today, these methodologies are mature (both in terms of performance and usability/implementation), and the genomic information that feeds them large enough to allow their general application. This review tries to summarize the current landscape of co-evolution-based methodologies, with a strong emphasis on describing interesting cases where their application to important biological systems, alone or in combination with other computational and experimental approaches, allowed getting new insight into these.

  17. Gene Prioritization by Integrated Analysis of Protein Structural and Network Topological Properties for the Protein-Protein Interaction Network of Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Yashna Paul

    2016-01-01

    Full Text Available Neurological disorders are known to show similar phenotypic manifestations like anxiety, depression, and cognitive impairment. There is a need to identify shared genetic markers and molecular pathways in these diseases, which lead to such comorbid conditions. Our study aims to prioritize novel genetic markers that might increase the susceptibility of patients affected with one neurological disorder to other diseases with similar manifestations. Identification of pathways involving common candidate markers will help in the development of improved diagnosis and treatments strategies for patients affected with neurological disorders. This systems biology study for the first time integratively uses 3D-structural protein interface descriptors and network topological properties that characterize proteins in a neurological protein interaction network, to aid the identification of genes that are previously not known to be shared between these diseases. Results of protein prioritization by machine learning have identified known as well as new genetic markers which might have direct or indirect involvement in several neurological disorders. Important gene hubs have also been identified that provide an evidence for shared molecular pathways in the neurological disease network.

  18. Construction and analysis of protein-protein interaction networks based on proteomics data of prostate cancer

    Science.gov (United States)

    CHEN, CHEN; SHEN, HONG; ZHANG, LI-GUO; LIU, JIAN; CAO, XIAO-GE; YAO, AN-LIANG; KANG, SHAO-SAN; GAO, WEI-XING; HAN, HUI; CAO, FENG-HONG; LI, ZHI-GUO

    2016-01-01

    Currently, using human prostate cancer (PCa) tissue samples to conduct proteomics research has generated a large amount of data; however, only a very small amount has been thoroughly investigated. In this study, we manually carried out the mining of the full text of proteomics literature that involved comparisons between PCa and normal or benign tissue and identified 41 differentially expressed proteins verified or reported more than 2 times from different research studies. We regarded these proteins as seed proteins to construct a protein-protein interaction (PPI) network. The extended network included one giant network, which consisted of 1,264 nodes connected via 1,744 edges, and 3 small separate components. The backbone network was then constructed, which was derived from key nodes and the subnetwork consisting of the shortest path between seed proteins. Topological analyses of these networks were conducted to identify proteins essential for the genesis of PCa. Solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4) had the highest closeness centrality located in the center of each network, and the highest betweenness centrality and largest degree in the backbone network. Tubulin, beta 2C (TUBB2C) had the largest degree in the giant network and subnetwork. In addition, using module analysis of the whole PPI network, we obtained a densely connected region. Functional annotation indicated that the Ras protein signal transduction biological process, mitogen-activated protein kinase (MAPK), neurotrophin and the gonadotropin-releasing hormone (GnRH) signaling pathway may play an important role in the genesis and development of PCa. Further investigation of the SLC2A4, TUBB2C proteins, and these biological processes and pathways may therefore provide a potential target for the diagnosis and treatment of PCa. PMID:27121963

  19. Topological properties of complex networks in protein structures

    Science.gov (United States)

    Kim, Kyungsik; Jung, Jae-Won; Min, Seungsik

    2014-03-01

    We study topological properties of networks in structural classification of proteins. We model the native-state protein structure as a network made of its constituent amino-acids and their interactions. We treat four structural classes of proteins composed predominantly of α helices and β sheets and consider several proteins from each of these classes whose sizes range from amino acids of the Protein Data Bank. Particularly, we simulate and analyze the network metrics such as the mean degree, the probability distribution of degree, the clustering coefficient, the characteristic path length, the local efficiency, and the cost. This work was supported by the KMAR and DP under Grant WISE project (153-3100-3133-302-350).

  20. Energy Efficient Evolution of Mobile Broadband Networks

    DEFF Research Database (Denmark)

    Micallef, Gilbert

    to public commitments for reducing their energy and carbon footprint. In 2008 Vodafone stated that by the year 2020, efforts for reducing emissions are expected to halve emissions registered in the year 2006/7. In addition to presenting a more environmentally conscious brand, this is also hoped to reduce...... for mobile network operators to upgrade existing infrastructure different options are available. Irrespective of the selected option, capacity upgrades are bound to increase the power consumption of the network. Carried through case studies, a first analysis compares a number of network evolution strategies......, determining which provides the necessary performance while limiting the increase in power consumption. Overall, it is noted that a hybrid solution involving the upgrade of existing macro base station sites together with the deployment of outdoor or indoor small cells (heterogeneous network) provide the best...

  1. Emergence of fractal scale-free networks from stochastic evolution on the Cayley tree

    Energy Technology Data Exchange (ETDEWEB)

    Chełminiak, Przemysław, E-mail: geronimo@amu.edu.pl

    2013-11-29

    An unexpected recognition of fractal topology in some real-world scale-free networks has evoked again an interest in the mechanisms stimulating their evolution. To explain this phenomenon a few models of a deterministic construction as well as a probabilistic growth controlled by a tunable parameter have been proposed so far. A quite different approach based on the fully stochastic evolution of the fractal scale-free networks presented in this Letter counterpoises these former ideas. It is argued that the diffusive evolution of the network on the Cayley tree shapes its fractality, self-similarity and the branching number criticality without any control parameter. The last attribute of the scale-free network is an intrinsic property of the skeleton, a special type of spanning tree which determines its fractality.

  2. P-Finder: Reconstruction of Signaling Networks from Protein-Protein Interactions and GO Annotations.

    Science.gov (United States)

    Young-Rae Cho; Yanan Xin; Speegle, Greg

    2015-01-01

    Because most complex genetic diseases are caused by defects of cell signaling, illuminating a signaling cascade is essential for understanding their mechanisms. We present three novel computational algorithms to reconstruct signaling networks between a starting protein and an ending protein using genome-wide protein-protein interaction (PPI) networks and gene ontology (GO) annotation data. A signaling network is represented as a directed acyclic graph in a merged form of multiple linear pathways. An advanced semantic similarity metric is applied for weighting PPIs as the preprocessing of all three methods. The first algorithm repeatedly extends the list of nodes based on path frequency towards an ending protein. The second algorithm repeatedly appends edges based on the occurrence of network motifs which indicate the link patterns more frequently appearing in a PPI network than in a random graph. The last algorithm uses the information propagation technique which iteratively updates edge orientations based on the path strength and merges the selected directed edges. Our experimental results demonstrate that the proposed algorithms achieve higher accuracy than previous methods when they are tested on well-studied pathways of S. cerevisiae. Furthermore, we introduce an interactive web application tool, called P-Finder, to visualize reconstructed signaling networks.

  3. Experimental Evolution of a Green Fluorescent Protein Composed of 19 Unique Amino Acids without Tryptophan

    Science.gov (United States)

    Kawahara-Kobayashi, Akio; Hitotsuyanagi, Mitsuhiro; Amikura, Kazuaki; Kiga, Daisuke

    2014-04-01

    At some stage of evolution, genes of organisms may have encoded proteins that were synthesized using fewer than 20 unique amino acids. Similar to evolution of the natural 19-amino-acid proteins GroEL/ES, proteins composed of 19 unique amino acids would have been able to evolve by accumulating beneficial mutations within the 19-amino-acid repertoire encoded in an ancestral genetic code. Because Trp is thought to be the last amino acid included in the canonical 20-amino-acid repertoire, this late stage of protein evolution could be mimicked by experimental evolution of 19-amino-acid proteins without tryptophan (Trp). To further understand the evolution of proteins, we tried to mimic the evolution of a 19-amino-acid protein involving the accumulation of beneficial mutations using directed evolution by random mutagenesis on the whole targeted gene sequence. We created active 19-amino-acid green fluorescent proteins (GFPs) without Trp from a poorly fluorescent 19-amino-acid mutant, S1-W57F, by using directed evolution with two rounds of mutagenesis and selection. The N105I and S205T mutations showed beneficial effects on the S1-W57F mutant. When these two mutations were combined on S1-W57F, we observed an additive effect on the fluorescence intensity. In contrast, these mutations showed no clear improvement individually or in combination on GFPS1, which is the parental GFP mutant composed of 20 amino acids. Our results provide an additional example for the experimental evolution of 19-amino-acid proteins without Trp, and would help understand the mechanisms underlying the evolution of 19-amino-acid proteins. (236 words)

  4. Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

    Science.gov (United States)

    Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

    2015-11-01

    Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

  5. Topology-function conservation in protein-protein interaction networks.

    Science.gov (United States)

    Davis, Darren; Yaveroğlu, Ömer Nebil; Malod-Dognin, Noël; Stojmirovic, Aleksandar; Pržulj, Nataša

    2015-05-15

    Proteins underlay the functioning of a cell and the wiring of proteins in protein-protein interaction network (PIN) relates to their biological functions. Proteins with similar wiring in the PIN (topology around them) have been shown to have similar functions. This property has been successfully exploited for predicting protein functions. Topological similarity is also used to guide network alignment algorithms that find similarly wired proteins between PINs of different species; these similarities are used to transfer annotation across PINs, e.g. from model organisms to human. To refine these functional predictions and annotation transfers, we need to gain insight into the variability of the topology-function relationships. For example, a function may be significantly associated with specific topologies, while another function may be weakly associated with several different topologies. Also, the topology-function relationships may differ between different species. To improve our understanding of topology-function relationships and of their conservation among species, we develop a statistical framework that is built upon canonical correlation analysis. Using the graphlet degrees to represent the wiring around proteins in PINs and gene ontology (GO) annotations to describe their functions, our framework: (i) characterizes statistically significant topology-function relationships in a given species, and (ii) uncovers the functions that have conserved topology in PINs of different species, which we term topologically orthologous functions. We apply our framework to PINs of yeast and human, identifying seven biological process and two cellular component GO terms to be topologically orthologous for the two organisms. © The Author 2015. Published by Oxford University Press.

  6. Phylogeny and evolution of Rab7 and Rab9 proteins

    Directory of Open Access Journals (Sweden)

    Wyroba Elżbieta

    2009-05-01

    Full Text Available Abstract Background An important role in the evolution of intracellular trafficking machinery in eukaryotes played small GTPases belonging to the Rab family known as pivotal regulators of vesicle docking, fusion and transport. The Rab family is very diversified and divided into several specialized subfamilies. We focused on the VII functional group comprising Rab7 and Rab9, two related subfamilies, and analysed 210 sequences of these proteins. Rab7 regulates traffic from early to late endosomes and from late endosome to vacuole/lysosome, whereas Rab9 participates in transport from late endosomes to the trans-Golgi network. Results Although Rab7 and Rab9 proteins are quite small and show heterogeneous rates of substitution in different lineages, we found a phylogenetic signal and inferred evolutionary relationships between them. Rab7 proteins evolved before radiation of main eukaryotic supergroups while Rab9 GTPases diverged from Rab7 before split of choanoflagellates and metazoans. Additional duplication of Rab9 and Rab7 proteins resulting in several isoforms occurred in the early evolution of vertebrates and next in teleost fishes and tetrapods. Three Rab7 lineages emerged before divergence of monocots and eudicots and subsequent duplications of Rab7 genes occurred in particular angiosperm clades. Interestingly, several Rab7 copies were identified in some representatives of excavates, ciliates and amoebozoans. The presence of many Rab copies is correlated with significant differences in their expression level. The diversification of analysed Rab subfamilies is also manifested by non-conserved sequences and structural features, many of which are involved in the interaction with regulators and effectors. Individual sites discriminating different subgroups of Rab7 and Rab9 GTPases have been identified. Conclusion Phylogenetic reconstructions of Rab7 and Rab9 proteins were performed by a variety of methods. These Rab GTPases show diversification

  7. Evolution of the Converged NGN Service Platforms Towards Future Networks

    NARCIS (Netherlands)

    Mikóczy, E.; Kotuliak, I.; Deventer, M.O. van

    2011-01-01

    This article presents a comparison of main characteristics of the Next Generation Networks (NGN) and Future Generation Internet (FGI). The aim is to discuss and compare two approaches to Future Networks (FN) and services: the evolution of NGN, and the revolutionary approach of a new FGI. We present

  8. Category theoretic analysis of hierarchical protein materials and social networks.

    Directory of Open Access Journals (Sweden)

    David I Spivak

    Full Text Available 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.

  9. CombiMotif: A new algorithm for network motifs discovery in protein-protein interaction networks

    Science.gov (United States)

    Luo, Jiawei; Li, Guanghui; Song, Dan; Liang, Cheng

    2014-12-01

    Discovering motifs in protein-protein interaction networks is becoming a current major challenge in computational biology, since the distribution of the number of network motifs can reveal significant systemic differences among species. However, this task can be computationally expensive because of the involvement of graph isomorphic detection. In this paper, we present a new algorithm (CombiMotif) that incorporates combinatorial techniques to count non-induced occurrences of subgraph topologies in the form of trees. The efficiency of our algorithm is demonstrated by comparing the obtained results with the current state-of-the art subgraph counting algorithms. We also show major differences between unicellular and multicellular organisms. The datasets and source code of CombiMotif are freely available upon request.

  10. Social dilemmas in an online social network: The structure and evolution of cooperation

    Energy Technology Data Exchange (ETDEWEB)

    Fu Feng [Center for Systems and Control, College of Engineering, Peking University, Beijing 100871 (China); Department of Industrial Engineering and Management, College of Engineering, Peking University, Beijing 100871 (China)], E-mail: fufeng@pku.edu.cn; Chen Xiaojie; Liu Lianghuan [Center for Systems and Control, College of Engineering, Peking University, Beijing 100871 (China); Department of Industrial Engineering and Management, College of Engineering, Peking University, Beijing 100871 (China); Wang Long [Center for Systems and Control, College of Engineering, Peking University, Beijing 100871 (China); Department of Industrial Engineering and Management, College of Engineering, Peking University, Beijing 100871 (China)], E-mail: longwang@pku.edu.cn

    2007-11-05

    We investigate two paradigms for studying the evolution of cooperation-Prisoner's Dilemma and Snowdrift game in an online friendship network, obtained from a social networking site. By structural analysis, it is revealed that the empirical social network has small-world and scale-free properties. Besides, it exhibits assortative mixing pattern. Then, we study the evolutionary version of the two types of games on it. It is found that cooperation is substantially promoted with small values of game matrix parameters in both games. Whereas the competent cooperators induced by the underlying network of contacts will be dramatically inhibited with increasing values of the game parameters. Further, we explore the role of assortativity in evolution of cooperation by random edge rewiring. We find that increasing amount of assortativity will to a certain extent diminish the cooperation level. We also show that connected large hubs are capable of maintaining cooperation. The evolution of cooperation on empirical networks is influenced by various network effects in a combined manner, compared with that on model networks. Our results can help understand the cooperative behaviors in human groups and society.

  11. Adaptive evolution of relish, a Drosophila NF-kappaB/IkappaB protein.

    OpenAIRE

    Begun, D J; Whitley, P

    2000-01-01

    NF-kappaB and IkappaB proteins have central roles in regulation of inflammation and innate immunity in mammals. Homologues of these proteins also play an important role in regulation of the Drosophila immune response. Here we present a molecular population genetic analysis of Relish, a Drosophila NF-kappaB/IkappaB protein, in Drosophila simulans and D. melanogaster. We find strong evidence for adaptive protein evolution in D. simulans, but not in D. melanogaster. The adaptive evolution appear...

  12. Modeling community succession and assembly: A novel method for network evolution

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2012-06-01

    Full Text Available The process of modeling community succession and assembly is in some sense a method for network evolution, as done by Barabasi and Albert (1999. It is also one of the methods to create a sample networkfrom the statistic network I proposed earlier. I think that the mechanism of network evolution supposed by Barabasi and Albert is most likely applicable to the natural phenomena with emergency property. For natural phenomena without emergency property, the present study indicated that a scale-free network may be produced through a new mechanism, i.e., whether the connection of a taxon x occurs, dependent on the type and property of taxon y (in particular, the degree of its direct correlation with x to be connected but not necessarily the existing number of connections of taxon y, as proposed in present study.

  13. Domain organizations of modular extracellular matrix proteins and their evolution.

    Science.gov (United States)

    Engel, J

    1996-11-01

    Multidomain proteins which are composed of modular units are a rather recent invention of evolution. Domains are defined as autonomously folding regions of a protein, and many of them are similar in sequence and structure, indicating common ancestry. Their modular nature is emphasized by frequent repetitions in identical or in different proteins and by a large number of different combinations with other domains. The extracellular matrix is perhaps the largest biological system composed of modular mosaic proteins, and its astonishing complexity and diversity are based on them. A cluster of minireviews on modular proteins is being published in Matrix Biology. These deal with the evolution of modular proteins, the three-dimensional structure of domains and the ways in which these interact in a multidomain protein. They discuss structure-function relationships in calcium binding domains, collagen helices, alpha-helical coiled-coil domains and C-lectins. The present minireview is focused on some general aspects and serves as an introduction to the cluster.

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Evolution of a protein folding nucleus.

    Science.gov (United States)

    Xia, Xue; Longo, Liam M; Sutherland, Mason A; Blaber, Michael

    2016-07-01

    The folding nucleus (FN) is a cryptic element within protein primary structure that enables an efficient folding pathway and is the postulated heritable element in the evolution of protein architecture; however, almost nothing is known regarding how the FN structurally changes as complex protein architecture evolves from simpler peptide motifs. We report characterization of the FN of a designed purely symmetric β-trefoil protein by ϕ-value analysis. We compare the structure and folding properties of key foldable intermediates along the evolutionary trajectory of the β-trefoil. The results show structural acquisition of the FN during gene fusion events, incorporating novel turn structure created by gene fusion. Furthermore, the FN is adjusted by circular permutation in response to destabilizing functional mutation. FN plasticity by way of circular permutation is made possible by the intrinsic C3 cyclic symmetry of the β-trefoil architecture, identifying a possible selective advantage that helps explain the prevalence of cyclic structural symmetry in the proteome. © 2015 The Protein Society.

  16. Cooperative behavior evolution of small groups on interconnected networks

    International Nuclear Information System (INIS)

    Huang, Keke; Cheng, Yuan; Zheng, Xiaoping; Yang, Yeqing

    2015-01-01

    Highlights: • Small groups are modeled on interconnected networks. • Players face different dilemmas inside and outside small groups. • Impact of the ratio and strength of link on the behavioral evolution are studied. - Abstract: Understanding the behavioral evolution in evacuation is significant for guiding and controlling the evacuation process. Based on the fact that the population consists of many small groups, here we model the small groups which are separated in space but linked by other methods, such as kinship, on interconnected networks. Namely, the players in the same layer belong to an identical small group, while the players located in different layers belong to different small groups. And the players of different layers establish interaction by edge crossed layers. In addition, players face different dilemmas inside and outside small groups, in detail, the players in the same layer play prisoner’s dilemma, but players in different layers play harmony game. By means of numerous simulations, we study the impact of the ratio and strength of link on the behavioral evolution. Because the framework of this work takes the space distribution into account, which is close to the realistic life, we hope that it can provide a new insight to reveal the law of behavioral evolution of evacuation population.

  17. The triple helix of collagens - an ancient protein structure that enabled animal multicellularity and tissue evolution.

    Science.gov (United States)

    Fidler, Aaron L; Boudko, Sergei P; Rokas, Antonis; Hudson, Billy G

    2018-04-09

    The cellular microenvironment, characterized by an extracellular matrix (ECM), played an essential role in the transition from unicellularity to multicellularity in animals (metazoans), and in the subsequent evolution of diverse animal tissues and organs. A major ECM component are members of the collagen superfamily -comprising 28 types in vertebrates - that exist in diverse supramolecular assemblies ranging from networks to fibrils. Each assembly is characterized by a hallmark feature, a protein structure called a triple helix. A current gap in knowledge is understanding the mechanisms of how the triple helix encodes and utilizes information in building scaffolds on the outside of cells. Type IV collagen, recently revealed as the evolutionarily most ancient member of the collagen superfamily, serves as an archetype for a fresh view of fundamental structural features of a triple helix that underlie the diversity of biological activities of collagens. In this Opinion, we argue that the triple helix is a protein structure of fundamental importance in building the extracellular matrix, which enabled animal multicellularity and tissue evolution. © 2018. Published by The Company of Biologists Ltd.

  18. Protein annotation from protein interaction networks and Gene Ontology.

    Science.gov (United States)

    Nguyen, Cao D; Gardiner, Katheleen J; Cios, Krzysztof J

    2011-10-01

    We introduce a novel method for annotating protein function that combines Naïve Bayes and association rules, and takes advantage of the underlying topology in protein interaction networks and the structure of graphs in the Gene Ontology. We apply our method to proteins from the Human Protein Reference Database (HPRD) and show that, in comparison with other approaches, it predicts protein functions with significantly higher recall with no loss of precision. Specifically, it achieves 51% precision and 60% recall versus 45% and 26% for Majority and 24% and 61% for χ²-statistics, respectively. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Giant hub Src and Syk tyrosine kinase thermodynamic profiles recapitulate evolution

    Science.gov (United States)

    Phillips, J. C.

    2017-10-01

    Thermodynamic scaling theory, previously applied mainly to small proteins, here analyzes quantitative evolution of the titled functional network giant hub enzymes. The broad domain structure identified homologically is confirmed hydropathically using amino acid sequences only. The most surprising results concern the evolution of the tyrosine kinase globular surface roughness from avians to mammals, which is first order, compared to the evolution within mammals from rodents to humans, which is second order. The mystery of the unique amide terminal region of proto oncogene tyrosine protein kinase is resolved by the discovery there of a rare hydroneutral septad targeting cluster, which is paralleled by an equally rare octad catalytic cluster in tyrosine kinase in humans and a few other species (cat and dog). These results, which go far towards explaining why these proteins are among the largest giant hubs in protein interaction networks, use no adjustable parameters.

  20. Statistical theory of neutral protein evolution by random site mutations

    Indian Academy of Sciences (India)

    Administrator

    Understanding the features of the protein conformational space represents a key component to characterize ... Neutral evolution; protein design; mutations; foldability criteria. 1. Introduction ... analysis of the vast evolutionary landscape is re- ... intra-molecular interactions in the protein which may not be ... This is the main in-.

  1. A novel Random Walk algorithm with Compulsive Evolution for heat exchanger network synthesis

    International Nuclear Information System (INIS)

    Xiao, Yuan; Cui, Guomin

    2017-01-01

    Highlights: • A novel Random Walk Algorithm with Compulsive Evolution is proposed for HENS. • A simple and feasible evolution strategy is presented in RWCE algorithm. • The integer and continuous variables of HEN are optimized simultaneously in RWCE. • RWCE is demonstrated a relatively strong global search ability in HEN optimization. - Abstract: The heat exchanger network (HEN) synthesis can be characterized as highly combinatorial, nonlinear and nonconvex, contributing to unmanageable computational time and a challenge in identifying the global optimal network design. Stochastic methods are robust and show a powerful global optimizing ability. Based on the common characteristic of different stochastic methods, namely randomness, a novel Random Walk algorithm with Compulsive Evolution (RWCE) is proposed to achieve the best possible total annual cost of heat exchanger network with the relatively simple and feasible evolution strategy. A population of heat exchanger networks is first randomly initialized. Next, the heat load of heat exchanger for each individual is randomly expanded or contracted in order to optimize both the integer and continuous variables simultaneously and to obtain the lowest total annual cost. Besides, when individuals approach to local optima, there is a certain probability for them to compulsively accept the imperfect networks in order to keep the population diversity and ability of global optimization. The presented method is then applied to heat exchanger network synthesis cases from the literature to compare the best results published. RWCE consistently has a lower computed total annual cost compared to previously published results.

  2. Combining neural networks for protein secondary structure prediction

    DEFF Research Database (Denmark)

    Riis, Søren Kamaric

    1995-01-01

    In this paper structured neural networks are applied to the problem of predicting the secondary structure of proteins. A hierarchical approach is used where specialized neural networks are designed for each structural class and then combined using another neural network. The submodels are designed...... by using a priori knowledge of the mapping between protein building blocks and the secondary structure and by using weight sharing. Since none of the individual networks have more than 600 adjustable weights over-fitting is avoided. When ensembles of specialized experts are combined the performance...

  3. Neural Networks for protein Structure Prediction

    DEFF Research Database (Denmark)

    Bohr, Henrik

    1998-01-01

    This is a review about neural network applications in bioinformatics. Especially the applications to protein structure prediction, e.g. prediction of secondary structures, prediction of surface structure, fold class recognition and prediction of the 3-dimensional structure of protein backbones...

  4. An Overview on Wireless Sensor Networks Technology and Evolution

    Directory of Open Access Journals (Sweden)

    Chiara Buratti

    2009-08-01

    Full Text Available Wireless sensor networks (WSNs enable new applications and require non-conventional paradigms for protocol design due to several constraints. Owing to the requirement for low device complexity together with low energy consumption (i.e., long network lifetime, a proper balance between communication and signal/data processing capabilities must be found. This motivates a huge effort in research activities, standardization process, and industrial investments on this field since the last decade. This survey paper aims at reporting an overview of WSNs technologies, main applications and standards, features in WSNs design, and evolutions. In particular, some peculiar applications, such as those based on environmental monitoring, are discussed and design strategies highlighted; a case study based on a real implementation is also reported. Trends and possible evolutions are traced. Emphasis is given to the IEEE 802.15.4 technology, which enables many applications of WSNs. Some example of performance characteristics of 802.15.4-based networks are shown and discussed as a function of the size of the WSN and the data type to be exchanged among nodes.

  5. Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks.

    Science.gov (United States)

    Lin, Wen-Hsien; Liu, Wei-Chung; Hwang, Ming-Jing

    2009-03-11

    Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure. Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined. Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene

  6. Complexities’ day-to-day dynamic evolution analysis and prediction for a Didi taxi trip network based on complex network theory

    Science.gov (United States)

    Zhang, Lin; Lu, Jian; Zhou, Jialin; Zhu, Jinqing; Li, Yunxuan; Wan, Qian

    2018-03-01

    Didi Dache is the most popular taxi order mobile app in China, which provides online taxi-hailing service. The obtained big database from this app could be used to analyze the complexities’ day-to-day dynamic evolution of Didi taxi trip network (DTTN) from the level of complex network dynamics. First, this paper proposes the data cleaning and modeling methods for expressing Nanjing’s DTTN as a complex network. Second, the three consecutive weeks’ data are cleaned to establish 21 DTTNs based on the proposed big data processing technology. Then, multiple topology measures that characterize the complexities’ day-to-day dynamic evolution of these networks are provided. Third, these measures of 21 DTTNs are calculated and subsequently explained with actual implications. They are used as a training set for modeling the BP neural network which is designed for predicting DTTN complexities evolution. Finally, the reliability of the designed BP neural network is verified by comparing with the actual data and the results obtained from ARIMA method simultaneously. Because network complexities are the basis for modeling cascading failures and conducting link prediction in complex system, this proposed research framework not only provides a novel perspective for analyzing DTTN from the level of system aggregated behavior, but can also be used to improve the DTTN management level.

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

    Science.gov (United States)

    Barber, Alan E; Babbitt, Patricia C

    2012-11-01

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

  8. Unified model for vortex-string network evolution

    International Nuclear Information System (INIS)

    Martins, C.J.A.P.; Moore, J.N.; Shellard, E.P.S.

    2004-01-01

    We describe and numerically test the velocity-dependent one-scale string evolution model, a simple analytic approach describing a string network with the averaged correlation length and velocity. We show that it accurately reproduces the large-scale behavior (in particular the scaling laws) of numerical simulations of both Goto-Nambu and field theory string networks. We explicitly demonstrate the relation between the high-energy physics approach and the damped and nonrelativistic limits which are relevant for condensed matter physics. We also reproduce experimental results in this context and show that the vortex-string density is significantly reduced by loop production, an effect not included in the usual 'coarse-grained' approach

  9. A Topology Evolution Model Based on Revised PageRank Algorithm and Node Importance for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Xiaogang Qi

    2015-01-01

    Full Text Available Wireless sensor network (WSN is a classical self-organizing communication network, and its topology evolution currently becomes one of the attractive issues in this research field. Accordingly, the problem is divided into two subproblems: one is to design a new preferential attachment method and the other is to analyze the dynamics of the network topology evolution. To solve the first subproblem, a revised PageRank algorithm, called Con-rank, is proposed to evaluate the node importance upon the existing node contraction, and then a novel preferential attachment is designed based on the node importance calculated by the proposed Con-rank algorithm. To solve the second one, we firstly analyze the network topology evolution dynamics in a theoretical way and then simulate the evolution process. Theoretical analysis proves that the network topology evolution of our model agrees with power-law distribution, and simulation results are well consistent with our conclusions obtained from the theoretical analysis and simultaneously show that our topology evolution model is superior to the classic BA model in the average path length and the clustering coefficient, and the network topology is more robust and can tolerate the random attacks.

  10. Design principles for cancer therapy guided by changes in complexity of protein-protein interaction networks.

    Science.gov (United States)

    Benzekry, Sebastian; Tuszynski, Jack A; Rietman, Edward A; Lakka Klement, Giannoula

    2015-05-28

    The ever-increasing expanse of online bioinformatics data is enabling new ways to, not only explore the visualization of these data, but also to apply novel mathematical methods to extract meaningful information for clinically relevant analysis of pathways and treatment decisions. One of the methods used for computing topological characteristics of a space at different spatial resolutions is persistent homology. This concept can also be applied to network theory, and more specifically to protein-protein interaction networks, where the number of rings in an individual cancer network represents a measure of complexity. We observed a linear correlation of R = -0.55 between persistent homology and 5-year survival of patients with a variety of cancers. This relationship was used to predict the proteins within a protein-protein interaction network with the most impact on cancer progression. By re-computing the persistent homology after computationally removing an individual node (protein) from the protein-protein interaction network, we were able to evaluate whether such an inhibition would lead to improvement in patient survival. The power of this approach lied in its ability to identify the effects of inhibition of multiple proteins and in the ability to expose whether the effect of a single inhibition may be amplified by inhibition of other proteins. More importantly, we illustrate specific examples of persistent homology calculations, which correctly predict the survival benefit observed effects in clinical trials using inhibitors of the identified molecular target. We propose that computational approaches such as persistent homology may be used in the future for selection of molecular therapies in clinic. The technique uses a mathematical algorithm to evaluate the node (protein) whose inhibition has the highest potential to reduce network complexity. The greater the drop in persistent homology, the greater reduction in network complexity, and thus a larger

  11. On the role of sparseness in the evolution of modularity in gene regulatory networks.

    Science.gov (United States)

    Espinosa-Soto, Carlos

    2018-05-01

    Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

  12. Network homophily and the evolution of the pay-it-forward reciprocity.

    Directory of Open Access Journals (Sweden)

    Yen-Sheng Chiang

    Full Text Available The pay-it-forward reciprocity is a type of cooperative behavior that people who have benefited from others return favors to third parties other than the benefactors, thus pushing forward a cascade of kindness. The phenomenon of the pay-it-forward reciprocity is ubiquitous, yet how it evolves to be part of human sociality has not been fully understood. We develop an evolutionary dynamics model to investigate how network homophily influences the evolution of the pay-it-forward reciprocity. Manipulating the extent to which actors carrying the same behavioral trait are linked in networks, the computer simulation model shows that strong network homophily helps consolidate the adaptive advantage of cooperation, yet introducing some heterophily to the formation of network helps advance cooperation's scale further. Our model enriches the literature of inclusive fitness theory by demonstrating the conditions under which cooperation or reciprocity can be selected for in evolution when social interaction is not confined exclusively to relatives.

  13. Network homophily and the evolution of the pay-it-forward reciprocity.

    Science.gov (United States)

    Chiang, Yen-Sheng; Takahashi, Nobuyuki

    2011-01-01

    The pay-it-forward reciprocity is a type of cooperative behavior that people who have benefited from others return favors to third parties other than the benefactors, thus pushing forward a cascade of kindness. The phenomenon of the pay-it-forward reciprocity is ubiquitous, yet how it evolves to be part of human sociality has not been fully understood. We develop an evolutionary dynamics model to investigate how network homophily influences the evolution of the pay-it-forward reciprocity. Manipulating the extent to which actors carrying the same behavioral trait are linked in networks, the computer simulation model shows that strong network homophily helps consolidate the adaptive advantage of cooperation, yet introducing some heterophily to the formation of network helps advance cooperation's scale further. Our model enriches the literature of inclusive fitness theory by demonstrating the conditions under which cooperation or reciprocity can be selected for in evolution when social interaction is not confined exclusively to relatives.

  14. Rapid Sampling of Hydrogen Bond Networks for Computational Protein Design.

    Science.gov (United States)

    Maguire, Jack B; Boyken, Scott E; Baker, David; Kuhlman, Brian

    2018-05-08

    Hydrogen bond networks play a critical role in determining the stability and specificity of biomolecular complexes, and the ability to design such networks is important for engineering novel structures, interactions, and enzymes. One key feature of hydrogen bond networks that makes them difficult to rationally engineer is that they are highly cooperative and are not energetically favorable until the hydrogen bonding potential has been satisfied for all buried polar groups in the network. Existing computational methods for protein design are ill-equipped for creating these highly cooperative networks because they rely on energy functions and sampling strategies that are focused on pairwise interactions. To enable the design of complex hydrogen bond networks, we have developed a new sampling protocol in the molecular modeling program Rosetta that explicitly searches for sets of amino acid mutations that can form self-contained hydrogen bond networks. For a given set of designable residues, the protocol often identifies many alternative sets of mutations/networks, and we show that it can readily be applied to large sets of residues at protein-protein interfaces or in the interior of proteins. The protocol builds on a recently developed method in Rosetta for designing hydrogen bond networks that has been experimentally validated for small symmetric systems but was not extensible to many larger protein structures and complexes. The sampling protocol we describe here not only recapitulates previously validated designs with performance improvements but also yields viable hydrogen bond networks for cases where the previous method fails, such as the design of large, asymmetric interfaces relevant to engineering protein-based therapeutics.

  15. Stoichiometric balance of protein copy numbers is measurable and functionally significant in a protein-protein interaction network for yeast endocytosis.

    Science.gov (United States)

    Holland, David O; Johnson, Margaret E

    2018-03-01

    Stoichiometric balance, or dosage balance, implies that proteins that are subunits of obligate complexes (e.g. the ribosome) should have copy numbers expressed to match their stoichiometry in that complex. Establishing balance (or imbalance) is an important tool for inferring subunit function and assembly bottlenecks. We show here that these correlations in protein copy numbers can extend beyond complex subunits to larger protein-protein interactions networks (PPIN) involving a range of reversible binding interactions. We develop a simple method for quantifying balance in any interface-resolved PPINs based on network structure and experimentally observed protein copy numbers. By analyzing such a network for the clathrin-mediated endocytosis (CME) system in yeast, we found that the real protein copy numbers were significantly more balanced in relation to their binding partners compared to randomly sampled sets of yeast copy numbers. The observed balance is not perfect, highlighting both under and overexpressed proteins. We evaluate the potential cost and benefits of imbalance using two criteria. First, a potential cost to imbalance is that 'leftover' proteins without remaining functional partners are free to misinteract. We systematically quantify how this misinteraction cost is most dangerous for strong-binding protein interactions and for network topologies observed in biological PPINs. Second, a more direct consequence of imbalance is that the formation of specific functional complexes depends on relative copy numbers. We therefore construct simple kinetic models of two sub-networks in the CME network to assess multi-protein assembly of the ARP2/3 complex and a minimal, nine-protein clathrin-coated vesicle forming module. We find that the observed, imperfectly balanced copy numbers are less effective than balanced copy numbers in producing fast and complete multi-protein assemblies. However, we speculate that strategic imbalance in the vesicle forming module

  16. New Measurement for Correlation of Co-evolution Relationship of Subsequences in Protein.

    Science.gov (United States)

    Gao, Hongyun; Yu, Xiaoqing; Dou, Yongchao; Wang, Jun

    2015-12-01

    Many computational tools have been developed to measure the protein residues co-evolution. Most of them only focus on co-evolution for pairwise residues in a protein sequence. However, number of residues participate in co-evolution might be multiple. And some co-evolved residues are clustered in several distinct regions in primary structure. Therefore, the co-evolution among the adjacent residues and the correlation between the distinct regions offer insights into function and evolution of the protein and residues. Subsequence is used to represent the adjacent multiple residues in one distinct region. In the paper, co-evolution relationship in each subsequence is represented by mutual information matrix (MIM). Then, Pearson's correlation coefficient: R value is developed to measure the similarity correlation of two MIMs. MSAs from Catalytic Data Base (Catalytic Site Atlas, CSA) are used for testing. R value characterizes a specific class of residues. In contrast to individual pairwise co-evolved residues, adjacent residues without high individual MI values are found since the co-evolved relationship among them is similar to that among another set of adjacent residues. These subsequences possess some flexibility in the composition of side chains, such as the catalyzed environment.

  17. Evolution of Positioning Techniques in Cellular Networks, from 2G to 4G

    Directory of Open Access Journals (Sweden)

    Rafael Saraiva Campos

    2017-01-01

    Full Text Available This review paper presents within a common framework the mobile station positioning methods applied in 2G, 3G, and 4G cellular networks, as well as the structure of the related 3GPP technical specifications. The evolution path through the generations is explored in three steps at each level: first, the new network elements supporting localization features are introduced; then, the standard localization methods are described; finally, the protocols providing specific support to mobile station positioning are studied. To allow a better understanding, this paper also brings a brief review of the cellular networks evolution paths.

  18. CNNcon: improved protein contact maps prediction using cascaded neural networks.

    Directory of Open Access Journals (Sweden)

    Wang Ding

    Full Text Available BACKGROUNDS: Despite continuing progress in X-ray crystallography and high-field NMR spectroscopy for determination of three-dimensional protein structures, the number of unsolved and newly discovered sequences grows much faster than that of determined structures. Protein modeling methods can possibly bridge this huge sequence-structure gap with the development of computational science. A grand challenging problem is to predict three-dimensional protein structure from its primary structure (residues sequence alone. However, predicting residue contact maps is a crucial and promising intermediate step towards final three-dimensional structure prediction. Better predictions of local and non-local contacts between residues can transform protein sequence alignment to structure alignment, which can finally improve template based three-dimensional protein structure predictors greatly. METHODS: CNNcon, an improved multiple neural networks based contact map predictor using six sub-networks and one final cascade-network, was developed in this paper. Both the sub-networks and the final cascade-network were trained and tested with their corresponding data sets. While for testing, the target protein was first coded and then input to its corresponding sub-networks for prediction. After that, the intermediate results were input to the cascade-network to finish the final prediction. RESULTS: The CNNcon can accurately predict 58.86% in average of contacts at a distance cutoff of 8 Å for proteins with lengths ranging from 51 to 450. The comparison results show that the present method performs better than the compared state-of-the-art predictors. Particularly, the prediction accuracy keeps steady with the increase of protein sequence length. It indicates that the CNNcon overcomes the thin density problem, with which other current predictors have trouble. This advantage makes the method valuable to the prediction of long length proteins. As a result, the effective

  19. The Population Genomics of Sunflowers and Genomic Determinants of Protein Evolution Revealed by RNAseq

    Directory of Open Access Journals (Sweden)

    Loren H. Rieseberg

    2012-10-01

    Full Text Available Few studies have investigated the causes of evolutionary rate variation among plant nuclear genes, especially in recently diverged species still capable of hybridizing in the wild. The recent advent of Next Generation Sequencing (NGS permits investigation of genome wide rates of protein evolution and the role of selection in generating and maintaining divergence. Here, we use individual whole-transcriptome sequencing (RNAseq to refine our understanding of the population genomics of wild species of sunflowers (Helianthus spp. and the factors that affect rates of protein evolution. We aligned 35 GB of transcriptome sequencing data and identified 433,257 polymorphic sites (SNPs in a reference transcriptome comprising 16,312 genes. Using SNP markers, we identified strong population clustering largely corresponding to the three species analyzed here (Helianthus annuus, H. petiolaris, H. debilis, with one distinct early generation hybrid. Then, we calculated the proportions of adaptive substitution fixed by selection (alpha and identified gene ontology categories with elevated values of alpha. The “response to biotic stimulus” category had the highest mean alpha across the three interspecific comparisons, implying that natural selection imposed by other organisms plays an important role in driving protein evolution in wild sunflowers. Finally, we examined the relationship between protein evolution (dN/dS ratio and several genomic factors predicted to co-vary with protein evolution (gene expression level, divergence and specificity, genetic divergence [FST], and nucleotide diversity pi. We find that variation in rates of protein divergence was correlated with gene expression level and specificity, consistent with results from a broad range of taxa and timescales. This would in turn imply that these factors govern protein evolution both at a microevolutionary and macroevolutionary timescale. Our results contribute to a general understanding of the

  20. Predicting and validating protein interactions using network structure.

    Directory of Open Access Journals (Sweden)

    Pao-Yang Chen

    2008-07-01

    Full Text Available Protein interactions play a vital part in the function of a cell. As experimental techniques for detection and validation of protein interactions are time consuming, there is a need for computational methods for this task. Protein interactions appear to form a network with a relatively high degree of local clustering. In this paper we exploit this clustering by suggesting a score based on triplets of observed protein interactions. The score utilises both protein characteristics and network properties. Our score based on triplets is shown to complement existing techniques for predicting protein interactions, outperforming them on data sets which display a high degree of clustering. The predicted interactions score highly against test measures for accuracy. Compared to a similar score derived from pairwise interactions only, the triplet score displays higher sensitivity and specificity. By looking at specific examples, we show how an experimental set of interactions can be enriched and validated. As part of this work we also examine the effect of different prior databases upon the accuracy of prediction and find that the interactions from the same kingdom give better results than from across kingdoms, suggesting that there may be fundamental differences between the networks. These results all emphasize that network structure is important and helps in the accurate prediction of protein interactions. The protein interaction data set and the program used in our analysis, and a list of predictions and validations, are available at http://www.stats.ox.ac.uk/bioinfo/resources/PredictingInteractions.

  1. Using the clustered circular layout as an informative method for visualizing protein-protein interaction networks.

    Science.gov (United States)

    Fung, David C Y; Wilkins, Marc R; Hart, David; Hong, Seok-Hee

    2010-07-01

    The force-directed layout is commonly used in computer-generated visualizations of protein-protein interaction networks. While it is good for providing a visual outline of the protein complexes and their interactions, it has two limitations when used as a visual analysis method. The first is poor reproducibility. Repeated running of the algorithm does not necessarily generate the same layout, therefore, demanding cognitive readaptation on the investigator's part. The second limitation is that it does not explicitly display complementary biological information, e.g. Gene Ontology, other than the protein names or gene symbols. Here, we present an alternative layout called the clustered circular layout. Using the human DNA replication protein-protein interaction network as a case study, we compared the two network layouts for their merits and limitations in supporting visual analysis.

  2. Modeling Evolution on Nearly Neutral Network Fitness Landscapes

    Science.gov (United States)

    Yakushkina, Tatiana; Saakian, David B.

    2017-08-01

    To describe virus evolution, it is necessary to define a fitness landscape. In this article, we consider the microscopic models with the advanced version of neutral network fitness landscapes. In this problem setting, we suppose a fitness difference between one-point mutation neighbors to be small. We construct a modification of the Wright-Fisher model, which is related to ordinary infinite population models with nearly neutral network fitness landscape at the large population limit. From the microscopic models in the realistic sequence space, we derive two versions of nearly neutral network models: with sinks and without sinks. We claim that the suggested model describes the evolutionary dynamics of RNA viruses better than the traditional Wright-Fisher model with few sequences.

  3. Potato leafroll virus structural proteins manipulate overlapping, yet distinct protein interaction networks during infection.

    Science.gov (United States)

    DeBlasio, Stacy L; Johnson, Richard; Sweeney, Michelle M; Karasev, Alexander; Gray, Stewart M; MacCoss, Michael J; Cilia, Michelle

    2015-06-01

    Potato leafroll virus (PLRV) produces a readthrough protein (RTP) via translational readthrough of the coat protein amber stop codon. The RTP functions as a structural component of the virion and as a nonincorporated protein in concert with numerous insect and plant proteins to regulate virus movement/transmission and tissue tropism. Affinity purification coupled to quantitative MS was used to generate protein interaction networks for a PLRV mutant that is unable to produce the read through domain (RTD) and compared to the known wild-type PLRV protein interaction network. By quantifying differences in the protein interaction networks, we identified four distinct classes of PLRV-plant interactions: those plant and nonstructural viral proteins interacting with assembled coat protein (category I); plant proteins in complex with both coat protein and RTD (category II); plant proteins in complex with the RTD (category III); and plant proteins that had higher affinity for virions lacking the RTD (category IV). Proteins identified as interacting with the RTD are potential candidates for regulating viral processes that are mediated by the RTP such as phloem retention and systemic movement and can potentially be useful targets for the development of strategies to prevent infection and/or viral transmission of Luteoviridae species that infect important crop species. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Diversity and evolution of ABC proteins in basidiomycetes.

    Science.gov (United States)

    Kovalchuk, Andriy; Lee, Yong-Hwan; Asiegbu, Fred O

    2013-01-01

    ABC proteins constitute one of the largest families of proteins. They are implicated in wide variety of cellular processes ranging from ribosome biogenesis to multidrug resistance. With the advance of fungal genomics, the number of known fungal ABC proteins increases rapidly but the information on their biological functions remains scarce. In this work we extended the previous analysis of fungal ABC proteins to include recently sequenced species of basidiomycetes. We performed an identification and initial cataloging of ABC proteins from 23 fungal species representing 10 orders within class Agaricomycotina. We identified more than 1000 genes coding for ABC proteins. Comparison of sets of ABC proteins present in basidiomycetes and ascomycetes revealed the existence of two groups of ABC proteins specific for basidiomycetes. Results of survey should contribute to the better understanding of evolution of ABC proteins in fungi and support further experimental work on their characterization.

  5. Trends in global warming and evolution of matrix protein 2 family from influenza A virus.

    Science.gov (United States)

    Yan, Shao-Min; Wu, Guang

    2009-12-01

    The global warming is an important factor affecting the biological evolution, and the influenza is an important disease that threatens humans with possible epidemics or pandemics. In this study, we attempted to analyze the trends in global warming and evolution of matrix protein 2 family from influenza A virus, because this protein is a target of anti-flu drug, and its mutation would have significant effect on the resistance to anti-flu drugs. The evolution of matrix protein 2 of influenza A virus from 1959 to 2008 was defined using the unpredictable portion of amino-acid pair predictability. Then the trend in this evolution was compared with the trend in the global temperature, the temperature in north and south hemispheres, and the temperature in influenza A virus sampling site, and species carrying influenza A virus. The results showed the similar trends in global warming and in evolution of M2 proteins although we could not correlate them at this stage of study. The study suggested the potential impact of global warming on the evolution of proteins from influenza A virus.

  6. Rampant adaptive evolution in regions of proteins with unknown function in Drosophila simulans.

    Directory of Open Access Journals (Sweden)

    Alisha K Holloway

    2007-10-01

    Full Text Available Adaptive protein evolution is pervasive in Drosophila. Genomic studies, thus far, have analyzed each protein as a single entity. However, the targets of adaptive events may be localized to particular parts of proteins, such as protein domains or regions involved in protein folding. We compared the population genetic mechanisms driving sequence polymorphism and divergence in defined protein domains and non-domain regions. Interestingly, we find that non-domain regions of proteins are more frequent targets of directional selection. Protein domains are also evolving under directional selection, but appear to be under stronger purifying selection than non-domain regions. Non-domain regions of proteins clearly play a major role in adaptive protein evolution on a genomic scale and merit future investigations of their functional properties.

  7. Enhancing the Functional Content of Eukaryotic Protein Interaction Networks

    Science.gov (United States)

    Pandey, Gaurav; Arora, Sonali; Manocha, Sahil; Whalen, Sean

    2014-01-01

    Protein interaction networks are a promising type of data for studying complex biological systems. However, despite the rich information embedded in these networks, these networks face important data quality challenges of noise and incompleteness that adversely affect the results obtained from their analysis. Here, we apply a robust measure of local network structure called common neighborhood similarity (CNS) to address these challenges. Although several CNS measures have been proposed in the literature, an understanding of their relative efficacies for the analysis of interaction networks has been lacking. We follow the framework of graph transformation to convert the given interaction network into a transformed network corresponding to a variety of CNS measures evaluated. The effectiveness of each measure is then estimated by comparing the quality of protein function predictions obtained from its corresponding transformed network with those from the original network. Using a large set of human and fly protein interactions, and a set of over GO terms for both, we find that several of the transformed networks produce more accurate predictions than those obtained from the original network. In particular, the measure and other continuous CNS measures perform well this task, especially for large networks. Further investigation reveals that the two major factors contributing to this improvement are the abilities of CNS measures to prune out noisy edges and enhance functional coherence in the transformed networks. PMID:25275489

  8. US long distance fiber optic networks: Technology, evolution and advanced concepts. Volume 2: Fiber optic technology and long distance networks

    Science.gov (United States)

    1986-10-01

    The study projects until 2000 the evolution of long distance fiber optic networks in the U.S. Volume 1 is the Executive Summary. Volume 2 focuses on fiber optic components and systems that are directly related to the operation of long-haul networks. Optimistic, pessimistic and most likely scenarios of technology development are presented. The activities of national and regional companies implementing fiber long haul networks are also highlighted, along with an analysis of the market and regulatory forces affecting network evolution. Volume 3 presents advanced fiber optic network concept definitions. Inter-LATA traffic is quantified and forms the basis for the construction of 11-, 15-, 17-, and 23-node networks. Using the technology projections from Volume 2, a financial model identifies cost drivers and determines circuit mile costs between any two LATAs. A comparison of fiber optics with alternative transmission concludes the report.

  9. Protein complex prediction based on k-connected subgraphs in protein interaction network

    OpenAIRE

    Habibi, Mahnaz; Eslahchi, Changiz; Wong, Limsoon

    2010-01-01

    Abstract Background Protein complexes play an important role in cellular mechanisms. Recently, several methods have been presented to predict protein complexes in a protein interaction network. In these methods, a protein complex is predicted as a dense subgraph of protein interactions. However, interactions data are incomplete and a protein complex does not have to be a complete or dense subgraph. Results We propose a more appropriate protein complex prediction method, CFA, that is based on ...

  10. The genesis and evolution of the African Field Epidemiology Network

    African Journals Online (AJOL)

    The genesis and evolution of the African Field Epidemiology Network. David Mukanga, Mufuta Tshimanga, Frederick Wurapa, David Serwada, George Pariyo, Fred Wabwire-Mangen, Sheba Gitta, Stella Chungong, Murray Trostle, Peter Nsubuga ...

  11. Chaotic evolution of prisoner's dilemma game with volunteering on interdependent networks

    Science.gov (United States)

    Luo, Chao; Zhang, Xiaolin; Zheng, YuanJie

    2017-06-01

    In this article, the evolution of prisoner's dilemma game with volunteering on interdependent networks is investigated. Different from the traditional two-strategy game, voluntary participation as an additional strategy is involved in repeated game, that can introduce more complex evolutionary dynamics. And, interdependent networks provide a more generalized network architecture to study the intricate variability of dynamics. We have showed that voluntary participation could effectively promote the density of co-operation, that is also greatly affected by interdependent strength between two coupled networks. We further discussed the influence of interdependent strength on the densities of different strategies and found that an intermediate interdependence would play a bigger role on the evolution of dynamics. Subsequently, the critical values of the defection temptation for phase transitions under different conditions have been studied. Moreover, the global oscillations induced by the circle of dominance of three strategies on interdependent networks have been quantitatively investigated. Counter-intuitively, the oscillations of strategy densities are not periodic or stochastic, but have rich dynamical behaviors. By means of various analysis tools, we have demonstrated the global oscillations of strategy densities possessed chaotic characteristics.

  12. Data management of protein interaction networks

    CERN Document Server

    Cannataro, Mario

    2012-01-01

    Interactomics: a complete survey from data generation to knowledge extraction With the increasing use of high-throughput experimental assays, more and more protein interaction databases are becoming available. As a result, computational analysis of protein-to-protein interaction (PPI) data and networks, now known as interactomics, has become an essential tool to determine functionally associated proteins. From wet lab technologies to data management to knowledge extraction, this timely book guides readers through the new science of interactomics, giving them the tools needed to: Generate

  13. Semigroup methods for evolution equations on networks

    CERN Document Server

    Mugnolo, Delio

    2014-01-01

    This concise text is based on a series of lectures held only a few years ago and originally intended as an introduction to known results on linear hyperbolic and parabolic equations.  Yet the topic of differential equations on graphs, ramified spaces, and more general network-like objects has recently gained significant momentum and, well beyond the confines of mathematics, there is a lively interdisciplinary discourse on all aspects of so-called complex networks. Such network-like structures can be found in virtually all branches of science, engineering and the humanities, and future research thus calls for solid theoretical foundations.      This book is specifically devoted to the study of evolution equations – i.e., of time-dependent differential equations such as the heat equation, the wave equation, or the Schrödinger equation (quantum graphs) – bearing in mind that the majority of the literature in the last ten years on the subject of differential equations of graphs has been devoted to ellip...

  14. Self-organized Criticality in a Modified Evolution Model on Generalized Barabasi-Albert Scale-Free Networks

    International Nuclear Information System (INIS)

    Lin Min; Wang Gang; Chen Tianlun

    2007-01-01

    A modified evolution model of self-organized criticality on generalized Barabasi-Albert (GBA) scale-free networks is investigated. In our model, we find that spatial and temporal correlations exhibit critical behaviors. More importantly, these critical behaviors change with the parameter b, which weights the distance in comparison with the degree in the GBA network evolution.

  15. Limited Influence of Oxygen on the Evolution of Chemical Diversity in Metabolic Networks

    Directory of Open Access Journals (Sweden)

    Kazuhiro Takemoto

    2013-10-01

    Full Text Available Oxygen is thought to promote species and biomolecule diversity. Previous studies have suggested that oxygen expands metabolic networks by acquiring metabolites with different chemical properties (higher hydrophobicity, for example. However, such conclusions are typically based on biased evaluation, and are therefore non-conclusive. Thus, we re-investigated the effect of oxygen on metabolic evolution using a phylogenetic comparative method and metadata analysis to reduce the bias as much as possible. Notably, we found no difference in metabolic network expansion between aerobes and anaerobes when evaluating phylogenetic relationships. Furthermore, we showed that previous studies have overestimated or underestimated the degrees of differences in the chemical properties (e.g., hydrophobicity between oxic and anoxic metabolites in metabolic networks of unicellular organisms; however, such overestimation was not observed when considering the metabolic networks of multicellular organisms. These findings indicate that the contribution of oxygen to increased chemical diversity in metabolic networks is lower than previously thought; rather, phylogenetic signals and cell-cell communication result in increased chemical diversity. However, this conclusion does not contradict the effect of oxygen on metabolic evolution; instead, it provides a deeper understanding of how oxygen contributes to metabolic evolution despite several limitations in data analysis methods.

  16. Evolution of the Quorum network and the mobilome (plasmids and bacteriophages) in clinical strains of Acinetobacter baumannii during a decade.

    Science.gov (United States)

    López, M; Rueda, A; Florido, J P; Blasco, L; Fernández-García, L; Trastoy, R; Fernández-Cuenca, F; Martínez-Martínez, L; Vila, J; Pascual, A; Bou, G; Tomas, M

    2018-02-06

    In this study, we compared eighteen clinical strains of A. baumannii belonging to the ST-2 clone and isolated from patients in the same intensive care unit (ICU) in 2000 (9 strains referred to collectively as Ab_GEIH-2000) and 2010 (9 strains referred to collectively as Ab_GEIH-2010), during the GEIH-REIPI project (Umbrella BioProject PRJNA422585). We observed two main molecular differences between the Ab_GEIH-2010 and the Ab_GEIH-2000 collections, acquired over the course of the decade long sampling interval and involving the mobilome: i) a plasmid harbouring genes for bla OXA 24/40 ß-lactamase and abKA/abkB proteins of a toxin-antitoxin system; and ii) two temperate bacteriophages, Ab105-1ϕ (63 proteins) and Ab105-2ϕ (93 proteins), containing important viral defence proteins. Moreover, all Ab_GEIH-2010 strains contained a Quorum functional network of Quorum Sensing (QS) and Quorum Quenching (QQ) mechanisms, including a new QQ enzyme, AidA, which acts as a bacterial defence mechanism against the exogenous 3-oxo-C12-HSL. Interestingly, the infective capacity of the bacteriophages isolated in this study (Ab105-1ϕ and Ab105-2ϕ) was higher in the Ab_GEIH-2010 strains (carrying a functional Quorum network) than in the Ab_GEIH-2000 strains (carrying a deficient Quorum network), in which the bacteriophages showed little or no infectivity. This is the first study about the evolution of the Quorum network and the mobilome in clinical strains of Acinetobacter baumannii during a decade.

  17. Discovering functional interdependence relationship in PPI networks for protein complex identification.

    Science.gov (United States)

    Lam, Winnie W M; Chan, Keith C C

    2012-04-01

    Protein molecules interact with each other in protein complexes to perform many vital functions, and different computational techniques have been developed to identify protein complexes in protein-protein interaction (PPI) networks. These techniques are developed to search for subgraphs of high connectivity in PPI networks under the assumption that the proteins in a protein complex are highly interconnected. While these techniques have been shown to be quite effective, it is also possible that the matching rate between the protein complexes they discover and those that are previously determined experimentally be relatively low and the "false-alarm" rate can be relatively high. This is especially the case when the assumption of proteins in protein complexes being more highly interconnected be relatively invalid. To increase the matching rate and reduce the false-alarm rate, we have developed a technique that can work effectively without having to make this assumption. The name of the technique called protein complex identification by discovering functional interdependence (PCIFI) searches for protein complexes in PPI networks by taking into consideration both the functional interdependence relationship between protein molecules and the network topology of the network. The PCIFI works in several steps. The first step is to construct a multiple-function protein network graph by labeling each vertex with one or more of the molecular functions it performs. The second step is to filter out protein interactions between protein pairs that are not functionally interdependent of each other in the statistical sense. The third step is to make use of an information-theoretic measure to determine the strength of the functional interdependence between all remaining interacting protein pairs. Finally, the last step is to try to form protein complexes based on the measure of the strength of functional interdependence and the connectivity between proteins. For performance evaluation

  18. Network based approaches reveal clustering in protein point patterns

    Science.gov (United States)

    Parker, Joshua; Barr, Valarie; Aldridge, Joshua; Samelson, Lawrence E.; Losert, Wolfgang

    2014-03-01

    Recent advances in super-resolution imaging have allowed for the sub-diffraction measurement of the spatial location of proteins on the surfaces of T-cells. The challenge is to connect these complex point patterns to the internal processes and interactions, both protein-protein and protein-membrane. We begin analyzing these patterns by forming a geometric network amongst the proteins and looking at network measures, such the degree distribution. This allows us to compare experimentally observed patterns to models. Specifically, we find that the experimental patterns differ from heterogeneous Poisson processes, highlighting an internal clustering structure. Further work will be to compare our results to simulated protein-protein interactions to determine clustering mechanisms.

  19. Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.

    Science.gov (United States)

    Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

    2017-07-25

    Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

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

    OpenAIRE

    Babbitt, Patricia; Barber, AE; Babbitt, PC

    2012-01-01

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

  1. Protein change in plant evolution: tracing one thread connecting molecular and phenotypic diversity

    Directory of Open Access Journals (Sweden)

    Madelaine eBartlett

    2013-10-01

    Full Text Available Proteins change over the course of evolutionary time. New protein-coding genes and gene families emerge and diversify, ultimately affecting an organism’s phenotype and interactions with its environment. Here we survey the range of structural protein change observed in plants and review the role these changes have had in the evolution of plant form and function. Verified examples tying evolutionary change in protein structure to phenotypic change remain scarce. We will review the existing examples, as well as draw from investigations into domestication, and quantitative trait locus (QTL cloning studies searching for the molecular underpinnings of natural variation. The evolutionary significance of many cloned QTL has not been assessed, but all the examples identified so far have begun to reveal the extent of protein structural diversity tolerated in natural systems. This molecular (and phenotypic diversity could come to represent part of natural selection’s source material in the adaptive evolution of novel traits. Protein structure and function can change in many distinct ways, but the changes we identified in studies of natural diversity and protein evolution were predicted to fall primarily into one of six categories: altered active and binding sites; hypomorphic and hypermorphic alleles; altered protein-protein interactions; altered domain content; altered protein stability; and altered activity as an activator or repressor. Variability was also observed in the evolutionary scale at which particular changes were observed. Some changes were detected at both micro- and macroevolutionary timescales, while others were observed primarily at deep or shallow phylogenetic levels. This variation might be used to determine the trajectory of future investigations in structural molecular evolution.

  2. Exploration of the dynamic properties of protein complexes predicted from spatially constrained protein-protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Eric A Yen

    2014-05-01

    Full Text Available Protein complexes are not static, but rather highly dynamic with subunits that undergo 1-dimensional diffusion with respect to each other. Interactions within protein complexes are modulated through regulatory inputs that alter interactions and introduce new components and deplete existing components through exchange. While it is clear that the structure and function of any given protein complex is coupled to its dynamical properties, it remains a challenge to predict the possible conformations that complexes can adopt. Protein-fragment Complementation Assays detect physical interactions between protein pairs constrained to ≤8 nm from each other in living cells. This method has been used to build networks composed of 1000s of pair-wise interactions. Significantly, these networks contain a wealth of dynamic information, as the assay is fully reversible and the proteins are expressed in their natural context. In this study, we describe a method that extracts this valuable information in the form of predicted conformations, allowing the user to explore the conformational landscape, to search for structures that correlate with an activity state, and estimate the abundance of conformations in the living cell. The generator is based on a Markov Chain Monte Carlo simulation that uses the interaction dataset as input and is constrained by the physical resolution of the assay. We applied this method to an 18-member protein complex composed of the seven core proteins of the budding yeast Arp2/3 complex and 11 associated regulators and effector proteins. We generated 20,480 output structures and identified conformational states using principle component analysis. We interrogated the conformation landscape and found evidence of symmetry breaking, a mixture of likely active and inactive conformational states and dynamic exchange of the core protein Arc15 between core and regulatory components. Our method provides a novel tool for prediction and

  3. Social roles and the evolution of networks in extreme and isolated environments

    Science.gov (United States)

    Johnson, Jeffrey C.; Boster, James S.; Palinkas, Lawrence A.

    2003-01-01

    This article reports on the evolution of network structure as it relates to formal and informal social roles in well-bounded, isolated groups. Research was conducted at the Amundsen-Scott South Pole Station. Data were collected on crewmembers' networks of social interaction over each of three winter-over periods, when the station is completely isolated. In addition, data were collected on the informal roles played by crewmembers (e.g., instrumental leadership, expressive leadership). The study found that globally coherent networks in winter-over groups were associated with group consensus on the presence of critically important informal social roles (e.g., expressive leadership) where global coherence is the extent to which a network forms a single group composed of a unitary core and periphery as opposed to being factionalized into two or more subgroups. Conversely, the evolution of multiple subgroups was associated with the absence of consensus on critical informal social roles, above all the critically important role of instrumental leader.

  4. Networks in Cell Biology

    Science.gov (United States)

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

    2010-05-01

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

  5. Unveiling network-based functional features through integration of gene expression into protein networks.

    Science.gov (United States)

    Jalili, Mahdi; Gebhardt, Tom; Wolkenhauer, Olaf; Salehzadeh-Yazdi, Ali

    2018-06-01

    Decoding health and disease phenotypes is one of the fundamental objectives in biomedicine. Whereas high-throughput omics approaches are available, it is evident that any single omics approach might not be adequate to capture the complexity of phenotypes. Therefore, integrated multi-omics approaches have been used to unravel genotype-phenotype relationships such as global regulatory mechanisms and complex metabolic networks in different eukaryotic organisms. Some of the progress and challenges associated with integrated omics studies have been reviewed previously in comprehensive studies. In this work, we highlight and review the progress, challenges and advantages associated with emerging approaches, integrating gene expression and protein-protein interaction networks to unravel network-based functional features. This includes identifying disease related genes, gene prioritization, clustering protein interactions, developing the modules, extract active subnetworks and static protein complexes or dynamic/temporal protein complexes. We also discuss how these approaches contribute to our understanding of the biology of complex traits and diseases. This article is part of a Special Issue entitled: Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. A tensegrity model for hydrogen bond networks in proteins

    OpenAIRE

    Bywater, Robert P.

    2017-01-01

    Hydrogen-bonding networks in proteins considered as structural tensile elements are in balance separately from any other stabilising interactions that may be in operation. The hydrogen bond arrangement in the network is reminiscent of tensegrity structures in architecture and sculpture. Tensegrity has been discussed before in cells and tissues and in proteins. In contrast to previous work only hydrogen bonds are studied here. The other interactions within proteins are either much stronger − c...

  7. Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently

    Science.gov (United States)

    Currin, Andrew; Swainston, Neil; Day, Philip J.

    2015-01-01

    The amino acid sequence of a protein affects both its structure and its function. Thus, the ability to modify the sequence, and hence the structure and activity, of individual proteins in a systematic way, opens up many opportunities, both scientifically and (as we focus on here) for exploitation in biocatalysis. Modern methods of synthetic biology, whereby increasingly large sequences of DNA can be synthesised de novo, allow an unprecedented ability to engineer proteins with novel functions. However, the number of possible proteins is far too large to test individually, so we need means for navigating the ‘search space’ of possible protein sequences efficiently and reliably in order to find desirable activities and other properties. Enzymologists distinguish binding (K d) and catalytic (k cat) steps. In a similar way, judicious strategies have blended design (for binding, specificity and active site modelling) with the more empirical methods of classical directed evolution (DE) for improving k cat (where natural evolution rarely seeks the highest values), especially with regard to residues distant from the active site and where the functional linkages underpinning enzyme dynamics are both unknown and hard to predict. Epistasis (where the ‘best’ amino acid at one site depends on that or those at others) is a notable feature of directed evolution. The aim of this review is to highlight some of the approaches that are being developed to allow us to use directed evolution to improve enzyme properties, often dramatically. We note that directed evolution differs in a number of ways from natural evolution, including in particular the available mechanisms and the likely selection pressures. Thus, we stress the opportunities afforded by techniques that enable one to map sequence to (structure and) activity in silico, as an effective means of modelling and exploring protein landscapes. Because known landscapes may be assessed and reasoned about as a whole

  8. Prioritizing disease candidate proteins in cardiomyopathy-specific protein-protein interaction networks based on "guilt by association" analysis.

    Directory of Open Access Journals (Sweden)

    Wan Li

    Full Text Available The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial. Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on "guilt by association" analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on "guilt by association" analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.

  9. Similar Pathogen Targets in Arabidopsis thaliana and Homo sapiens Protein Networks

    Science.gov (United States)

    2012-09-21

    Similar Pathogen Targets in Arabidopsis thaliana and Homo sapiens Protein Networks Paulo Shakarian1*, J. Kenneth Wickiser2 1 Paulo Shakarian...significantly attacked. Citation: Shakarian P, Wickiser JK (2012) Similar Pathogen Targets in Arabidopsis thaliana and Homo sapiens Protein Networks...to 00-00-2012 4. TITLE AND SUBTITLE Similar Pathogen Targets in Arabidopsis thaliana and Homo sapiens Protein Networks 5a. CONTRACT NUMBER 5b

  10. Construction and analysis of protein-protein interaction network correlated with ankylosing spondylitis.

    Science.gov (United States)

    Kanwal, Attiya; Fazal, Sahar

    2018-01-05

    Ankylosing spondylitis, a systemic illness is a foundation of progressing joint swelling that for the most part influences the spine. However, it frequently causes aggravation in different joints far from the spine, and in addition organs, for example, the eyes, heart, lungs, and kidneys. It's an immune system ailment that may be activated by specific sorts of bacterial or viral diseases that initiate an invulnerable reaction that don't close off after the contamination is recuperated. The particular reason for ankylosing spondylitis is obscure, yet hereditary qualities assume a huge part in this condition. The rising apparatuses of network medicine offer a stage to investigate an unpredictable illness at framework level. In this study, we meant to recognize the key proteins and the biological regulator pathways including in AS and further investigating the molecular connectivity between these pathways by the topological examination of the Protein-protein communication (PPI) system. The extended network including of 93 nodes and have 199 interactions respectively scanned from STRING database and some separated small networks. 24 proteins with high BC at the threshold of 0.01 and 55 proteins with large degree at the threshold of 1 have been identified. CD4 with highest BC and Closeness centrality located in the centre of the network. The backbone network derived from high BC proteins presents a clear and visual overview which shows all important regulatory pathways for AS and the crosstalk between them. The finding of this research suggests that AS variation is orchestrated by an integrated PPI network centered on CD4 out of 93 nodes. Ankylosing spondylitis, a systemic disease is an establishment of advancing joint swelling that generally impacts the spine. Be that as it may, it as often as possible causes disturbance in various joints a long way from the spine, and what's more organs. It's a resistant framework affliction that might be actuated by particular sorts

  11. Evolution of networks for body plan patterning; interplay of modularity, robustness and evolvability.

    Directory of Open Access Journals (Sweden)

    Kirsten H Ten Tusscher

    2011-10-01

    Full Text Available A major goal of evolutionary developmental biology (evo-devo is to understand how multicellular body plans of increasing complexity have evolved, and how the corresponding developmental programs are genetically encoded. It has been repeatedly argued that key to the evolution of increased body plan complexity is the modularity of the underlying developmental gene regulatory networks (GRNs. This modularity is considered essential for network robustness and evolvability. In our opinion, these ideas, appealing as they may sound, have not been sufficiently tested. Here we use computer simulations to study the evolution of GRNs' underlying body plan patterning. We select for body plan segmentation and differentiation, as these are considered to be major innovations in metazoan evolution. To allow modular networks to evolve, we independently select for segmentation and differentiation. We study both the occurrence and relation of robustness, evolvability and modularity of evolved networks. Interestingly, we observed two distinct evolutionary strategies to evolve a segmented, differentiated body plan. In the first strategy, first segments and then differentiation domains evolve (SF strategy. In the second scenario segments and domains evolve simultaneously (SS strategy. We demonstrate that under indirect selection for robustness the SF strategy becomes dominant. In addition, as a byproduct of this larger robustness, the SF strategy is also more evolvable. Finally, using a combined functional and architectural approach, we determine network modularity. We find that while SS networks generate segments and domains in an integrated manner, SF networks use largely independent modules to produce segments and domains. Surprisingly, we find that widely used, purely architectural methods for determining network modularity completely fail to establish this higher modularity of SF networks. Finally, we observe that, as a free side effect of evolving segmentation

  12. Reproductive protein evolution in two cryptic species of marine chordate

    Science.gov (United States)

    2011-01-01

    Background Reproductive character displacement (RCD) is a common and taxonomically widespread pattern. In marine broadcast spawning organisms, behavioral and mechanical isolation are absent and prezygotic barriers between species often operate only during the fertilization process. Such barriers are usually a consequence of differences in the way in which sperm and egg proteins interact, so RCD can be manifest as faster evolution of these proteins between species in sympatry than allopatry. Rapid evolution of these proteins often appears to be a consequence of positive (directional) selection. Here, we identify a set of candidate gamete recognition proteins (GRPs) in the ascidian Ciona intestinalis and showed that these GRPs evolve more rapidly than control proteins (those not involved in gamete recognition). Choosing a subset of these gamete recognition proteins that show evidence of positive selection (CIPRO37.40.1, CIPRO60.5.1, CIPRO100.7.1), we then directly test the RCD hypothesis by comparing divergence (omega) and polymorphism (McDonald-Kreitman, Tajima's D, Fu and Li's D and F, Fay and Wu's H) statistics in sympatric and allopatric populations of two distinct forms of C. intestinalis (Types A and B) between which there are strong post-zygotic barriers. Results Candidate gamete recognition proteins from two lineages of C. intestinalis (Type A and B) are evolving more rapidly than control proteins, consistent with patterns seen in insects and mammals. However, ω (dN/dS) is not significantly different between the sympatric and allopatric populations, and none of the polymorphism statistics show significant differences between sympatric and allopatric populations. Conclusions Enhanced prezygotic isolation in sympatry has become a well-known feature of gamete recognition proteins in marine broadcast spawners. But in most cases the evolutionary process or processes responsible for this pattern have not been identified. Although gamete recognition proteins in C

  13. Reproductive protein evolution in two cryptic species of marine chordate

    Directory of Open Access Journals (Sweden)

    Harrison Richard G

    2011-01-01

    Full Text Available Abstract Background Reproductive character displacement (RCD is a common and taxonomically widespread pattern. In marine broadcast spawning organisms, behavioral and mechanical isolation are absent and prezygotic barriers between species often operate only during the fertilization process. Such barriers are usually a consequence of differences in the way in which sperm and egg proteins interact, so RCD can be manifest as faster evolution of these proteins between species in sympatry than allopatry. Rapid evolution of these proteins often appears to be a consequence of positive (directional selection. Here, we identify a set of candidate gamete recognition proteins (GRPs in the ascidian Ciona intestinalis and showed that these GRPs evolve more rapidly than control proteins (those not involved in gamete recognition. Choosing a subset of these gamete recognition proteins that show evidence of positive selection (CIPRO37.40.1, CIPRO60.5.1, CIPRO100.7.1, we then directly test the RCD hypothesis by comparing divergence (omega and polymorphism (McDonald-Kreitman, Tajima's D, Fu and Li's D and F, Fay and Wu's H statistics in sympatric and allopatric populations of two distinct forms of C. intestinalis (Types A and B between which there are strong post-zygotic barriers. Results Candidate gamete recognition proteins from two lineages of C. intestinalis (Type A and B are evolving more rapidly than control proteins, consistent with patterns seen in insects and mammals. However, ω (dN/dS is not significantly different between the sympatric and allopatric populations, and none of the polymorphism statistics show significant differences between sympatric and allopatric populations. Conclusions Enhanced prezygotic isolation in sympatry has become a well-known feature of gamete recognition proteins in marine broadcast spawners. But in most cases the evolutionary process or processes responsible for this pattern have not been identified. Although gamete

  14. Hidden long evolutionary memory in a model biochemical network

    Science.gov (United States)

    Ali, Md. Zulfikar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

    2018-04-01

    We introduce a minimal model for the evolution of functional protein-interaction networks using a sequence-based mutational algorithm, and apply the model to study neutral drift in networks that yield oscillatory dynamics. Starting with a functional core module, random evolutionary drift increases network complexity even in the absence of specific selective pressures. Surprisingly, we uncover a hidden order in sequence space that gives rise to long-term evolutionary memory, implying strong constraints on network evolution due to the topology of accessible sequence space.

  15. Protein diffusion in photopolymerized poly(ethylene glycol) hydrogel networks

    International Nuclear Information System (INIS)

    Engberg, Kristin; Frank, Curtis W

    2011-01-01

    In this study, protein diffusion through swollen hydrogel networks prepared from end-linked poly(ethylene glycol)-diacrylate (PEG-DA) was investigated. Hydrogels were prepared via photopolymerization from PEG-DA macromonomer solutions of two molecular weights, 4600 Da and 8000 Da, with three initial solid contents: 20, 33 and 50 wt/wt% PEG. Diffusion coefficients for myoglobin traveling across the hydrogel membrane were determined for all PEG network compositions. The diffusion coefficient depended on PEG molecular weight and initial solid content, with the slowest diffusion occurring through lower molecular weight, high-solid-content networks (D gel = 0.16 ± 0.02 x 10 -8 cm 2 s -1 ) and the fastest diffusion occurring through higher molecular weight, low-solid-content networks (D gel = 11.05 ± 0.43 x 10 -8 cm 2 s -1 ). Myoglobin diffusion coefficients increased linearly with the increase of water content within the hydrogels. The permeability of three larger model proteins (horseradish peroxidase, bovine serum albumin and immunoglobulin G) through PEG(8000) hydrogel membranes was also examined, with the observation that globular molecules as large as 10.7 nm in hydrodynamic diameter can diffuse through the PEG network. Protein diffusion coefficients within the PEG hydrogels ranged from one to two orders of magnitude lower than the diffusion coefficients in free water. Network defects were determined to be a significant contributing factor to the observed protein diffusion.

  16. Similar pathogen targets in Arabidopsis thaliana and homo sapiens protein networks.

    Directory of Open Access Journals (Sweden)

    Paulo Shakarian

    Full Text Available We study the behavior of pathogens on host protein networks for humans and Arabidopsis - noting striking similarities. Specifically, we preform [Formula: see text]-shell decomposition analysis on these networks - which groups the proteins into various "shells" based on network structure. We observe that shells with a higher average degree are more highly targeted (with a power-law relationship and that highly targeted nodes lie in shells closer to the inner-core of the network. Additionally, we also note that the inner core of the network is significantly under-targeted. We show that these core proteins may have a role in intra-cellular communication and hypothesize that they are less attacked to ensure survival of the host. This may explain why certain high-degree proteins are not significantly attacked.

  17. Genetic variation shapes protein networks mainly through non-transcriptional mechanisms.

    Directory of Open Access Journals (Sweden)

    Eric J Foss

    2011-09-01

    Full Text Available Networks of co-regulated transcripts in genetically diverse populations have been studied extensively, but little is known about the degree to which these networks cause similar co-variation at the protein level. We quantified 354 proteins in a genetically diverse population of yeast segregants, which allowed for the first time construction of a coherent protein co-variation matrix. We identified tightly co-regulated groups of 36 and 93 proteins that were made up predominantly of genes involved in ribosome biogenesis and amino acid metabolism, respectively. Even though the ribosomal genes were tightly co-regulated at both the protein and transcript levels, genetic regulation of proteins was entirely distinct from that of transcripts, and almost no genes in this network showed a significant correlation between protein and transcript levels. This result calls into question the widely held belief that in yeast, as opposed to higher eukaryotes, ribosomal protein levels are regulated primarily by regulating transcript levels. Furthermore, although genetic regulation of the amino acid network was more similar for proteins and transcripts, regression analysis demonstrated that even here, proteins vary predominantly as a result of non-transcriptional variation. We also found that cis regulation, which is common in the transcriptome, is rare at the level of the proteome. We conclude that most inter-individual variation in levels of these particular high abundance proteins in this genetically diverse population is not caused by variation of their underlying transcripts.

  18. Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks.

    Science.gov (United States)

    Yan, Koon-Kiu; Fang, Gang; Bhardwaj, Nitin; Alexander, Roger P; Gerstein, Mark

    2010-05-18

    The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers' continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems.

  19. Long-Term Evolution of Email Networks: Statistical Regularities, Predictability and Stability of Social Behaviors.

    Science.gov (United States)

    Godoy-Lorite, Antonia; Guimerà, Roger; Sales-Pardo, Marta

    2016-01-01

    In social networks, individuals constantly drop ties and replace them by new ones in a highly unpredictable fashion. This highly dynamical nature of social ties has important implications for processes such as the spread of information or of epidemics. Several studies have demonstrated the influence of a number of factors on the intricate microscopic process of tie replacement, but the macroscopic long-term effects of such changes remain largely unexplored. Here we investigate whether, despite the inherent randomness at the microscopic level, there are macroscopic statistical regularities in the long-term evolution of social networks. In particular, we analyze the email network of a large organization with over 1,000 individuals throughout four consecutive years. We find that, although the evolution of individual ties is highly unpredictable, the macro-evolution of social communication networks follows well-defined statistical patterns, characterized by exponentially decaying log-variations of the weight of social ties and of individuals' social strength. At the same time, we find that individuals have social signatures and communication strategies that are remarkably stable over the scale of several years.

  20. Anomalous diffusion in neutral evolution of model proteins

    Science.gov (United States)

    Nelson, Erik D.; Grishin, Nick V.

    2015-06-01

    Protein evolution is frequently explored using minimalist polymer models, however, little attention has been given to the problem of structural drift, or diffusion. Here, we study neutral evolution of small protein motifs using an off-lattice heteropolymer model in which individual monomers interact as low-resolution amino acids. In contrast to most earlier models, both the length and folded structure of the polymers are permitted to change. To describe structural change, we compute the mean-square distance (MSD) between monomers in homologous folds separated by n neutral mutations. We find that structural change is episodic, and, averaged over lineages (for example, those extending from a single sequence), exhibits a power-law dependence on n . We show that this exponent depends on the alignment method used, and we analyze the distribution of waiting times between neutral mutations. The latter are more disperse than for models required to maintain a specific fold, but exhibit a similar power-law tail.

  1. Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks

    Science.gov (United States)

    White, Forest M.; Wolf-Yadlin, Alejandro

    2016-06-01

    Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.

  2. The relationship among gene expression, the evolution of gene dosage, and the rate of protein evolution.

    Directory of Open Access Journals (Sweden)

    Jean-François Gout

    2010-05-01

    Full Text Available The understanding of selective constraints affecting genes is a major issue in biology. It is well established that gene expression level is a major determinant of the rate of protein evolution, but the reasons for this relationship remain highly debated. Here we demonstrate that gene expression is also a major determinant of the evolution of gene dosage: the rate of gene losses after whole genome duplications in the Paramecium lineage is negatively correlated to the level of gene expression, and this relationship is not a byproduct of other factors known to affect the fate of gene duplicates. This indicates that changes in gene dosage are generally more deleterious for highly expressed genes. This rule also holds for other taxa: in yeast, we find a clear relationship between gene expression level and the fitness impact of reduction in gene dosage. To explain these observations, we propose a model based on the fact that the optimal expression level of a gene corresponds to a trade-off between the benefit and cost of its expression. This COSTEX model predicts that selective pressure against mutations changing gene expression level or affecting the encoded protein should on average be stronger in highly expressed genes and hence that both the frequency of gene loss and the rate of protein evolution should correlate negatively with gene expression. Thus, the COSTEX model provides a simple and common explanation for the general relationship observed between the level of gene expression and the different facets of gene evolution.

  3. SynechoNET: integrated protein-protein interaction database of a model cyanobacterium Synechocystis sp. PCC 6803

    OpenAIRE

    Kim, Woo-Yeon; Kang, Sungsoo; Kim, Byoung-Chul; Oh, Jeehyun; Cho, Seongwoong; Bhak, Jong; Choi, Jong-Soon

    2008-01-01

    Background Cyanobacteria are model organisms for studying photosynthesis, carbon and nitrogen assimilation, evolution of plant plastids, and adaptability to environmental stresses. Despite many studies on cyanobacteria, there is no web-based database of their regulatory and signaling protein-protein interaction networks to date. Description We report a database and website SynechoNET that provides predicted protein-protein interactions. SynechoNET shows cyanobacterial domain-domain interactio...

  4. Moran-evolution of cooperation: From well-mixed to heterogeneous complex networks

    Science.gov (United States)

    Sarkar, Bijan

    2018-05-01

    Configurational arrangement of network architecture and interaction character of individuals are two most influential factors on the mechanisms underlying the evolutionary outcome of cooperation, which is explained by the well-established framework of evolutionary game theory. In the current study, not only qualitatively but also quantitatively, we measure Moran-evolution of cooperation to support an analytical agreement based on the consequences of the replicator equation in a finite population. The validity of the measurement has been double-checked in the well-mixed network by the Langevin stochastic differential equation and the Gillespie-algorithmic version of Moran-evolution, while in a structured network, the measurement of accuracy is verified by the standard numerical simulation. Considering the Birth-Death and Death-Birth updating rules through diffusion of individuals, the investigation is carried out in the wide range of game environments those relate to the various social dilemmas where we are able to draw a new rigorous mathematical track to tackle the heterogeneity of complex networks. The set of modified criteria reveals the exact fact about the emergence and maintenance of cooperation in the structured population. We find that in general, nature promotes the environment of coexistent traits.

  5. Functional modules by relating protein interaction networks and gene expression.

    Science.gov (United States)

    Tornow, Sabine; Mewes, H W

    2003-11-01

    Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression networks. Integrating the information from the different types of networks may lead to the notion of a functional network and functional modules. To find these modules, we propose a new technique which is based on collective, multi-body correlations in a genetic network. We calculated the correlation strength of a group of genes (e.g. in the co-expression network) which were identified as members of a module in a different network (e.g. in the protein interaction network) and estimated the probability that this correlation strength was found by chance. Groups of genes with a significant correlation strength in different networks have a high probability that they perform the same function. Here, we propose evaluating the multi-body correlations by applying the superparamagnetic approach. We compare our method to the presently applied mean Pearson correlations and show that our method is more sensitive in revealing functional relationships.

  6. Semantic integration to identify overlapping functional modules in protein interaction networks

    Directory of Open Access Journals (Sweden)

    Ramanathan Murali

    2007-07-01

    Full Text Available Abstract Background The systematic analysis of protein-protein interactions can enable a better understanding of cellular organization, processes and functions. Functional modules can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of functional module detection algorithms. Results We have developed novel metrics, called semantic similarity and semantic interactivity, which use Gene Ontology (GO annotations to measure the reliability of protein-protein interactions. The protein interaction networks can be converted into a weighted graph representation by assigning the reliability values to each interaction as a weight. We presented a flow-based modularization algorithm to efficiently identify overlapping modules in the weighted interaction networks. The experimental results show that the semantic similarity and semantic interactivity of interacting pairs were positively correlated with functional co-occurrence. The effectiveness of the algorithm for identifying modules was evaluated using functional categories from the MIPS database. We demonstrated that our algorithm had higher accuracy compared to other competing approaches. Conclusion The integration of protein interaction networks with GO annotation data and the capability of detecting overlapping modules substantially improve the accuracy of module identification.

  7. Pervasive Adaptive Evolution in Primate Seminal Proteins.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Seminal fluid proteins show striking effects on reproduction, involving manipulation of female behavior and physiology, mechanisms of sperm competition, and pathogen defense. Strong adaptive pressures are expected for such manifestations of sexual selection and host defense, but the extent of positive selection in seminal fluid proteins from divergent taxa is unknown. We identified adaptive evolution in primate seminal proteins using genomic resources in a tissue-specific study. We found extensive signatures of positive selection when comparing 161 human seminal fluid proteins and 2,858 prostate-expressed genes to those in chimpanzee. Seven of eight outstanding genes yielded statistically significant evidence of positive selection when analyzed in divergent primates. Functional clues were gained through divergent analysis, including several cases of species-specific loss of function in copulatory plug genes, and statistically significant spatial clustering of positively selected sites near the active site of kallikrein 2. This study reveals previously unidentified positive selection in seven primate seminal proteins, and when considered with findings in Drosophila, indicates that extensive positive selection is found in seminal fluid across divergent taxonomic groups.

  8. A tensegrity model for hydrogen bond networks in proteins.

    Science.gov (United States)

    Bywater, Robert P

    2017-05-01

    Hydrogen-bonding networks in proteins considered as structural tensile elements are in balance separately from any other stabilising interactions that may be in operation. The hydrogen bond arrangement in the network is reminiscent of tensegrity structures in architecture and sculpture. Tensegrity has been discussed before in cells and tissues and in proteins. In contrast to previous work only hydrogen bonds are studied here. The other interactions within proteins are either much stronger - covalent bonds connecting the atoms in the molecular skeleton or weaker forces like the so-called hydrophobic interactions. It has been demonstrated that the latter operate independently from hydrogen bonds. Each category of interaction must, if the protein is to have a stable structure, balance out. The hypothesis here is that the entire hydrogen bond network is in balance without any compensating contributions from other types of interaction. For sidechain-sidechain, sidechain-backbone and backbone-backbone hydrogen bonds in proteins, tensegrity balance ("closure") is required over the entire length of the polypeptide chain that defines individually folding units in globular proteins ("domains") as well as within the repeating elements in fibrous proteins that consist of extended chain structures. There is no closure to be found in extended structures that do not have repeating elements. This suggests an explanation as to why globular domains, as well as the repeat units in fibrous proteins, have to have a defined number of residues. Apart from networks of sidechain-sidechain hydrogen bonds there are certain key points at which this closure is achieved in the sidechain-backbone hydrogen bonds and these are associated with demarcation points at the start or end of stretches of secondary structure. Together, these three categories of hydrogen bond achieve the closure that is necessary for the stability of globular protein domains as well as repeating elements in fibrous proteins.

  9. Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Oyang Yen-Jen

    2010-10-01

    Full Text Available Abstract Background Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear. Results We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy. Conclusions We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy.

  10. Accurate detection of hierarchical communities in complex networks based on nonlinear dynamical evolution

    Science.gov (United States)

    Zhuo, Zhao; Cai, Shi-Min; Tang, Ming; Lai, Ying-Cheng

    2018-04-01

    One of the most challenging problems in network science is to accurately detect communities at distinct hierarchical scales. Most existing methods are based on structural analysis and manipulation, which are NP-hard. We articulate an alternative, dynamical evolution-based approach to the problem. The basic principle is to computationally implement a nonlinear dynamical process on all nodes in the network with a general coupling scheme, creating a networked dynamical system. Under a proper system setting and with an adjustable control parameter, the community structure of the network would "come out" or emerge naturally from the dynamical evolution of the system. As the control parameter is systematically varied, the community hierarchies at different scales can be revealed. As a concrete example of this general principle, we exploit clustered synchronization as a dynamical mechanism through which the hierarchical community structure can be uncovered. In particular, for quite arbitrary choices of the nonlinear nodal dynamics and coupling scheme, decreasing the coupling parameter from the global synchronization regime, in which the dynamical states of all nodes are perfectly synchronized, can lead to a weaker type of synchronization organized as clusters. We demonstrate the existence of optimal choices of the coupling parameter for which the synchronization clusters encode accurate information about the hierarchical community structure of the network. We test and validate our method using a standard class of benchmark modular networks with two distinct hierarchies of communities and a number of empirical networks arising from the real world. Our method is computationally extremely efficient, eliminating completely the NP-hard difficulty associated with previous methods. The basic principle of exploiting dynamical evolution to uncover hidden community organizations at different scales represents a "game-change" type of approach to addressing the problem of community

  11. MetaGO: Predicting Gene Ontology of Non-homologous Proteins Through Low-Resolution Protein Structure Prediction and Protein-Protein Network Mapping.

    Science.gov (United States)

    Zhang, Chengxin; Zheng, Wei; Freddolino, Peter L; Zhang, Yang

    2018-03-10

    Homology-based transferal remains the major approach to computational protein function annotations, but it becomes increasingly unreliable when the sequence identity between query and template decreases below 30%. We propose a novel pipeline, MetaGO, to deduce Gene Ontology attributes of proteins by combining sequence homology-based annotation with low-resolution structure prediction and comparison, and partner's homology-based protein-protein network mapping. The pipeline was tested on a large-scale set of 1000 non-redundant proteins from the CAFA3 experiment. Under the stringent benchmark conditions where templates with >30% sequence identity to the query are excluded, MetaGO achieves average F-measures of 0.487, 0.408, and 0.598, for Molecular Function, Biological Process, and Cellular Component, respectively, which are significantly higher than those achieved by other state-of-the-art function annotations methods. Detailed data analysis shows that the major advantage of the MetaGO lies in the new functional homolog detections from partner's homology-based network mapping and structure-based local and global structure alignments, the confidence scores of which can be optimally combined through logistic regression. These data demonstrate the power of using a hybrid model incorporating protein structure and interaction networks to deduce new functional insights beyond traditional sequence homology-based referrals, especially for proteins that lack homologous function templates. The MetaGO pipeline is available at http://zhanglab.ccmb.med.umich.edu/MetaGO/. Copyright © 2018. Published by Elsevier Ltd.

  12. Understanding the process of social network evolution: Online-offline integrated analysis of social tie formation.

    Science.gov (United States)

    Kwak, Doyeon; Kim, Wonjoon

    2017-01-01

    It is important to consider the interweaving nature of online and offline social networks when we examine social network evolution. However, it is difficult to find any research that examines the process of social tie formation from an integrated perspective. In our study, we quantitatively measure offline interactions and examine the corresponding evolution of online social network in order to understand the significance of interrelationship between online and offline social factors in generating social ties. We analyze the radio signal strength indicator sensor data from a series of social events to understand offline interactions among the participants and measure the structural attributes of their existing online Facebook social networks. By monitoring the changes in their online social networks before and after offline interactions in a series of social events, we verify that the ability to develop an offline interaction into an online friendship is tied to the number of social connections that participants previously had, while the presence of shared mutual friends between a pair of participants disrupts potential new connections within the pre-designed offline social events. Thus, while our integrative approach enables us to confirm the theory of preferential attachment in the process of network formation, the common neighbor theory is not supported. Our dual-dimensional network analysis allows us to observe the actual process of social network evolution rather than to make predictions based on the assumption of self-organizing networks.

  13. Understanding the process of social network evolution: Online-offline integrated analysis of social tie formation.

    Directory of Open Access Journals (Sweden)

    Doyeon Kwak

    Full Text Available It is important to consider the interweaving nature of online and offline social networks when we examine social network evolution. However, it is difficult to find any research that examines the process of social tie formation from an integrated perspective. In our study, we quantitatively measure offline interactions and examine the corresponding evolution of online social network in order to understand the significance of interrelationship between online and offline social factors in generating social ties. We analyze the radio signal strength indicator sensor data from a series of social events to understand offline interactions among the participants and measure the structural attributes of their existing online Facebook social networks. By monitoring the changes in their online social networks before and after offline interactions in a series of social events, we verify that the ability to develop an offline interaction into an online friendship is tied to the number of social connections that participants previously had, while the presence of shared mutual friends between a pair of participants disrupts potential new connections within the pre-designed offline social events. Thus, while our integrative approach enables us to confirm the theory of preferential attachment in the process of network formation, the common neighbor theory is not supported. Our dual-dimensional network analysis allows us to observe the actual process of social network evolution rather than to make predictions based on the assumption of self-organizing networks.

  14. Co-evolution of SNF spliceosomal proteins with their RNA targets in trans-splicing nematodes.

    Science.gov (United States)

    Strange, Rex Meade; Russelburg, L Peyton; Delaney, Kimberly J

    2016-08-01

    Although the mechanism of pre-mRNA splicing has been well characterized, the evolution of spliceosomal proteins is poorly understood. The U1A/U2B″/SNF family (hereafter referred to as the SNF family) of RNA binding spliceosomal proteins participates in both the U1 and U2 small interacting nuclear ribonucleoproteins (snRNPs). The highly constrained nature of this system has inhibited an analysis of co-evolutionary trends between the proteins and their RNA binding targets. Here we report accelerated sequence evolution in the SNF protein family in Phylum Nematoda, which has allowed an analysis of protein:RNA co-evolution. In a comparison of SNF genes from ecdysozoan species, we found a correlation between trans-splicing species (nematodes) and increased phylogenetic branch lengths of the SNF protein family, with respect to their sister clade Arthropoda. In particular, we found that nematodes (~70-80 % of pre-mRNAs are trans-spliced) have experienced higher rates of SNF sequence evolution than arthropods (predominantly cis-spliced) at both the nucleotide and amino acid levels. Interestingly, this increased evolutionary rate correlates with the reliance on trans-splicing by nematodes, which would alter the role of the SNF family of spliceosomal proteins. We mapped amino acid substitutions to functionally important regions of the SNF protein, specifically to sites that are predicted to disrupt protein:RNA and protein:protein interactions. Finally, we investigated SNF's RNA targets: the U1 and U2 snRNAs. Both are more divergent in nematodes than arthropods, suggesting the RNAs have co-evolved with SNF in order to maintain the necessarily high affinity interaction that has been characterized in other species.

  15. Protein evolution via amino acid and codon elimination

    DEFF Research Database (Denmark)

    Goltermann, Lise; Larsen, Marie Sofie Yoo; Banerjee, Rajat

    2010-01-01

    BACKGROUND: Global residue-specific amino acid mutagenesis can provide important biological insight and generate proteins with altered properties, but at the risk of protein misfolding. Further, targeted libraries are usually restricted to a handful of amino acids because there is an exponential...... correlation between the number of residues randomized and the size of the resulting ensemble. Using GFP as the model protein, we present a strategy, termed protein evolution via amino acid and codon elimination, through which simplified, native-like polypeptides encoded by a reduced genetic code were obtained...... simultaneously), while retaining varying levels of activity. Combination of these substitutions to generate a Phe-free variant of GFP abolished fluorescence. Combinatorial re-introduction of five Phe residues, based on the activities of the respective single amino acid replacements, was sufficient to restore GFP...

  16. Expanding protein universe and its origin from the biological Big Bang.

    Science.gov (United States)

    Dokholyan, Nikolay V; Shakhnovich, Boris; Shakhnovich, Eugene I

    2002-10-29

    The bottom-up approach to understanding the evolution of organisms is by studying molecular evolution. With the large number of protein structures identified in the past decades, we have discovered peculiar patterns that nature imprints on protein structural space in the course of evolution. In particular, we have discovered that the universe of protein structures is organized hierarchically into a scale-free network. By understanding the cause of these patterns, we attempt to glance at the very origin of life.

  17. Identifiability of tree-child phylogenetic networks under a probabilistic recombination-mutation model of evolution.

    Science.gov (United States)

    Francis, Andrew; Moulton, Vincent

    2018-06-07

    Phylogenetic networks are an extension of phylogenetic trees which are used to represent evolutionary histories in which reticulation events (such as recombination and hybridization) have occurred. A central question for such networks is that of identifiability, which essentially asks under what circumstances can we reliably identify the phylogenetic network that gave rise to the observed data? Recently, identifiability results have appeared for networks relative to a model of sequence evolution that generalizes the standard Markov models used for phylogenetic trees. However, these results are quite limited in terms of the complexity of the networks that are considered. In this paper, by introducing an alternative probabilistic model for evolution along a network that is based on some ground-breaking work by Thatte for pedigrees, we are able to obtain an identifiability result for a much larger class of phylogenetic networks (essentially the class of so-called tree-child networks). To prove our main theorem, we derive some new results for identifying tree-child networks combinatorially, and then adapt some techniques developed by Thatte for pedigrees to show that our combinatorial results imply identifiability in the probabilistic setting. We hope that the introduction of our new model for networks could lead to new approaches to reliably construct phylogenetic networks. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. A genotype network reveals homoplastic cycles of convergent evolution in influenza A (H3N2) haemagglutinin.

    Science.gov (United States)

    Wagner, Andreas

    2014-07-07

    Networks of evolving genotypes can be constructed from the worldwide time-resolved genotyping of pathogens like influenza viruses. Such genotype networks are graphs where neighbouring vertices (viral strains) differ in a single nucleotide or amino acid. A rich trove of network analysis methods can help understand the evolutionary dynamics reflected in the structure of these networks. Here, I analyse a genotype network comprising hundreds of influenza A (H3N2) haemagglutinin genes. The network is rife with cycles that reflect non-random parallel or convergent (homoplastic) evolution. These cycles also show patterns of sequence change characteristic for strong and local evolutionary constraints, positive selection and mutation-limited evolution. Such cycles would not be visible on a phylogenetic tree, illustrating that genotype network analysis can complement phylogenetic analyses. The network also shows a distinct modular or community structure that reflects temporal more than spatial proximity of viral strains, where lowly connected bridge strains connect different modules. These and other organizational patterns illustrate that genotype networks can help us study evolution in action at an unprecedented level of resolution. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  19. Intelligent Resource Management for Local Area Networks: Approach and Evolution

    Science.gov (United States)

    Meike, Roger

    1988-01-01

    The Data Management System network is a complex and important part of manned space platforms. Its efficient operation is vital to crew, subsystems and experiments. AI is being considered to aid in the initial design of the network and to augment the management of its operation. The Intelligent Resource Management for Local Area Networks (IRMA-LAN) project is concerned with the application of AI techniques to network configuration and management. A network simulation was constructed employing real time process scheduling for realistic loads, and utilizing the IEEE 802.4 token passing scheme. This simulation is an integral part of the construction of the IRMA-LAN system. From it, a causal model is being constructed for use in prediction and deep reasoning about the system configuration. An AI network design advisor is being added to help in the design of an efficient network. The AI portion of the system is planned to evolve into a dynamic network management aid. The approach, the integrated simulation, project evolution, and some initial results are described.

  20. Topological and functional properties of the small GTPases protein interaction network.

    Directory of Open Access Journals (Sweden)

    Anna Delprato

    Full Text Available Small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran regulate key cellular processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. A great deal of experimental evidence supports the existence of signaling cascades and feedback loops within and among the small GTPase subfamilies suggesting that these proteins function in a coordinated and cooperative manner. The interplay occurs largely through association with bi-partite regulatory and effector proteins but can also occur through the active form of the small GTPases themselves. In order to understand the connectivity of the small GTPases signaling routes, a systems-level approach that analyzes data describing direct and indirect interactions was used to construct the small GTPases protein interaction network. The data were curated from the Search Tool for the Retrieval of Interacting Genes (STRING database and include only experimentally validated interactions. The network method enables the conceptualization of the overall structure as well as the underlying organization of the protein-protein interactions. The interaction network described here is comprised of 778 nodes and 1943 edges and has a scale-free topology. Rac1, Cdc42, RhoA, and HRas are identified as the hubs. Ten sub-network motifs are also identified in this study with themes in apoptosis, cell growth/proliferation, vesicle traffic, cell adhesion/junction dynamics, the nicotinamide adenine dinucleotide phosphate (NADPH oxidase response, transcription regulation, receptor-mediated endocytosis, gene silencing, and growth factor signaling. Bottleneck proteins that bridge signaling paths and proteins that overlap in multiple small GTPase networks are described along with the functional annotation of all proteins in the network.

  1. On the Adaptive Design Rules of Biochemical Networks in Evolution

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2007-01-01

    Full Text Available Biochemical networks are the backbones of physiological systems of organisms. Therefore, a biochemical network should be sufficiently robust (not sensitive to tolerate genetic mutations and environmental changes in the evolutionary process. In this study, based on the robustness and sensitivity criteria of biochemical networks, the adaptive design rules are developed for natural selection in the evolutionary process. This will provide insights into the robust adaptive mechanism of biochemical networks in the evolutionary process. We find that if a mutated biochemical network satisfies the robustness and sensitivity criteria of natural selection, there is a high probability for the biochemical network to prevail during natural selection in the evolutionary process. Since there are various mutated biochemical networks that can satisfy these criteria but have some differences in phenotype, the biochemical networks increase their diversities in the evolutionary process. The robustness of a biochemical network enables co-option so that new phenotypes can be generated in evolution. The proposed robust adaptive design rules of natural selection gain much insight into the evolutionary mechanism and provide a systematic robust biochemical circuit design method of biochemical networks for biotechnological and therapeutic purposes in the future.

  2. Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

    Science.gov (United States)

    Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

    2011-11-01

    A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

  3. Neuron-Like Networks Between Ribosomal Proteins Within the Ribosome

    Science.gov (United States)

    Poirot, Olivier; Timsit, Youri

    2016-05-01

    From brain to the World Wide Web, information-processing networks share common scale invariant properties. Here, we reveal the existence of neural-like networks at a molecular scale within the ribosome. We show that with their extensions, ribosomal proteins form complex assortative interaction networks through which they communicate through tiny interfaces. The analysis of the crystal structures of 50S eubacterial particles reveals that most of these interfaces involve key phylogenetically conserved residues. The systematic observation of interactions between basic and aromatic amino acids at the interfaces and along the extension provides new structural insights that may contribute to decipher the molecular mechanisms of signal transmission within or between the ribosomal proteins. Similar to neurons interacting through “molecular synapses”, ribosomal proteins form a network that suggest an analogy with a simple molecular brain in which the “sensory-proteins” innervate the functional ribosomal sites, while the “inter-proteins” interconnect them into circuits suitable to process the information flow that circulates during protein synthesis. It is likely that these circuits have evolved to coordinate both the complex macromolecular motions and the binding of the multiple factors during translation. This opens new perspectives on nanoscale information transfer and processing.

  4. Time evolution of Wikipedia network ranking

    Science.gov (United States)

    Eom, Young-Ho; Frahm, Klaus M.; Benczúr, András; Shepelyansky, Dima L.

    2013-12-01

    We study the time evolution of ranking and spectral properties of the Google matrix of English Wikipedia hyperlink network during years 2003-2011. The statistical properties of ranking of Wikipedia articles via PageRank and CheiRank probabilities, as well as the matrix spectrum, are shown to be stabilized for 2007-2011. A special emphasis is done on ranking of Wikipedia personalities and universities. We show that PageRank selection is dominated by politicians while 2DRank, which combines PageRank and CheiRank, gives more accent on personalities of arts. The Wikipedia PageRank of universities recovers 80% of top universities of Shanghai ranking during the considered time period.

  5. Network evolution driven by dynamics applied to graph coloring

    International Nuclear Information System (INIS)

    Wu Jian-She; Li Li-Guang; Yu Xin; Jiao Li-Cheng; Wang Xiao-Hua

    2013-01-01

    An evolutionary network driven by dynamics is studied and applied to the graph coloring problem. From an initial structure, both the topology and the coupling weights evolve according to the dynamics. On the other hand, the dynamics of the network are determined by the topology and the coupling weights, so an interesting structure-dynamics co-evolutionary scheme appears. By providing two evolutionary strategies, a network described by the complement of a graph will evolve into several clusters of nodes according to their dynamics. The nodes in each cluster can be assigned the same color and nodes in different clusters assigned different colors. In this way, a co-evolution phenomenon is applied to the graph coloring problem. The proposed scheme is tested on several benchmark graphs for graph coloring

  6. Prediction of protein hydration sites from sequence by modular neural networks

    DEFF Research Database (Denmark)

    Ehrlich, L.; Reczko, M.; Bohr, Henrik

    1998-01-01

    The hydration properties of a protein are important determinants of its structure and function. Here, modular neural networks are employed to predict ordered hydration sites using protein sequence information. First, secondary structure and solvent accessibility are predicted from sequence with two...... separate neural networks. These predictions are used as input together with protein sequences for networks predicting hydration of residues, backbone atoms and sidechains. These networks are teined with protein crystal structures. The prediction of hydration is improved by adding information on secondary...... structure and solvent accessibility and, using actual values of these properties, redidue hydration can be predicted to 77% accuracy with a Metthews coefficient of 0.43. However, predicted property data with an accuracy of 60-70% result in less than half the improvement in predictive performance observed...

  7. Building and analyzing protein interactome networks by cross-species comparisons

    Directory of Open Access Journals (Sweden)

    Blackman Barron

    2010-03-01

    Full Text Available Abstract Background A genomic catalogue of protein-protein interactions is a rich source of information, particularly for exploring the relationships between proteins. Numerous systems-wide and small-scale experiments have been conducted to identify interactions; however, our knowledge of all interactions for any one species is incomplete, and alternative means to expand these network maps is needed. We therefore took a comparative biology approach to predict protein-protein interactions across five species (human, mouse, fly, worm, and yeast and developed InterologFinder for research biologists to easily navigate this data. We also developed a confidence score for interactions based on available experimental evidence and conservation across species. Results The connectivity of the resultant networks was determined to have scale-free distribution, small-world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen and to assign new function to proteins. Predicted interactions within this dataset were tested by co-immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced. Conclusions Protein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our website http://www.interologfinder.org provides research biologists intuitive access to this data.

  8. Aligning Biomolecular Networks Using Modular Graph Kernels

    Science.gov (United States)

    Towfic, Fadi; Greenlee, M. Heather West; Honavar, Vasant

    Comparative analysis of biomolecular networks constructed using measurements from different conditions, tissues, and organisms offer a powerful approach to understanding the structure, function, dynamics, and evolution of complex biological systems. We explore a class of algorithms for aligning large biomolecular networks by breaking down such networks into subgraphs and computing the alignment of the networks based on the alignment of their subgraphs. The resulting subnetworks are compared using graph kernels as scoring functions. We provide implementations of the resulting algorithms as part of BiNA, an open source biomolecular network alignment toolkit. Our experiments using Drosophila melanogaster, Saccharomyces cerevisiae, Mus musculus and Homo sapiens protein-protein interaction networks extracted from the DIP repository of protein-protein interaction data demonstrate that the performance of the proposed algorithms (as measured by % GO term enrichment of subnetworks identified by the alignment) is competitive with some of the state-of-the-art algorithms for pair-wise alignment of large protein-protein interaction networks. Our results also show that the inter-species similarity scores computed based on graph kernels can be used to cluster the species into a species tree that is consistent with the known phylogenetic relationships among the species.

  9. Cross-over between discrete and continuous protein structure space: insights into automatic classification and networks of protein structures.

    Directory of Open Access Journals (Sweden)

    Alberto Pascual-García

    2009-03-01

    Full Text Available Structural classifications of proteins assume the existence of the fold, which is an intrinsic equivalence class of protein domains. Here, we test in which conditions such an equivalence class is compatible with objective similarity measures. We base our analysis on the transitive property of the equivalence relationship, requiring that similarity of A with B and B with C implies that A and C are also similar. Divergent gene evolution leads us to expect that the transitive property should approximately hold. However, if protein domains are a combination of recurrent short polypeptide fragments, as proposed by several authors, then similarity of partial fragments may violate the transitive property, favouring the continuous view of the protein structure space. We propose a measure to quantify the violations of the transitive property when a clustering algorithm joins elements into clusters, and we find out that such violations present a well defined and detectable cross-over point, from an approximately transitive regime at high structure similarity to a regime with large transitivity violations and large differences in length at low similarity. We argue that protein structure space is discrete and hierarchic classification is justified up to this cross-over point, whereas at lower similarities the structure space is continuous and it should be represented as a network. We have tested the qualitative behaviour of this measure, varying all the choices involved in the automatic classification procedure, i.e., domain decomposition, alignment algorithm, similarity score, and clustering algorithm, and we have found out that this behaviour is quite robust. The final classification depends on the chosen algorithms. We used the values of the clustering coefficient and the transitivity violations to select the optimal choices among those that we tested. Interestingly, this criterion also favours the agreement between automatic and expert classifications

  10. The organisational structure of protein networks: revisiting the centrality-lethality hypothesis.

    Science.gov (United States)

    Raman, Karthik; Damaraju, Nandita; Joshi, Govind Krishna

    2014-03-01

    Protein networks, describing physical interactions as well as functional associations between proteins, have been unravelled for many organisms in the recent past. Databases such as the STRING provide excellent resources for the analysis of such networks. In this contribution, we revisit the organisation of protein networks, particularly the centrality-lethality hypothesis, which hypothesises that nodes with higher centrality in a network are more likely to produce lethal phenotypes on removal, compared to nodes with lower centrality. We consider the protein networks of a diverse set of 20 organisms, with essentiality information available in the Database of Essential Genes and assess the relationship between centrality measures and lethality. For each of these organisms, we obtained networks of high-confidence interactions from the STRING database, and computed network parameters such as degree, betweenness centrality, closeness centrality and pairwise disconnectivity indices. We observe that the networks considered here are predominantly disassortative. Further, we observe that essential nodes in a network have a significantly higher average degree and betweenness centrality, compared to the network average. Most previous studies have evaluated the centrality-lethality hypothesis for Saccharomyces cerevisiae and Escherichia coli; we here observe that the centrality-lethality hypothesis hold goods for a large number of organisms, with certain limitations. Betweenness centrality may also be a useful measure to identify essential nodes, but measures like closeness centrality and pairwise disconnectivity are not significantly higher for essential nodes.

  11. Exploring hierarchical and overlapping modular structure in the yeast protein interaction network

    Directory of Open Access Journals (Sweden)

    Zhao Yi

    2010-12-01

    Full Text Available Abstract Background Developing effective strategies to reveal modular structures in protein interaction networks is crucial for better understanding of molecular mechanisms of underlying biological processes. In this paper, we propose a new density-based algorithm (ADHOC for clustering vertices of a protein interaction network using a novel subgraph density measurement. Results By statistically evaluating several independent criteria, we found that ADHOC could significantly improve the outcome as compared with five previously reported density-dependent methods. We further applied ADHOC to investigate the hierarchical and overlapping modular structure in the yeast PPI network. Our method could effectively detect both protein modules and the overlaps between them, and thus greatly promote the precise prediction of protein functions. Moreover, by further assaying the intermodule layer of the yeast PPI network, we classified hubs into two types, module hubs and inter-module hubs. Each type presents distinct characteristics both in network topology and biological functions, which could conduce to the better understanding of relationship between network architecture and biological implications. Conclusions Our proposed algorithm based on the novel subgraph density measurement makes it possible to more precisely detect hierarchical and overlapping modular structures in protein interaction networks. In addition, our method also shows a strong robustness against the noise in network, which is quite critical for analyzing such a high noise network.

  12. A tensegrity model for hydrogen bond networks in proteins

    Directory of Open Access Journals (Sweden)

    Robert P. Bywater

    2017-05-01

    Full Text Available Hydrogen-bonding networks in proteins considered as structural tensile elements are in balance separately from any other stabilising interactions that may be in operation. The hydrogen bond arrangement in the network is reminiscent of tensegrity structures in architecture and sculpture. Tensegrity has been discussed before in cells and tissues and in proteins. In contrast to previous work only hydrogen bonds are studied here. The other interactions within proteins are either much stronger − covalent bonds connecting the atoms in the molecular skeleton or weaker forces like the so-called hydrophobic interactions. It has been demonstrated that the latter operate independently from hydrogen bonds. Each category of interaction must, if the protein is to have a stable structure, balance out. The hypothesis here is that the entire hydrogen bond network is in balance without any compensating contributions from other types of interaction. For sidechain-sidechain, sidechain-backbone and backbone-backbone hydrogen bonds in proteins, tensegrity balance (“closure” is required over the entire length of the polypeptide chain that defines individually folding units in globular proteins (“domains” as well as within the repeating elements in fibrous proteins that consist of extended chain structures. There is no closure to be found in extended structures that do not have repeating elements. This suggests an explanation as to why globular domains, as well as the repeat units in fibrous proteins, have to have a defined number of residues. Apart from networks of sidechain-sidechain hydrogen bonds there are certain key points at which this closure is achieved in the sidechain-backbone hydrogen bonds and these are associated with demarcation points at the start or end of stretches of secondary structure. Together, these three categories of hydrogen bond achieve the closure that is necessary for the stability of globular protein domains as well as repeating

  13. The construction of an amino acid network for understanding protein structure and function.

    Science.gov (United States)

    Yan, Wenying; Zhou, Jianhong; Sun, Maomin; Chen, Jiajia; Hu, Guang; Shen, Bairong

    2014-06-01

    Amino acid networks (AANs) are undirected networks consisting of amino acid residues and their interactions in three-dimensional protein structures. The analysis of AANs provides novel insight into protein science, and several common amino acid network properties have revealed diverse classes of proteins. In this review, we first summarize methods for the construction and characterization of AANs. We then compare software tools for the construction and analysis of AANs. Finally, we review the application of AANs for understanding protein structure and function, including the identification of functional residues, the prediction of protein folding, analyzing protein stability and protein-protein interactions, and for understanding communication within and between proteins.

  14. Biophysical and structural considerations for protein sequence evolution

    Directory of Open Access Journals (Sweden)

    Grahnen Johan A

    2011-12-01

    Full Text Available Abstract Background Protein sequence evolution is constrained by the biophysics of folding and function, causing interdependence between interacting sites in the sequence. However, current site-independent models of sequence evolutions do not take this into account. Recent attempts to integrate the influence of structure and biophysics into phylogenetic models via statistical/informational approaches have not resulted in expected improvements in model performance. This suggests that further innovations are needed for progress in this field. Results Here we develop a coarse-grained physics-based model of protein folding and binding function, and compare it to a popular informational model. We find that both models violate the assumption of the native sequence being close to a thermodynamic optimum, causing directional selection away from the native state. Sampling and simulation show that the physics-based model is more specific for fold-defining interactions that vary less among residue type. The informational model diffuses further in sequence space with fewer barriers and tends to provide less support for an invariant sites model, although amino acid substitutions are generally conservative. Both approaches produce sequences with natural features like dN/dS Conclusions Simple coarse-grained models of protein folding can describe some natural features of evolving proteins but are currently not accurate enough to use in evolutionary inference. This is partly due to improper packing of the hydrophobic core. We suggest possible improvements on the representation of structure, folding energy, and binding function, as regards both native and non-native conformations, and describe a large number of possible applications for such a model.

  15. Effects of biases in domain wall network evolution. II. Quantitative analysis

    Science.gov (United States)

    Correia, J. R. C. C. C.; Leite, I. S. C. R.; Martins, C. J. A. P.

    2018-04-01

    Domain walls form at phase transitions which break discrete symmetries. In a cosmological context, they often overclose the Universe (contrary to observational evidence), although one may prevent this by introducing biases or forcing anisotropic evolution of the walls. In a previous work [Correia et al., Phys. Rev. D 90, 023521 (2014), 10.1103/PhysRevD.90.023521], we numerically studied the evolution of various types of biased domain wall networks in the early Universe, confirming that anisotropic networks ultimately reach scaling while those with a biased potential or biased initial conditions decay. We also found that the analytic decay law obtained by Hindmarsh was in good agreement with simulations of biased potentials, but not of biased initial conditions, and suggested that the difference was related to the Gaussian approximation underlying the analytic law. Here, we extend our previous work in several ways. For the cases of biased potential and biased initial conditions, we study in detail the field distributions in the simulations, confirming that the validity (or not) of the Gaussian approximation is the key difference between the two cases. For anisotropic walls, we carry out a more extensive set of numerical simulations and compare them to the canonical velocity-dependent one-scale model for domain walls, finding that the model accurately predicts the linear scaling regime after isotropization. Overall, our analysis provides a quantitative description of the cosmological evolution of these networks.

  16. The function of communities in protein interaction networks at multiple scales

    Directory of Open Access Journals (Sweden)

    Jones Nick S

    2010-07-01

    Full Text Available Abstract Background If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network. Results Our results demonstrate that the functional homogeneity of communities depends on the scale selected, and that almost all proteins lie in a functionally homogeneous community at some scale. We judge functional homogeneity using a novel test and three independent characterizations of protein function, and find a high degree of overlap between these measures. We show that a high mean clustering coefficient of a community can be used to identify those that are functionally homogeneous. By tracing the community membership of a protein through multiple scales we demonstrate how our approach could be useful to biologists focusing on a particular protein. Conclusions We show that there is no one scale of interest in the community structure of the yeast protein interaction network, but we can identify the range of resolution parameters that yield the most functionally coherent communities, and predict which communities are most likely to be functionally homogeneous.

  17. Convergent evolution of modularity in metabolic networks through different community structures

    Directory of Open Access Journals (Sweden)

    Zhou Wanding

    2012-09-01

    Full Text Available Abstract Background It has been reported that the modularity of metabolic networks of bacteria is closely related to the variability of their living habitats. However, given the dependency of the modularity score on the community structure, it remains unknown whether organisms achieve certain modularity via similar or different community structures. Results In this work, we studied the relationship between similarities in modularity scores and similarities in community structures of the metabolic networks of 1021 species. Both similarities are then compared against the genetic distances. We revisited the association between modularity and variability of the microbial living environments and extended the analysis to other aspects of their life style such as temperature and oxygen requirements. We also tested both topological and biological intuition of the community structures identified and investigated the extent of their conservation with respect to the taxomony. Conclusions We find that similar modularities are realized by different community structures. We find that such convergent evolution of modularity is closely associated with the number of (distinct enzymes in the organism’s metabolome, a consequence of different life styles of the species. We find that the order of modularity is the same as the order of the number of the enzymes under the classification based on the temperature preference but not on the oxygen requirement. Besides, inspection of modularity-based communities reveals that these communities are graph-theoretically meaningful yet not reflective of specific biological functions. From an evolutionary perspective, we find that the community structures are conserved only at the level of kingdoms. Our results call for more investigation into the interplay between evolution and modularity: how evolution shapes modularity, and how modularity affects evolution (mainly in terms of fitness and evolvability. Further, our results

  18. Convergent evolution of modularity in metabolic networks through different community structures.

    Science.gov (United States)

    Zhou, Wanding; Nakhleh, Luay

    2012-09-14

    It has been reported that the modularity of metabolic networks of bacteria is closely related to the variability of their living habitats. However, given the dependency of the modularity score on the community structure, it remains unknown whether organisms achieve certain modularity via similar or different community structures. In this work, we studied the relationship between similarities in modularity scores and similarities in community structures of the metabolic networks of 1021 species. Both similarities are then compared against the genetic distances. We revisited the association between modularity and variability of the microbial living environments and extended the analysis to other aspects of their life style such as temperature and oxygen requirements. We also tested both topological and biological intuition of the community structures identified and investigated the extent of their conservation with respect to the taxonomy. We find that similar modularities are realized by different community structures. We find that such convergent evolution of modularity is closely associated with the number of (distinct) enzymes in the organism's metabolome, a consequence of different life styles of the species. We find that the order of modularity is the same as the order of the number of the enzymes under the classification based on the temperature preference but not on the oxygen requirement. Besides, inspection of modularity-based communities reveals that these communities are graph-theoretically meaningful yet not reflective of specific biological functions. From an evolutionary perspective, we find that the community structures are conserved only at the level of kingdoms. Our results call for more investigation into the interplay between evolution and modularity: how evolution shapes modularity, and how modularity affects evolution (mainly in terms of fitness and evolvability). Further, our results call for exploring new measures of modularity and network

  19. msiDBN: A Method of Identifying Critical Proteins in Dynamic PPI Networks

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2014-01-01

    Full Text Available Dynamics of protein-protein interactions (PPIs reveals the recondite principles of biological processes inside a cell. Shown in a wealth of study, just a small group of proteins, rather than the majority, play more essential roles at crucial points of biological processes. This present work focuses on identifying these critical proteins exhibiting dramatic structural changes in dynamic PPI networks. First, a comprehensive way of modeling the dynamic PPIs is presented which simultaneously analyzes the activity of proteins and assembles the dynamic coregulation correlation between proteins at each time point. Second, a novel method is proposed, named msiDBN, which models a common representation of multiple PPI networks using a deep belief network framework and analyzes the reconstruction errors and the variabilities across the time courses in the biological process. Experiments were implemented on data of yeast cell cycles. We evaluated our network construction method by comparing the functional representations of the derived networks with two other traditional construction methods. The ranking results of critical proteins in msiDBN were compared with the results from the baseline methods. The results of comparison showed that msiDBN had better reconstruction rate and identified more proteins of critical value to yeast cell cycle process.

  20. Exploring the evolution of node neighborhoods in Dynamic Networks

    Science.gov (United States)

    Orman, Günce Keziban; Labatut, Vincent; Naskali, Ahmet Teoman

    2017-09-01

    Dynamic Networks are a popular way of modeling and studying the behavior of evolving systems. However, their analysis constitutes a relatively recent subfield of Network Science, and the number of available tools is consequently much smaller than for static networks. In this work, we propose a method specifically designed to take advantage of the longitudinal nature of dynamic networks. It characterizes each individual node by studying the evolution of its direct neighborhood, based on the assumption that the way this neighborhood changes reflects the role and position of the node in the whole network. For this purpose, we define the concept of neighborhood event, which corresponds to the various transformations such groups of nodes can undergo, and describe an algorithm for detecting such events. We demonstrate the interest of our method on three real-world networks: DBLP, LastFM and Enron. We apply frequent pattern mining to extract meaningful information from temporal sequences of neighborhood events. This results in the identification of behavioral trends emerging in the whole network, as well as the individual characterization of specific nodes. We also perform a cluster analysis, which reveals that, in all three networks, one can distinguish two types of nodes exhibiting different behaviors: a very small group of active nodes, whose neighborhood undergo diverse and frequent events, and a very large group of stable nodes.

  1. A human protein interaction network shows conservation of aging processes between human and invertebrate species.

    Directory of Open Access Journals (Sweden)

    Russell Bell

    2009-03-01

    Full Text Available We have mapped a protein interaction network of human homologs of proteins that modify longevity in invertebrate species. This network is derived from a proteome-scale human protein interaction Core Network generated through unbiased high-throughput yeast two-hybrid searches. The longevity network is composed of 175 human homologs of proteins known to confer increased longevity through loss of function in yeast, nematode, or fly, and 2,163 additional human proteins that interact with these homologs. Overall, the network consists of 3,271 binary interactions among 2,338 unique proteins. A comparison of the average node degree of the human longevity homologs with random sets of proteins in the Core Network indicates that human homologs of longevity proteins are highly connected hubs with a mean node degree of 18.8 partners. Shortest path length analysis shows that proteins in this network are significantly more connected than would be expected by chance. To examine the relationship of this network to human aging phenotypes, we compared the genes encoding longevity network proteins to genes known to be changed transcriptionally during aging in human muscle. In the case of both the longevity protein homologs and their interactors, we observed enrichments for differentially expressed genes in the network. To determine whether homologs of human longevity interacting proteins can modulate life span in invertebrates, homologs of 18 human FRAP1 interacting proteins showing significant changes in human aging muscle were tested for effects on nematode life span using RNAi. Of 18 genes tested, 33% extended life span when knocked-down in Caenorhabditis elegans. These observations indicate that a broad class of longevity genes identified in invertebrate models of aging have relevance to human aging. They also indicate that the longevity protein interaction network presented here is enriched for novel conserved longevity proteins.

  2. Finite size effects and symmetry breaking in the evolution of networks of competing Boolean nodes

    International Nuclear Information System (INIS)

    Liu, M; Bassler, K E

    2011-01-01

    Finite size effects on the evolutionary dynamics of Boolean networks are analyzed. In the model considered, Boolean networks evolve via a competition between nodes that punishes those in the majority. Previous studies have found that large networks evolve to a statistical steady state that is both critical and highly canalized, and that the evolution of canalization, which is a form of robustness found in genetic regulatory networks, is associated with a particular symmetry of the evolutionary dynamics. Here, it is found that finite size networks evolve in a fundamentally different way than infinitely large networks do. The symmetry of the evolutionary dynamics of infinitely large networks that selects for canalizing Boolean functions is broken in the evolutionary dynamics of finite size networks. In finite size networks, there is an additional selection for input-inverting Boolean functions that output a value opposite to the majority of input values. The reason for the symmetry breaking in the evolutionary dynamics is found to be due to the need for nodes in finite size networks to behave differently in order to cooperate so that the system collectively performs as efficiently as possible. The results suggest that both finite size effects and symmetry are fundamental for understanding the evolution of real-world complex networks, including genetic regulatory networks.

  3. Optimizing Transmission Network Expansion Planning With The Mean Of Chaotic Differential Evolution Algorithm

    Directory of Open Access Journals (Sweden)

    Ahmed R. Abdelaziz

    2015-08-01

    Full Text Available This paper presents an application of Chaotic differential evolution optimization approach meta-heuristics in solving transmission network expansion planning TNEP using an AC model associated with reactive power planning RPP. The reliabilityredundancy of network analysis optimization problems implicate selection of components with multiple choices and redundancy levels that produce maximum benefits can be subject to the cost weight and volume constraints is presented in this paper. Classical mathematical methods have failed in handling non-convexities and non-smoothness in optimization problems. As an alternative to the classical optimization approaches the meta-heuristics have attracted lot of attention due to their ability to find an almost global optimal solution in reliabilityredundancy optimization problems. Evolutionary algorithms EAs paradigms of evolutionary computation field are stochastic and robust meta-heuristics useful to solve reliabilityredundancy optimization problems. EAs such as genetic algorithm evolutionary programming evolution strategies and differential evolution are being used to find global or near global optimal solution. The Differential Evolution Algorithm DEA population-based algorithm is an optimal algorithm with powerful global searching capability but it is usually in low convergence speed and presents bad searching capability in the later evolution stage. A new Chaotic Differential Evolution algorithm CDE based on the cat map is recommended which combines DE and chaotic searching algorithm. Simulation results and comparisons show that the chaotic differential evolution algorithm using Cat map is competitive and stable in performance with other optimization approaches and other maps.

  4. Evolution of Cooperation in Social Dilemmas on Complex Networks

    Science.gov (United States)

    Iyer, Swami; Killingback, Timothy

    2016-01-01

    Cooperation in social dilemmas is essential for the functioning of systems at multiple levels of complexity, from the simplest biological organisms to the most sophisticated human societies. Cooperation, although widespread, is fundamentally challenging to explain evolutionarily, since natural selection typically favors selfish behavior which is not socially optimal. Here we study the evolution of cooperation in three exemplars of key social dilemmas, representing the prisoner’s dilemma, hawk-dove and coordination classes of games, in structured populations defined by complex networks. Using individual-based simulations of the games on model and empirical networks, we give a detailed comparative study of the effects of the structural properties of a network, such as its average degree, variance in degree distribution, clustering coefficient, and assortativity coefficient, on the promotion of cooperative behavior in all three classes of games. PMID:26928428

  5. Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling

    Science.gov (United States)

    Shin, Young Shik; Remacle, F.; Fan, Rong; Hwang, Kiwook; Wei, Wei; Ahmad, Habib; Levine, R.D.; Heath, James R.

    2011-01-01

    Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,···), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network. PMID:21575571

  6. On cooperative and efficient overlay network evolution based on a group selection pattern.

    Science.gov (United States)

    Nakao, Akihiro; Wang, Yufeng

    2010-04-01

    In overlay networks, the interplay between network structure and dynamics remains largely unexplored. In this paper, we study dynamic coevolution between individual rational strategies (cooperative or defect) and the overlay network structure, that is, the interaction between peer's local rational behaviors and the emergence of the whole network structure. We propose an evolutionary game theory (EGT)-based overlay topology evolution scheme to drive a given overlay into the small-world structure (high global network efficiency and average clustering coefficient). Our contributions are the following threefold: From the viewpoint of peers' local interactions, we explicitly consider the peer's rational behavior and introduce a link-formation game to characterize the social dilemma of forming links in an overlay network. Furthermore, in the evolutionary link-formation phase, we adopt a simple economic process: Each peer keeps one link to a cooperative neighbor in its neighborhood, which can slightly speed up the convergence of cooperation and increase network efficiency; from the viewpoint of the whole network structure, our simulation results show that the EGT-based scheme can drive an arbitrary overlay network into a fully cooperative and efficient small-world structure. Moreover, we compare our scheme with a search-based economic model of network formation and illustrate that our scheme can achieve the experimental and analytical results in the latter model. In addition, we also graphically illustrate the final overlay network structure; finally, based on the group selection model and evolutionary set theory, we theoretically obtain the approximate threshold of cost and draw the conclusion that the small value of the average degree and the large number of the total peers in an overlay network facilitate the evolution of cooperation.

  7. Genes2Networks: connecting lists of gene symbols using mammalian protein interactions databases

    Directory of Open Access Journals (Sweden)

    Ma'ayan Avi

    2007-10-01

    Full Text Available Abstract Background In recent years, mammalian protein-protein interaction network databases have been developed. The interactions in these databases are either extracted manually from low-throughput experimental biomedical research literature, extracted automatically from literature using techniques such as natural language processing (NLP, generated experimentally using high-throughput methods such as yeast-2-hybrid screens, or interactions are predicted using an assortment of computational approaches. Genes or proteins identified as significantly changing in proteomic experiments, or identified as susceptibility disease genes in genomic studies, can be placed in the context of protein interaction networks in order to assign these genes and proteins to pathways and protein complexes. Results Genes2Networks is a software system that integrates the content of ten mammalian interaction network datasets. Filtering techniques to prune low-confidence interactions were implemented. Genes2Networks is delivered as a web-based service using AJAX. The system can be used to extract relevant subnetworks created from "seed" lists of human Entrez gene symbols. The output includes a dynamic linkable three color web-based network map, with a statistical analysis report that identifies significant intermediate nodes used to connect the seed list. Conclusion Genes2Networks is powerful web-based software that can help experimental biologists to interpret lists of genes and proteins such as those commonly produced through genomic and proteomic experiments, as well as lists of genes and proteins associated with disease processes. This system can be used to find relationships between genes and proteins from seed lists, and predict additional genes or proteins that may play key roles in common pathways or protein complexes.

  8. Interrogating the architecture of protein assemblies and protein interaction networks by cross-linking mass spectrometry

    NARCIS (Netherlands)

    Liu, Fan; Heck, Albert J R

    2015-01-01

    Proteins are involved in almost all processes of the living cell. They are organized through extensive networks of interaction, by tightly bound macromolecular assemblies or more transiently via signaling nodes. Therefore, revealing the architecture of protein complexes and protein interaction

  9. Comparative empirical analysis of flow-weighted transit route networks in R-space and evolution modeling

    Science.gov (United States)

    Huang, Ailing; Zang, Guangzhi; He, Zhengbing; Guan, Wei

    2017-05-01

    Urban public transit system is a typical mixed complex network with dynamic flow, and its evolution should be a process coupling topological structure with flow dynamics, which has received little attention. This paper presents the R-space to make a comparative empirical analysis on Beijing’s flow-weighted transit route network (TRN) and we found that both the Beijing’s TRNs in the year of 2011 and 2015 exhibit the scale-free properties. As such, we propose an evolution model driven by flow to simulate the development of TRNs with consideration of the passengers’ dynamical behaviors triggered by topological change. The model simulates that the evolution of TRN is an iterative process. At each time step, a certain number of new routes are generated driven by travel demands, which leads to dynamical evolution of new routes’ flow and triggers perturbation in nearby routes that will further impact the next round of opening new routes. We present the theoretical analysis based on the mean-field theory, as well as the numerical simulation for this model. The results obtained agree well with our empirical analysis results, which indicate that our model can simulate the TRN evolution with scale-free properties for distributions of node’s strength and degree. The purpose of this paper is to illustrate the global evolutional mechanism of transit network that will be used to exploit planning and design strategies for real TRNs.

  10. Peptide microarrays to probe for competition for binding sites in a protein interaction network

    NARCIS (Netherlands)

    Sinzinger, M.D.S.; Ruttekolk, I.R.R.; Gloerich, J.; Wessels, H.; Chung, Y.D.; Adjobo-Hermans, M.J.W.; Brock, R.E.

    2013-01-01

    Cellular protein interaction networks are a result of the binding preferences of a particular protein and the entirety of interactors that mutually compete for binding sites. Therefore, the reconstruction of interaction networks by the accumulation of interaction networks for individual proteins

  11. The DIMA web resource--exploring the protein domain network.

    Science.gov (United States)

    Pagel, Philipp; Oesterheld, Matthias; Stümpflen, Volker; Frishman, Dmitrij

    2006-04-15

    Conserved domains represent essential building blocks of most known proteins. Owing to their role as modular components carrying out specific functions they form a network based both on functional relations and direct physical interactions. We have previously shown that domain interaction networks provide substantially novel information with respect to networks built on full-length protein chains. In this work we present a comprehensive web resource for exploring the Domain Interaction MAp (DIMA), interactively. The tool aims at integration of multiple data sources and prediction techniques, two of which have been implemented so far: domain phylogenetic profiling and experimentally demonstrated domain contacts from known three-dimensional structures. A powerful yet simple user interface enables the user to compute, visualize, navigate and download domain networks based on specific search criteria. http://mips.gsf.de/genre/proj/dima

  12. Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

    Science.gov (United States)

    Dong, Zheng; Zhou, Hongyu; Tao, Peng

    2018-02-01

    PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

  13. Molecular evolution of the Paramyxoviridae and Rhabdoviridae multiple-protein-encoding P gene.

    Science.gov (United States)

    Jordan, I K; Sutter, B A; McClure, M A

    2000-01-01

    Presented here is an analysis of the molecular evolutionary dynamics of the P gene among 76 representative sequences of the Paramyxoviridae and Rhabdoviridae RNA virus families. In a number of Paramyxoviridae taxa, as well as in vesicular stomatitis viruses of the Rhabdoviridae, the P gene encodes multiple proteins from a single genomic RNA sequence. These products include the phosphoprotein (P), as well as the C and V proteins. The complexity of the P gene makes it an intriguing locus to study from an evolutionary perspective. Amino acid sequence alignments of the proteins encoded at the P and N loci were used in independent phylogenetic reconstructions of the Paramyxoviridae and Rhabdoviridae families. P-gene-coding capacities were mapped onto the Paramyxoviridae phylogeny, and the most parsimonious path of multiple-coding-capacity evolution was determined. Levels of amino acid variation for Paramyxoviridae and Rhabdoviridae P-gene-encoded products were also analyzed. Proteins encoded in overlapping reading frames from the same nucleotides have different levels of amino acid variation. The nucleotide architecture that underlies the amino acid variation was determined in order to evaluate the role of selection in the evolution of the P gene overlapping reading frames. In every case, the evolution of one of the proteins encoded in the overlapping reading frames has been constrained by negative selection while the other has evolved more rapidly. The integrity of the overlapping reading frame that represents a derived state is generally maintained at the expense of the ancestral reading frame encoded by the same nucleotides. The evolution of such multicoding sequences is likely a response by RNA viruses to selective pressure to maximize genomic information content while maintaining small genome size. The ability to evolve such a complex genomic strategy is intimately related to the dynamics of the viral quasispecies, which allow enhanced exploration of the adaptive

  14. NASCENT: an automatic protein interaction network generation tool for non-model organisms.

    Science.gov (United States)

    Banky, Daniel; Ordog, Rafael; Grolmusz, Vince

    2009-04-24

    Large quantity of reliable protein interaction data are available for model organisms in public depositories (e.g., MINT, DIP, HPRD, INTERACT). Most data correspond to experiments with the proteins of Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Caenorhabditis elegans, Escherichia coli and Mus musculus. For other important organisms the data availability is poor or non-existent. Here we present NASCENT, a completely automatic web-based tool and also a downloadable Java program, capable of modeling and generating protein interaction networks even for non-model organisms. The tool performs protein interaction network modeling through gene-name mapping, and outputs the resulting network in graphical form and also in computer-readable graph-forms, directly applicable by popular network modeling software. http://nascent.pitgroup.org.

  15. Molecular evolution, intracellular organization, and the quinary structure of proteins.

    OpenAIRE

    McConkey, E H

    1982-01-01

    High-resolution two-dimensional polyacrylamide gel electrophoresis shows that at least half of 370 denatured polypeptides from hamster cells and human cells are indistinguishable in terms of isoelectric points and molecular weights. Molecular evolution may have been more conservative for this set of proteins than sequence studies on soluble proteins have implied. This may be a consequence of complexities of intracellular organization and the numerous macromolecular interactions in which most ...

  16. Birth and death of protein domains: A simple model of evolution explains power law behavior

    Directory of Open Access Journals (Sweden)

    Berezovskaya Faina S

    2002-10-01

    Full Text Available Abstract Background Power distributions appear in numerous biological, physical and other contexts, which appear to be fundamentally different. In biology, power laws have been claimed to describe the distributions of the connections of enzymes and metabolites in metabolic networks, the number of interactions partners of a given protein, the number of members in paralogous families, and other quantities. In network analysis, power laws imply evolution of the network with preferential attachment, i.e. a greater likelihood of nodes being added to pre-existing hubs. Exploration of different types of evolutionary models in an attempt to determine which of them lead to power law distributions has the potential of revealing non-trivial aspects of genome evolution. Results A simple model of evolution of the domain composition of proteomes was developed, with the following elementary processes: i domain birth (duplication with divergence, ii death (inactivation and/or deletion, and iii innovation (emergence from non-coding or non-globular sequences or acquisition via horizontal gene transfer. This formalism can be described as a birth, death and innovation model (BDIM. The formulas for equilibrium frequencies of domain families of different size and the total number of families at equilibrium are derived for a general BDIM. All asymptotics of equilibrium frequencies of domain families possible for the given type of models are found and their appearance depending on model parameters is investigated. It is proved that the power law asymptotics appears if, and only if, the model is balanced, i.e. domain duplication and deletion rates are asymptotically equal up to the second order. It is further proved that any power asymptotic with the degree not equal to -1 can appear only if the hypothesis of independence of the duplication/deletion rates on the size of a domain family is rejected. Specific cases of BDIMs, namely simple, linear, polynomial and rational

  17. Reassessing Domain Architecture Evolution of Metazoan Proteins: The Contribution of Different Evolutionary Mechanisms

    Directory of Open Access Journals (Sweden)

    Laszlo Patthy

    2011-08-01

    Full Text Available In the accompanying papers we have shown that sequence errors of public databases and confusion of paralogs and epaktologs (proteins that are related only through the independent acquisition of the same domain types significantly distort the picture that emerges from comparison of the domain architecture (DA of multidomain Metazoan proteins since they introduce a strong bias in favor of terminal over internal DA change. The issue of whether terminal or internal DA changes occur with greater probability has very important implications for the DA evolution of multidomain proteins since gene fusion can add domains only at terminal positions, whereas domain-shuffling is capable of inserting domains both at internal and terminal positions. As a corollary, overestimation of terminal DA changes may be misinterpreted as evidence for a dominant role of gene fusion in DA evolution. In this manuscript we show that in several recent studies of DA evolution of Metazoa the authors used databases that are significantly contaminated with incomplete, abnormal and mispredicted sequences (e.g., UniProtKB/TrEMBL, EnsEMBL and/or the authors failed to separate paralogs and epaktologs, explaining why these studies concluded that the major mechanism for gains of new domains in metazoan proteins is gene fusion. In contrast with the latter conclusion, our studies on high quality orthologous and paralogous Swiss-Prot sequences confirm that shuffling of mobile domains had a major role in the evolution of multidomain proteins of Metazoa and especially those formed in early vertebrates.

  18. Randomly biased investments and the evolution of public goods on interdependent networks

    Science.gov (United States)

    Chen, Wei; Wu, Te; Li, Zhiwu; Wang, Long

    2017-08-01

    Deciding how to allocate resources between interdependent systems is significant to optimize efficiency. We study the effects of heterogeneous contribution, induced by such interdependency, on the evolution of cooperation, through implementing the public goods games on two-layer networks. The corresponding players on different layers try to share a fixed amount of resources as the initial investment properly. The symmetry breaking of investments between players located on different layers is able to either prevent investments from, or extract them out of the deadlock. Results show that a moderate investment heterogeneity is best favorable for the evolution of cooperation, and random allocation of investment bias suppresses the cooperators at a wide range of the investment bias and the enhancement effect. Further studies on time evolution with different initial strategy configurations show that the non-interdependent cooperators along the interface of interdependent cooperators also are an indispensable factor in facilitating cooperative behavior. Our main results are qualitatively unchanged even diversifying investment bias that is subject to uniform distribution. Our study may shed light on the understanding of the origin of cooperative behavior on interdependent networks.

  19. Minimum curvilinearity to enhance topological prediction of protein interactions by network embedding

    KAUST Repository

    Cannistraci, Carlo

    2013-06-21

    Motivation: Most functions within the cell emerge thanks to protein-protein interactions (PPIs), yet experimental determination of PPIs is both expensive and time-consuming. PPI networks present significant levels of noise and incompleteness. Predicting interactions using only PPI-network topology (topological prediction) is difficult but essential when prior biological knowledge is absent or unreliable.Methods: Network embedding emphasizes the relations between network proteins embedded in a low-dimensional space, in which protein pairs that are closer to each other represent good candidate interactions. To achieve network denoising, which boosts prediction performance, we first applied minimum curvilinear embedding (MCE), and then adopted shortest path (SP) in the reduced space to assign likelihood scores to candidate interactions. Furthermore, we introduce (i) a new valid variation of MCE, named non-centred MCE (ncMCE); (ii) two automatic strategies for selecting the appropriate embedding dimension; and (iii) two new randomized procedures for evaluating predictions.Results: We compared our method against several unsupervised and supervisedly tuned embedding approaches and node neighbourhood techniques. Despite its computational simplicity, ncMCE-SP was the overall leader, outperforming the current methods in topological link prediction.Conclusion: Minimum curvilinearity is a valuable non-linear framework that we successfully applied to the embedding of protein networks for the unsupervised prediction of novel PPIs. The rationale for our approach is that biological and evolutionary information is imprinted in the non-linear patterns hidden behind the protein network topology, and can be exploited for predicting new protein links. The predicted PPIs represent good candidates for testing in high-throughput experiments or for exploitation in systems biology tools such as those used for network-based inference and prediction of disease-related functional modules. The

  20. Cytoprophet: a Cytoscape plug-in for protein and domain interaction networks inference.

    Science.gov (United States)

    Morcos, Faruck; Lamanna, Charles; Sikora, Marcin; Izaguirre, Jesús

    2008-10-01

    Cytoprophet is a software tool that allows prediction and visualization of protein and domain interaction networks. It is implemented as a plug-in of Cytoscape, an open source software framework for analysis and visualization of molecular networks. Cytoprophet implements three algorithms that predict new potential physical interactions using the domain composition of proteins and experimental assays. The algorithms for protein and domain interaction inference include maximum likelihood estimation (MLE) using expectation maximization (EM); the set cover approach maximum specificity set cover (MSSC) and the sum-product algorithm (SPA). After accepting an input set of proteins with Uniprot ID/Accession numbers and a selected prediction algorithm, Cytoprophet draws a network of potential interactions with probability scores and GO distances as edge attributes. A network of domain interactions between the domains of the initial protein list can also be generated. Cytoprophet was designed to take advantage of the visual capabilities of Cytoscape and be simple to use. An example of inference in a signaling network of myxobacterium Myxococcus xanthus is presented and available at Cytoprophet's website. http://cytoprophet.cse.nd.edu.

  1. Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs

    Directory of Open Access Journals (Sweden)

    David Juan

    2016-02-01

    Full Text Available Summary: Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC co-localizes with specific interactors shows that each interaction points to chromatin remodeling, stemness, differentiation, or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs. : 5-hydroxymethylcytosine (5hmC plays a key role in the epigenomic communication network of embryonic stem cells. Juan et al. build a communication network based in co-localization of epigenomic data and literature. The analysis of the network and its components reveals that proteins reading and editing 5hmC co-evolve and serve as links between diverse molecular processes.

  2. Evolution-development congruence in pattern formation dynamics: Bifurcations in gene expression and regulation of networks structures.

    Science.gov (United States)

    Kohsokabe, Takahiro; Kaneko, Kunihiko

    2016-01-01

    Search for possible relationships between phylogeny and ontogeny is important in evolutionary-developmental biology. Here we uncover such relationships by numerical evolution and unveil their origin in terms of dynamical systems theory. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell-to-cell interaction under external morphogen gradient, gene regulation networks are evolved under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Both in the evolution and development pattern changes consist of several epochs where stripes are formed in a short time, while for other temporal regimes, pattern hardly changes. In evolution, these quasi-stationary regimes are generations needed to hit relevant mutations, while in development, they are due to some gene expression that varies slowly and controls the pattern change. The morphogenesis is regulated by combinations of feedback or feedforward regulations, where the upstream feedforward network reads the external morphogen gradient, and generates a pattern used as a boundary condition for the later patterns. The ordering from up to downstream is common in evolution and development, while the successive epochal changes in development and evolution are represented as common bifurcations in dynamical-systems theory, which lead to the evolution-development congruence. Mechanism of exceptional violation of the congruence is also unveiled. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution Published by Wiley Periodicals, Inc.

  3. Network evolution induced by the dynamical rules of two populations

    International Nuclear Information System (INIS)

    Platini, Thierry; Zia, R K P

    2010-01-01

    We study the dynamical properties of a finite dynamical network composed of two interacting populations, namely extrovert (a) and introvert (b). In our model, each group is characterized by its size (N a and N b ) and preferred degree (κ a and κ b a ). The network dynamics is governed by the competing microscopic rules of each population that consist of the creation and destruction of links. Starting from an unconnected network, we give a detailed analysis of the mean field approach which is compared to Monte Carlo simulation data. The time evolution of the restricted degrees (k bb ) and (k ab ) presents three time regimes and a non-monotonic behavior well captured by our theory. Surprisingly, when the population sizes are equal N a = N b , the ratio of the restricted degree θ 0 = (k ab )/(k bb ) appears to be an integer in the asymptotic limits of the three time regimes. For early times (defined by t 1 = κ b ) the total number of links presents a linear evolution, where the two populations are indistinguishable and where θ 0 = 1. Interestingly, in the intermediate time regime (defined for t 1 2 ∝κ a and for which θ 0 = 5), the system reaches a transient stationary state, where the number of contacts among introverts remains constant while the number of connections increases linearly in the extrovert population. Finally, due to the competing dynamics, the network presents a frustrated stationary state characterized by a ratio θ 0 = 3

  4. Architecture and dynamics of overlapped RNA regulatory networks.

    Science.gov (United States)

    Lapointe, Christopher P; Preston, Melanie A; Wilinski, Daniel; Saunders, Harriet A J; Campbell, Zachary T; Wickens, Marvin

    2017-11-01

    A single protein can bind and regulate many mRNAs. Multiple proteins with similar specificities often bind and control overlapping sets of mRNAs. Yet little is known about the architecture or dynamics of overlapped networks. We focused on three proteins with similar structures and related RNA-binding specificities-Puf3p, Puf4p, and Puf5p of S. cerevisiae Using RNA Tagging, we identified a "super-network" comprised of four subnetworks: Puf3p, Puf4p, and Puf5p subnetworks, and one controlled by both Puf4p and Puf5p. The architecture of individual subnetworks, and thus the super-network, is determined by competition among particular PUF proteins to bind mRNAs, their affinities for binding elements, and the abundances of the proteins. The super-network responds dramatically: The remaining network can either expand or contract. These strikingly opposite outcomes are determined by an interplay between the relative abundance of the RNAs and proteins, and their affinities for one another. The diverse interplay between overlapping RNA-protein networks provides versatile opportunities for regulation and evolution. © 2017 Lapointe et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  5. Protein complex detection in PPI networks based on data integration and supervised learning method.

    Science.gov (United States)

    Yu, Feng; Yang, Zhi; Hu, Xiao; Sun, Yuan; Lin, Hong; Wang, Jian

    2015-01-01

    Revealing protein complexes are important for understanding principles of cellular organization and function. High-throughput experimental techniques have produced a large amount of protein interactions, which makes it possible to predict protein complexes from protein-protein interaction (PPI) networks. However, the small amount of known physical interactions may limit protein complex detection. The new PPI networks are constructed by integrating PPI datasets with the large and readily available PPI data from biomedical literature, and then the less reliable PPI between two proteins are filtered out based on semantic similarity and topological similarity of the two proteins. Finally, the supervised learning protein complex detection (SLPC), which can make full use of the information of available known complexes, is applied to detect protein complex on the new PPI networks. The experimental results of SLPC on two different categories yeast PPI networks demonstrate effectiveness of the approach: compared with the original PPI networks, the best average improvements of 4.76, 6.81 and 15.75 percentage units in the F-score, accuracy and maximum matching ratio (MMR) are achieved respectively; compared with the denoising PPI networks, the best average improvements of 3.91, 4.61 and 12.10 percentage units in the F-score, accuracy and MMR are achieved respectively; compared with ClusterONE, the start-of the-art complex detection method, on the denoising extended PPI networks, the average improvements of 26.02 and 22.40 percentage units in the F-score and MMR are achieved respectively. The experimental results show that the performances of SLPC have a large improvement through integration of new receivable PPI data from biomedical literature into original PPI networks and denoising PPI networks. In addition, our protein complexes detection method can achieve better performance than ClusterONE.

  6. Gains of ubiquitylation sites in highly conserved proteins in the human lineage

    Directory of Open Access Journals (Sweden)

    Kim Dong Seon

    2012-11-01

    Full Text Available Abstract Background Post-translational modification of lysine residues of specific proteins by ubiquitin modulates the degradation, localization, and activity of these target proteins. Here, we identified gains of ubiquitylation sites in highly conserved regions of human proteins that occurred during human evolution. Results We analyzed human ubiquitylation site data and multiple alignments of orthologous mammalian proteins including those from humans, primates, other placental mammals, opossum, and platypus. In our analysis, we identified 281 ubiquitylation sites in 252 proteins that first appeared along the human lineage during primate evolution: one protein had four novel sites; four proteins had three sites each; 18 proteins had two sites each; and the remaining 229 proteins had one site each. PML, which is involved in neurodevelopment and neurodegeneration, acquired three sites, two of which have been reported to be involved in the degradation of PML. Thirteen human proteins, including ERCC2 (also known as XPD and NBR1, gained human-specific ubiquitylated lysines after the human-chimpanzee divergence. ERCC2 has a Lys/Gln polymorphism, the derived (major allele of which confers enhanced DNA repair capacity and reduced cancer risk compared with the ancestral (minor allele. NBR1 and eight other proteins that are involved in the human autophagy protein interaction network gained a novel ubiquitylation site. Conclusions The gain of novel ubiquitylation sites could be involved in the evolution of protein degradation and other regulatory networks. Although gains of ubiquitylation sites do not necessarily equate to adaptive evolution, they are useful candidates for molecular functional analyses to identify novel advantageous genetic modifications and innovative phenotypes acquired during human evolution.

  7. Defining the protein interaction network of human malaria parasite Plasmodium falciparum

    KAUST Repository

    Ramaprasad, Abhinay

    2012-02-01

    Malaria, caused by the protozoan parasite Plasmodium falciparum, affects around 225. million people yearly and a huge international effort is directed towards combating this grave threat to world health and economic development. Considerable advances have been made in malaria research triggered by the sequencing of its genome in 2002, followed by several high-throughput studies defining the malaria transcriptome and proteome. A protein-protein interaction (PPI) network seeks to trace the dynamic interactions between proteins, thereby elucidating their local and global functional relationships. Experimentally derived PPI network from high-throughput methods such as yeast two hybrid (Y2H) screens are inherently noisy, but combining these independent datasets by computational methods tends to give a greater accuracy and coverage. This review aims to discuss the computational approaches used till date to construct a malaria protein interaction network and to catalog the functional predictions and biological inferences made from analysis of the PPI network. © 2011 Elsevier Inc.

  8. Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein.

    Directory of Open Access Journals (Sweden)

    Aditi Gupta

    2016-03-01

    Full Text Available Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It has been shown that strong selection increases epistatic interactions as well as the ruggedness of the fitness landscape, but little is known about how the epistatic interactions change under selection in the long-term evolution of a protein. Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1 using protease sequences collected for almost a decade from both treated and untreated patients, to understand how epistasis changes and how those changes impact the long-term evolvability of a protein. We use an information-theoretic proxy for epistasis that quantifies the co-variation between sites, and show that positive information is a necessary (but not sufficient condition that detects epistasis in most cases. We analyze the "fossils" of the evolutionary trajectories of the protein contained in the sequence data, and show that epistasis continues to enrich under strong selection, but not for proteins whose environment is unchanged. The increase in epistasis compensates for the information loss due to sequence variability brought about by treatment, and facilitates adaptation in the increasingly rugged fitness landscape of treatment. While epistasis is thought to enhance evolvability via valley-crossing early-on in adaptation, it can hinder adaptation later when the landscape has turned rugged. However, we find no evidence that the HIV-1 protease has reached its potential for evolution after 9 years of adapting to a drug environment that itself is constantly changing. We suggest that the mechanism of encoding new information into pairwise interactions is central to protein evolution not just in HIV-1 protease, but for any protein adapting to a changing

  9. TARSyn: Tunable Antibiotic Resistance Devices Enabling Bacterial Synthetic Evolution and Protein Production

    DEFF Research Database (Denmark)

    Rennig, Maja; Martinez, Virginia; Mirzadeh, Kiavash

    2018-01-01

    Evolution can be harnessed to optimize synthetic biology designs. A prominent example is recombinant protein production-a dominating theme in biotechnology for more than three decades. Typically, a protein coding sequence (cds) is recombined with genetic elements, such as promoters, ribosome...... and allows expression levels in large clone libraries to be probed using a simple cell survival assay on the respective antibiotic. The power of the approach is demonstrated by substantially increasing production of two commercially interesting proteins, a Nanobody and an Affibody. The method is a simple......-level expression-an example of synthetic evolution. However, manual screening limits the ability to assay expression levels of all putative sequences in the libraries. Here we have solved this bottleneck by designing a collection of translational coupling devices based on a RNA secondary structure. Exchange...

  10. PROFEAT Update: A Protein Features Web Server with Added Facility to Compute Network Descriptors for Studying Omics-Derived Networks.

    Science.gov (United States)

    Zhang, P; Tao, L; Zeng, X; Qin, C; Chen, S Y; Zhu, F; Yang, S Y; Li, Z R; Chen, W P; Chen, Y Z

    2017-02-03

    The studies of biological, disease, and pharmacological networks are facilitated by the systems-level investigations using computational tools. In particular, the network descriptors developed in other disciplines have found increasing applications in the study of the protein, gene regulatory, metabolic, disease, and drug-targeted networks. Facilities are provided by the public web servers for computing network descriptors, but many descriptors are not covered, including those used or useful for biological studies. We upgraded the PROFEAT web server http://bidd2.nus.edu.sg/cgi-bin/profeat2016/main.cgi for computing up to 329 network descriptors and protein-protein interaction descriptors. PROFEAT network descriptors comprehensively describe the topological and connectivity characteristics of unweighted (uniform binding constants and molecular levels), edge-weighted (varying binding constants), node-weighted (varying molecular levels), edge-node-weighted (varying binding constants and molecular levels), and directed (oriented processes) networks. The usefulness of the network descriptors is illustrated by the literature-reported studies of the biological networks derived from the genome, interactome, transcriptome, metabolome, and diseasome profiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Droplet networks with incorporated protein diodes show collective properties

    Science.gov (United States)

    Maglia, Giovanni; Heron, Andrew J.; Hwang, William L.; Holden, Matthew A.; Mikhailova, Ellina; Li, Qiuhong; Cheley, Stephen; Bayley, Hagan

    2009-07-01

    Recently, we demonstrated that submicrolitre aqueous droplets submerged in an apolar liquid containing lipid can be tightly connected by means of lipid bilayers to form networks. Droplet interface bilayers have been used for rapid screening of membrane proteins and to form asymmetric bilayers with which to examine the fundamental properties of channels and pores. Networks, meanwhile, have been used to form microscale batteries and to detect light. Here, we develop an engineered protein pore with diode-like properties that can be incorporated into droplet interface bilayers in droplet networks to form devices with electrical properties including those of a current limiter, a half-wave rectifier and a full-wave rectifier. The droplet approach, which uses unsophisticated components (oil, lipid, salt water and a simple pore), can therefore be used to create multidroplet networks with collective properties that cannot be produced by droplet pairs.

  12. Experimental and computational analysis of a large protein network that controls fat storage reveals the design principles of a signaling network.

    Science.gov (United States)

    Al-Anzi, Bader; Arpp, Patrick; Gerges, Sherif; Ormerod, Christopher; Olsman, Noah; Zinn, Kai

    2015-05-01

    An approach combining genetic, proteomic, computational, and physiological analysis was used to define a protein network that regulates fat storage in budding yeast (Saccharomyces cerevisiae). A computational analysis of this network shows that it is not scale-free, and is best approximated by the Watts-Strogatz model, which generates "small-world" networks with high clustering and short path lengths. The network is also modular, containing energy level sensing proteins that connect to four output processes: autophagy, fatty acid synthesis, mRNA processing, and MAP kinase signaling. The importance of each protein to network function is dependent on its Katz centrality score, which is related both to the protein's position within a module and to the module's relationship to the network as a whole. The network is also divisible into subnetworks that span modular boundaries and regulate different aspects of fat metabolism. We used a combination of genetics and pharmacology to simultaneously block output from multiple network nodes. The phenotypic results of this blockage define patterns of communication among distant network nodes, and these patterns are consistent with the Watts-Strogatz model.

  13. Unravelling Protein-Protein Interaction Networks Linked to Aliphatic and Indole Glucosinolate Biosynthetic Pathways in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Sebastian J. Nintemann

    2017-11-01

    Full Text Available Within the cell, biosynthetic pathways are embedded in protein-protein interaction networks. In Arabidopsis, the biosynthetic pathways of aliphatic and indole glucosinolate defense compounds are well-characterized. However, little is known about the spatial orchestration of these enzymes and their interplay with the cellular environment. To address these aspects, we applied two complementary, untargeted approaches—split-ubiquitin yeast 2-hybrid and co-immunoprecipitation screens—to identify proteins interacting with CYP83A1 and CYP83B1, two homologous enzymes specific for aliphatic and indole glucosinolate biosynthesis, respectively. Our analyses reveal distinct functional networks with substantial interconnection among the identified interactors for both pathway-specific markers, and add to our knowledge about how biochemical pathways are connected to cellular processes. Specifically, a group of protein interactors involved in cell death and the hypersensitive response provides a potential link between the glucosinolate defense compounds and defense against biotrophic pathogens, mediated by protein-protein interactions.

  14. Incorporating information on predicted solvent accessibility to the co-evolution-based study of protein interactions.

    Science.gov (United States)

    Ochoa, David; García-Gutiérrez, Ponciano; Juan, David; Valencia, Alfonso; Pazos, Florencio

    2013-01-27

    A widespread family of methods for studying and predicting protein interactions using sequence information is based on co-evolution, quantified as similarity of phylogenetic trees. Part of the co-evolution observed between interacting proteins could be due to co-adaptation caused by inter-protein contacts. In this case, the co-evolution is expected to be more evident when evaluated on the surface of the proteins or the internal layers close to it. In this work we study the effect of incorporating information on predicted solvent accessibility to three methods for predicting protein interactions based on similarity of phylogenetic trees. We evaluate the performance of these methods in predicting different types of protein associations when trees based on positions with different characteristics of predicted accessibility are used as input. We found that predicted accessibility improves the results of two recent versions of the mirrortree methodology in predicting direct binary physical interactions, while it neither improves these methods, nor the original mirrortree method, in predicting other types of interactions. That improvement comes at no cost in terms of applicability since accessibility can be predicted for any sequence. We also found that predictions of protein-protein interactions are improved when multiple sequence alignments with a richer representation of sequences (including paralogs) are incorporated in the accessibility prediction.

  15. Spectral properties of the temporal evolution of brain network structure.

    Science.gov (United States)

    Wang, Rong; Zhang, Zhen-Zhen; Ma, Jun; Yang, Yong; Lin, Pan; Wu, Ying

    2015-12-01

    The temporal evolution properties of the brain network are crucial for complex brain processes. In this paper, we investigate the differences in the dynamic brain network during resting and visual stimulation states in a task-positive subnetwork, task-negative subnetwork, and whole-brain network. The dynamic brain network is first constructed from human functional magnetic resonance imaging data based on the sliding window method, and then the eigenvalues corresponding to the network are calculated. We use eigenvalue analysis to analyze the global properties of eigenvalues and the random matrix theory (RMT) method to measure the local properties. For global properties, the shifting of the eigenvalue distribution and the decrease in the largest eigenvalue are linked to visual stimulation in all networks. For local properties, the short-range correlation in eigenvalues as measured by the nearest neighbor spacing distribution is not always sensitive to visual stimulation. However, the long-range correlation in eigenvalues as evaluated by spectral rigidity and number variance not only predicts the universal behavior of the dynamic brain network but also suggests non-consistent changes in different networks. These results demonstrate that the dynamic brain network is more random for the task-positive subnetwork and whole-brain network under visual stimulation but is more regular for the task-negative subnetwork. Our findings provide deeper insight into the importance of spectral properties in the functional brain network, especially the incomparable role of RMT in revealing the intrinsic properties of complex systems.

  16. Rapid directed evolution of stabilized proteins with cellular high-throughput encapsulation solubilization and screening (CHESS).

    Science.gov (United States)

    Yong, K J; Scott, D J

    2015-03-01

    Directed evolution is a powerful method for engineering proteins towards user-defined goals and has been used to generate novel proteins for industrial processes, biological research and drug discovery. Typical directed evolution techniques include cellular display, phage display, ribosome display and water-in-oil compartmentalization, all of which physically link individual members of diverse gene libraries to their translated proteins. This allows the screening or selection for a desired protein function and subsequent isolation of the encoding gene from diverse populations. For biotechnological and industrial applications there is a need to engineer proteins that are functional under conditions that are not compatible with these techniques, such as high temperatures and harsh detergents. Cellular High-throughput Encapsulation Solubilization and Screening (CHESS), is a directed evolution method originally developed to engineer detergent-stable G proteins-coupled receptors (GPCRs) for structural biology. With CHESS, library-transformed bacterial cells are encapsulated in detergent-resistant polymers to form capsules, which serve to contain mutant genes and their encoded proteins upon detergent mediated solubilization of cell membranes. Populations of capsules can be screened like single cells to enable rapid isolation of genes encoding detergent-stable protein mutants. To demonstrate the general applicability of CHESS to other proteins, we have characterized the stability and permeability of CHESS microcapsules and employed CHESS to generate thermostable, sodium dodecyl sulfate (SDS) resistant green fluorescent protein (GFP) mutants, the first soluble proteins to be engineered using CHESS. © 2014 Wiley Periodicals, Inc.

  17. Structure versus time in the evolutionary diversification of avian carotenoid metabolic networks.

    Science.gov (United States)

    Morrison, Erin S; Badyaev, Alexander V

    2018-05-01

    Historical associations of genes and proteins are thought to delineate pathways available to subsequent evolution; however, the effects of past functional involvements on contemporary evolution are rarely quantified. Here, we examined the extent to which the structure of a carotenoid enzymatic network persists in avian evolution. Specifically, we tested whether the evolution of carotenoid networks was most concordant with phylogenetically structured expansion from core reactions of common ancestors or with subsampling of biochemical pathway modules from an ancestral network. We compared structural and historical associations in 467 carotenoid networks of extant and ancestral species and uncovered the overwhelming effect of pre-existing metabolic network structure on carotenoid diversification over the last 50 million years of avian evolution. Over evolutionary time, birds repeatedly subsampled and recombined conserved biochemical modules, which likely maintained the overall structure of the carotenoid metabolic network during avian evolution. These findings explain the recurrent convergence of evolutionary distant species in carotenoid metabolism and weak phylogenetic signal in avian carotenoid evolution. Remarkable retention of an ancient metabolic structure throughout extensive and prolonged ecological diversification in avian carotenoid metabolism illustrates a fundamental requirement of organismal evolution - historical continuity of a deterministic network that links past and present functional associations of its components. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

  18. Molecular networks and the evolution of human cognitive specializations.

    Science.gov (United States)

    Fontenot, Miles; Konopka, Genevieve

    2014-12-01

    Inroads into elucidating the origins of human cognitive specializations have taken many forms, including genetic, genomic, anatomical, and behavioral assays that typically compare humans to non-human primates. While the integration of all of these approaches is essential for ultimately understanding human cognition, here, we review the usefulness of coexpression network analysis for specifically addressing this question. An increasing number of studies have incorporated coexpression networks into brain expression studies comparing species, disease versus control tissue, brain regions, or developmental time periods. A clearer picture has emerged of the key genes driving brain evolution, as well as the developmental and regional contributions of gene expression patterns important for normal brain development and those misregulated in cognitive diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Evolution of opinions on social networks in the presence of competing committed groups.

    Science.gov (United States)

    Xie, Jierui; Emenheiser, Jeffrey; Kirby, Matthew; Sreenivasan, Sameet; Szymanski, Boleslaw K; Korniss, Gyorgy

    2012-01-01

    Public opinion is often affected by the presence of committed groups of individuals dedicated to competing points of view. Using a model of pairwise social influence, we study how the presence of such groups within social networks affects the outcome and the speed of evolution of the overall opinion on the network. Earlier work indicated that a single committed group within a dense social network can cause the entire network to quickly adopt the group's opinion (in times scaling logarithmically with the network size), so long as the committed group constitutes more than about 10% of the population (with the findings being qualitatively similar for sparse networks as well). Here we study the more general case of opinion evolution when two groups committed to distinct, competing opinions A and B, and constituting fractions pA and pB of the total population respectively, are present in the network. We show for stylized social networks (including Erdös-Rényi random graphs and Barabási-Albert scale-free networks) that the phase diagram of this system in parameter space (pA,pB) consists of two regions, one where two stable steady-states coexist, and the remaining where only a single stable steady-state exists. These two regions are separated by two fold-bifurcation (spinodal) lines which meet tangentially and terminate at a cusp (critical point). We provide further insights to the phase diagram and to the nature of the underlying phase transitions by investigating the model on infinite (mean-field limit), finite complete graphs and finite sparse networks. For the latter case, we also derive the scaling exponent associated with the exponential growth of switching times as a function of the distance from the critical point.

  20. Experimental and computational analysis of a large protein network that controls fat storage reveals the design principles of a signaling network.

    Directory of Open Access Journals (Sweden)

    Bader Al-Anzi

    2015-05-01

    Full Text Available An approach combining genetic, proteomic, computational, and physiological analysis was used to define a protein network that regulates fat storage in budding yeast (Saccharomyces cerevisiae. A computational analysis of this network shows that it is not scale-free, and is best approximated by the Watts-Strogatz model, which generates "small-world" networks with high clustering and short path lengths. The network is also modular, containing energy level sensing proteins that connect to four output processes: autophagy, fatty acid synthesis, mRNA processing, and MAP kinase signaling. The importance of each protein to network function is dependent on its Katz centrality score, which is related both to the protein's position within a module and to the module's relationship to the network as a whole. The network is also divisible into subnetworks that span modular boundaries and regulate different aspects of fat metabolism. We used a combination of genetics and pharmacology to simultaneously block output from multiple network nodes. The phenotypic results of this blockage define patterns of communication among distant network nodes, and these patterns are consistent with the Watts-Strogatz model.

  1. Protein consensus-based surface engineering (ProCoS): a computer-assisted method for directed protein evolution.

    Science.gov (United States)

    Shivange, Amol V; Hoeffken, Hans Wolfgang; Haefner, Stefan; Schwaneberg, Ulrich

    2016-12-01

    Protein consensus-based surface engineering (ProCoS) is a simple and efficient method for directed protein evolution combining computational analysis and molecular biology tools to engineer protein surfaces. ProCoS is based on the hypothesis that conserved residues originated from a common ancestor and that these residues are crucial for the function of a protein, whereas highly variable regions (situated on the surface of a protein) can be targeted for surface engineering to maximize performance. ProCoS comprises four main steps: ( i ) identification of conserved and highly variable regions; ( ii ) protein sequence design by substituting residues in the highly variable regions, and gene synthesis; ( iii ) in vitro DNA recombination of synthetic genes; and ( iv ) screening for active variants. ProCoS is a simple method for surface mutagenesis in which multiple sequence alignment is used for selection of surface residues based on a structural model. To demonstrate the technique's utility for directed evolution, the surface of a phytase enzyme from Yersinia mollaretii (Ymphytase) was subjected to ProCoS. Screening just 1050 clones from ProCoS engineering-guided mutant libraries yielded an enzyme with 34 amino acid substitutions. The surface-engineered Ymphytase exhibited 3.8-fold higher pH stability (at pH 2.8 for 3 h) and retained 40% of the enzyme's specific activity (400 U/mg) compared with the wild-type Ymphytase. The pH stability might be attributed to a significantly increased (20 percentage points; from 9% to 29%) number of negatively charged amino acids on the surface of the engineered phytase.

  2. A Bayesian Network Based Adaptability Design of Product Structures for Function Evolution

    Directory of Open Access Journals (Sweden)

    Shaobo Li

    2018-03-01

    Full Text Available Structure adaptability design is critical for function evolution in product families, in which many structural and functional design factors are intertwined together with manufacturing cost, customer satisfaction, and final market sales. How to achieve a delicate balance among all of these factors to maximize the market performance of the product is too complicated to address based on traditional domain experts’ knowledge or some ad hoc heuristics. Here, we propose a quantitative product evolution design model that is based on Bayesian networks to model the dynamic relationship between customer needs and product structure design. In our model, all of the structural or functional features along with customer satisfaction, manufacturing cost, sale price, market sales, and indirect factors are modeled as random variables denoted as nodes in the Bayesian networks. The structure of the Bayesian model is then determined based on the historical data, which captures the dynamic sophisticated relationship of customer demands of a product, structural design, and market performance. Application of our approach to an electric toothbrush product family evolution design problem shows that our model allows for designers to interrogate with the model and obtain theoretical and decision support for dynamic product feature design process.

  3. Exploring overlapping functional units with various structure in protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Xiao-Fei Zhang

    Full Text Available Revealing functional units in protein-protein interaction (PPI networks are important for understanding cellular functional organization. Current algorithms for identifying functional units mainly focus on cohesive protein complexes which have more internal interactions than external interactions. Most of these approaches do not handle overlaps among complexes since they usually allow a protein to belong to only one complex. Moreover, recent studies have shown that other non-cohesive structural functional units beyond complexes also exist in PPI networks. Thus previous algorithms that just focus on non-overlapping cohesive complexes are not able to present the biological reality fully. Here, we develop a new regularized sparse random graph model (RSRGM to explore overlapping and various structural functional units in PPI networks. RSRGM is principally dominated by two model parameters. One is used to define the functional units as groups of proteins that have similar patterns of connections to others, which allows RSRGM to detect non-cohesive structural functional units. The other one is used to represent the degree of proteins belonging to the units, which supports a protein belonging to more than one revealed unit. We also propose a regularizer to control the smoothness between the estimators of these two parameters. Experimental results on four S. cerevisiae PPI networks show that the performance of RSRGM on detecting cohesive complexes and overlapping complexes is superior to that of previous competing algorithms. Moreover, RSRGM has the ability to discover biological significant functional units besides complexes.

  4. Preferential attachment in the evolution of metabolic networks

    Directory of Open Access Journals (Sweden)

    Elofsson Arne

    2005-11-01

    Full Text Available Abstract Background Many biological networks show some characteristics of scale-free networks. Scale-free networks can evolve through preferential attachment where new nodes are preferentially attached to well connected nodes. In networks which have evolved through preferential attachment older nodes should have a higher average connectivity than younger nodes. Here we have investigated preferential attachment in the context of metabolic networks. Results The connectivities of the enzymes in the metabolic network of Escherichia coli were determined and representatives for these enzymes were located in 11 eukaryotes, 17 archaea and 46 bacteria. E. coli enzymes which have representatives in eukaryotes have a higher average connectivity while enzymes which are represented only in the prokaryotes, and especially the enzymes only present in βγ-proteobacteria, have lower connectivities than expected by chance. Interestingly, the enzymes which have been proposed as candidates for horizontal gene transfer have a higher average connectivity than the other enzymes. Furthermore, It was found that new edges are added to the highly connected enzymes at a faster rate than to enzymes with low connectivities which is consistent with preferential attachment. Conclusion Here, we have found indications of preferential attachment in the metabolic network of E. coli. A possible biological explanation for preferential attachment growth of metabolic networks is that novel enzymes created through gene duplication maintain some of the compounds involved in the original reaction, throughout its future evolution. In addition, we found that enzymes which are candidates for horizontal gene transfer have a higher average connectivity than other enzymes. This indicates that while new enzymes are attached preferentially to highly connected enzymes, these highly connected enzymes have sometimes been introduced into the E. coli genome by horizontal gene transfer. We speculate

  5. Evolution of light-harvesting complex proteins from Chl c-containing algae

    Directory of Open Access Journals (Sweden)

    Puerta M Virginia

    2011-04-01

    Full Text Available Abstract Background Light harvesting complex (LHC proteins function in photosynthesis by binding chlorophyll (Chl and carotenoid molecules that absorb light and transfer the energy to the reaction center Chl of the photosystem. Most research has focused on LHCs of plants and chlorophytes that bind Chl a and b and extensive work on these proteins has uncovered a diversity of biochemical functions, expression patterns and amino acid sequences. We focus here on a less-studied family of LHCs that typically bind Chl a and c, and that are widely distributed in Chl c-containing and other algae. Previous phylogenetic analyses of these proteins suggested that individual algal lineages possess proteins from one or two subfamilies, and that most subfamilies are characteristic of a particular algal lineage, but genome-scale datasets had revealed that some species have multiple different forms of the gene. Such observations also suggested that there might have been an important influence of endosymbiosis in the evolution of LHCs. Results We reconstruct a phylogeny of LHCs from Chl c-containing algae and related lineages using data from recent sequencing projects to give ~10-fold larger taxon sampling than previous studies. The phylogeny indicates that individual taxa possess proteins from multiple LHC subfamilies and that several LHC subfamilies are found in distantly related algal lineages. This phylogenetic pattern implies functional differentiation of the gene families, a hypothesis that is consistent with data on gene expression, carotenoid binding and physical associations with other LHCs. In all probability LHCs have undergone a complex history of evolution of function, gene transfer, and lineage-specific diversification. Conclusion The analysis provides a strikingly different picture of LHC diversity than previous analyses of LHC evolution. Individual algal lineages possess proteins from multiple LHC subfamilies. Evolutionary relationships showed

  6. Evolution of the large Deep Space Network antennas

    Science.gov (United States)

    Imbriale, William A.

    1991-12-01

    The evolution of the largest antenna of the US NASA Deep Space Network (DSN) is described. The design, performance analysis, and measurement techniques, beginning with its initial 64-m operation at S-band (2295 MHz) in 1966 and continuing through the present ka-band (32-GHz) operation at 70 m, is described. Although their diameters and mountings differ, these parabolic antennas all employ a Cassegrainian feed system, and each antenna dish surface is constructed of precision-shaped perforated-aluminum panels that are secured to an open steel framework

  7. Protein Secondary Structure Prediction Using AutoEncoder Network and Bayes Classifier

    Science.gov (United States)

    Wang, Leilei; Cheng, Jinyong

    2018-03-01

    Protein secondary structure prediction is belong to bioinformatics,and it's important in research area. In this paper, we propose a new prediction way of protein using bayes classifier and autoEncoder network. Our experiments show some algorithms including the construction of the model, the classification of parameters and so on. The data set is a typical CB513 data set for protein. In terms of accuracy, the method is the cross validation based on the 3-fold. Then we can get the Q3 accuracy. Paper results illustrate that the autoencoder network improved the prediction accuracy of protein secondary structure.

  8. Evolution of context dependent regulation by expansion of feast/famine regulatory proteins.

    Science.gov (United States)

    Plaisier, Christopher L; Lo, Fang-Yin; Ashworth, Justin; Brooks, Aaron N; Beer, Karlyn D; Kaur, Amardeep; Pan, Min; Reiss, David J; Facciotti, Marc T; Baliga, Nitin S

    2014-11-14

    Expansion of transcription factors is believed to have played a crucial role in evolution of all organisms by enabling them to deal with dynamic environments and colonize new environments. We investigated how the expansion of the Feast/Famine Regulatory Protein (FFRP) or Lrp-like proteins into an eight-member family in Halobacterium salinarum NRC-1 has aided in niche-adaptation of this archaeon to a complex and dynamically changing hypersaline environment. We mapped genome-wide binding locations for all eight FFRPs, investigated their preference for binding different effector molecules, and identified the contexts in which they act by analyzing transcriptional responses across 35 growth conditions that mimic different environmental and nutritional conditions this organism is likely to encounter in the wild. Integrative analysis of these data constructed an FFRP regulatory network with conditionally active states that reveal how interrelated variations in DNA-binding domains, effector-molecule preferences, and binding sites in target gene promoters have tuned the functions of each FFRP to the environments in which they act. We demonstrate how conditional regulation of similar genes by two FFRPs, AsnC (an activator) and VNG1237C (a repressor), have striking environment-specific fitness consequences for oxidative stress management and growth, respectively. This study provides a systems perspective into the evolutionary process by which gene duplication within a transcription factor family contributes to environment-specific adaptation of an organism.

  9. Integration of relational and hierarchical network information for protein function prediction

    Directory of Open Access Journals (Sweden)

    Jiang Xiaoyu

    2008-08-01

    Full Text Available Abstract Background In the current climate of high-throughput computational biology, the inference of a protein's function from related measurements, such as protein-protein interaction relations, has become a canonical task. Most existing technologies pursue this task as a classification problem, on a term-by-term basis, for each term in a database, such as the Gene Ontology (GO database, a popular rigorous vocabulary for biological functions. However, ontology structures are essentially hierarchies, with certain top to bottom annotation rules which protein function predictions should in principle follow. Currently, the most common approach to imposing these hierarchical constraints on network-based classifiers is through the use of transitive closure to predictions. Results We propose a probabilistic framework to integrate information in relational data, in the form of a protein-protein interaction network, and a hierarchically structured database of terms, in the form of the GO database, for the purpose of protein function prediction. At the heart of our framework is a factorization of local neighborhood information in the protein-protein interaction network across successive ancestral terms in the GO hierarchy. We introduce a classifier within this framework, with computationally efficient implementation, that produces GO-term predictions that naturally obey a hierarchical 'true-path' consistency from root to leaves, without the need for further post-processing. Conclusion A cross-validation study, using data from the yeast Saccharomyces cerevisiae, shows our method offers substantial improvements over both standard 'guilt-by-association' (i.e., Nearest-Neighbor and more refined Markov random field methods, whether in their original form or when post-processed to artificially impose 'true-path' consistency. Further analysis of the results indicates that these improvements are associated with increased predictive capabilities (i.e., increased

  10. Evolution of cooperation under social pressure in multiplex networks.

    Science.gov (United States)

    Pereda, María

    2016-09-01

    In this work, we aim to contribute to the understanding of human prosocial behavior by studying the influence that a particular form of social pressure, "being watched," has on the evolution of cooperative behavior. We study how cooperation emerges in multiplex complex topologies by analyzing a particular bidirectionally coupled dynamics on top of a two-layer multiplex network (duplex). The coupled dynamics appears between the prisoner's dilemma game in a network and a threshold cascade model in the other. The threshold model is intended to abstract the behavior of a network of vigilant nodes that impose the pressure of being observed altering hence the temptation to defect of the dilemma. Cooperation or defection in the game also affects the state of a node of being vigilant. We analyze these processes on different duplex networks structures and assess the influence of the topology, average degree and correlated multiplexity, on the outcome of cooperation. Interestingly, we find that the social pressure of vigilance may impact cooperation positively or negatively, depending on the duplex structure, specifically the degree correlations between layers is determinant. Our results give further quantitative insights in the promotion of cooperation under social pressure.

  11. Identifying essential proteins based on sub-network partition and prioritization by integrating subcellular localization information.

    Science.gov (United States)

    Li, Min; Li, Wenkai; Wu, Fang-Xiang; Pan, Yi; Wang, Jianxin

    2018-06-14

    Essential proteins are important participants in various life activities and play a vital role in the survival and reproduction of living organisms. Identification of essential proteins from protein-protein interaction (PPI) networks has great significance to facilitate the study of human complex diseases, the design of drugs and the development of bioinformatics and computational science. Studies have shown that highly connected proteins in a PPI network tend to be essential. A series of computational methods have been proposed to identify essential proteins by analyzing topological structures of PPI networks. However, the high noise in the PPI data can degrade the accuracy of essential protein prediction. Moreover, proteins must be located in the appropriate subcellular localization to perform their functions, and only when the proteins are located in the same subcellular localization, it is possible that they can interact with each other. In this paper, we propose a new network-based essential protein discovery method based on sub-network partition and prioritization by integrating subcellular localization information, named SPP. The proposed method SPP was tested on two different yeast PPI networks obtained from DIP database and BioGRID database. The experimental results show that SPP can effectively reduce the effect of false positives in PPI networks and predict essential proteins more accurately compared with other existing computational methods DC, BC, CC, SC, EC, IC, NC. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Hepatitis C Virus Protein Interaction Network Analysis Based on Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yuewen Han

    Full Text Available Epidemiological studies have validated the association between hepatitis C virus (HCV infection and hepatocellular carcinoma (HCC. An increasing number of studies show that protein-protein interactions (PPIs between HCV proteins and host proteins play a vital role in infection and mediate HCC progression. In this work, we collected all published interaction between HCV and human proteins, which include 455 unique human proteins participating in 524 HCV-human interactions. Then, we construct the HCV-human and HCV-HCC protein interaction networks, which display the biological knowledge regarding the mechanism of HCV pathogenesis, particularly with respect to pathogenesis of HCC. Through in-depth analysis of the HCV-HCC interaction network, we found that interactors are enriched in the JAK/STAT, p53, MAPK, TNF, Wnt, and cell cycle pathways. Using a random walk with restart algorithm, we predicted the importance of each protein in the HCV-HCC network and found that AKT1 may play a key role in the HCC progression. Moreover, we found that NS5A promotes HCC cells proliferation and metastasis by activating AKT/GSK3β/β-catenin pathway. This work provides a basis for a detailed map tracking new cellular interactions of HCV and identifying potential targets for HCV-related hepatocellular carcinoma treatment.

  13. LARGE-SCALE TOPOLOGICAL PROPERTIES OF MOLECULAR NETWORKS.

    Energy Technology Data Exchange (ETDEWEB)

    MASLOV,S.SNEPPEN,K.

    2003-11-17

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

  14. Automatic extraction of gene ontology annotation and its correlation with clusters in protein networks

    Directory of Open Access Journals (Sweden)

    Mazo Ilya

    2007-07-01

    Full Text Available Abstract Background Uncovering cellular roles of a protein is a task of tremendous importance and complexity that requires dedicated experimental work as well as often sophisticated data mining and processing tools. Protein functions, often referred to as its annotations, are believed to manifest themselves through topology of the networks of inter-proteins interactions. In particular, there is a growing body of evidence that proteins performing the same function are more likely to interact with each other than with proteins with other functions. However, since functional annotation and protein network topology are often studied separately, the direct relationship between them has not been comprehensively demonstrated. In addition to having the general biological significance, such demonstration would further validate the data extraction and processing methods used to compose protein annotation and protein-protein interactions datasets. Results We developed a method for automatic extraction of protein functional annotation from scientific text based on the Natural Language Processing (NLP technology. For the protein annotation extracted from the entire PubMed, we evaluated the precision and recall rates, and compared the performance of the automatic extraction technology to that of manual curation used in public Gene Ontology (GO annotation. In the second part of our presentation, we reported a large-scale investigation into the correspondence between communities in the literature-based protein networks and GO annotation groups of functionally related proteins. We found a comprehensive two-way match: proteins within biological annotation groups form significantly denser linked network clusters than expected by chance and, conversely, densely linked network communities exhibit a pronounced non-random overlap with GO groups. We also expanded the publicly available GO biological process annotation using the relations extracted by our NLP technology

  15. The evolution of your success lies at the centre of your co-authorship network.

    Directory of Open Access Journals (Sweden)

    Sandra Servia-Rodríguez

    Full Text Available Collaboration among scholars and institutions is progressively becoming essential to the success of research grant procurement and to allow the emergence and evolution of scientific disciplines. Our work focuses on analysing if the volume of collaborations of one author together with the relevance of his collaborators is somewhat related to his research performance over time. In order to prove this relation we collected the temporal distributions of scholars' publications and citations from the Google Scholar platform and the co-authorship network (of Computer Scientists underlying the well-known DBLP bibliographic database. By the application of time series clustering, social network analysis and non-parametric statistics, we observe that scholars with similar publications (citations patterns also tend to have a similar centrality in the co-authorship network. To our knowledge, this is the first work that considers success evolution with respect to co-authorship.

  16. Protein Inference from the Integration of Tandem MS Data and Interactome Networks.

    Science.gov (United States)

    Zhong, Jiancheng; Wang, Jianxing; Ding, Xiaojun; Zhang, Zhen; Li, Min; Wu, Fang-Xiang; Pan, Yi

    2017-01-01

    Since proteins are digested into a mixture of peptides in the preprocessing step of tandem mass spectrometry (MS), it is difficult to determine which specific protein a shared peptide belongs to. In recent studies, besides tandem MS data and peptide identification information, some other information is exploited to infer proteins. Different from the methods which first use only tandem MS data to infer proteins and then use network information to refine them, this study proposes a protein inference method named TMSIN, which uses interactome networks directly. As two interacting proteins should co-exist, it is reasonable to assume that if one of the interacting proteins is confidently inferred in a sample, its interacting partners should have a high probability in the same sample, too. Therefore, we can use the neighborhood information of a protein in an interactome network to adjust the probability that the shared peptide belongs to the protein. In TMSIN, a multi-weighted graph is constructed by incorporating the bipartite graph with interactome network information, where the bipartite graph is built with the peptide identification information. Based on multi-weighted graphs, TMSIN adopts an iterative workflow to infer proteins. At each iterative step, the probability that a shared peptide belongs to a specific protein is calculated by using the Bayes' law based on the neighbor protein support scores of each protein which are mapped by the shared peptides. We carried out experiments on yeast data and human data to evaluate the performance of TMSIN in terms of ROC, q-value, and accuracy. The experimental results show that AUC scores yielded by TMSIN are 0.742 and 0.874 in yeast dataset and human dataset, respectively, and TMSIN yields the maximum number of true positives when q-value less than or equal to 0.05. The overlap analysis shows that TMSIN is an effective complementary approach for protein inference.

  17. HIV-specific probabilistic models of protein evolution.

    Directory of Open Access Journals (Sweden)

    David C Nickle

    2007-06-01

    Full Text Available Comparative sequence analyses, including such fundamental bioinformatics techniques as similarity searching, sequence alignment and phylogenetic inference, have become a mainstay for researchers studying type 1 Human Immunodeficiency Virus (HIV-1 genome structure and evolution. Implicit in comparative analyses is an underlying model of evolution, and the chosen model can significantly affect the results. In general, evolutionary models describe the probabilities of replacing one amino acid character with another over a period of time. Most widely used evolutionary models for protein sequences have been derived from curated alignments of hundreds of proteins, usually based on mammalian genomes. It is unclear to what extent these empirical models are generalizable to a very different organism, such as HIV-1-the most extensively sequenced organism in existence. We developed a maximum likelihood model fitting procedure to a collection of HIV-1 alignments sampled from different viral genes, and inferred two empirical substitution models, suitable for describing between-and within-host evolution. Our procedure pools the information from multiple sequence alignments, and provided software implementation can be run efficiently in parallel on a computer cluster. We describe how the inferred substitution models can be used to generate scoring matrices suitable for alignment and similarity searches. Our models had a consistently superior fit relative to the best existing models and to parameter-rich data-driven models when benchmarked on independent HIV-1 alignments, demonstrating evolutionary biases in amino-acid substitution that are unique to HIV, and that are not captured by the existing models. The scoring matrices derived from the models showed a marked difference from common amino-acid scoring matrices. The use of an appropriate evolutionary model recovered a known viral transmission history, whereas a poorly chosen model introduced phylogenetic

  18. Dynamical analysis of yeast protein interaction network during the sake brewing process.

    Science.gov (United States)

    Mirzarezaee, Mitra; Sadeghi, Mehdi; Araabi, Babak N

    2011-12-01

    Proteins interact with each other for performing essential functions of an organism. They change partners to get involved in various processes at different times or locations. Studying variations of protein interactions within a specific process would help better understand the dynamic features of the protein interactions and their functions. We studied the protein interaction network of Saccharomyces cerevisiae (yeast) during the brewing of Japanese sake. In this process, yeast cells are exposed to several stresses. Analysis of protein interaction networks of yeast during this process helps to understand how protein interactions of yeast change during the sake brewing process. We used gene expression profiles of yeast cells for this purpose. Results of our experiments revealed some characteristics and behaviors of yeast hubs and non-hubs and their dynamical changes during the brewing process. We found that just a small portion of the proteins (12.8 to 21.6%) is responsible for the functional changes of the proteins in the sake brewing process. The changes in the number of edges and hubs of the yeast protein interaction networks increase in the first stages of the process and it then decreases at the final stages.

  19. Topology and weights in a protein domain interaction network--a novel way to predict protein interactions.

    Science.gov (United States)

    Wuchty, Stefan

    2006-05-23

    While the analysis of unweighted biological webs as diverse as genetic, protein and metabolic networks allowed spectacular insights in the inner workings of a cell, biological networks are not only determined by their static grid of links. In fact, we expect that the heterogeneity in the utilization of connections has a major impact on the organization of cellular activities as well. We consider a web of interactions between protein domains of the Protein Family database (PFAM), which are weighted by a probability score. We apply metrics that combine the static layout and the weights of the underlying interactions. We observe that unweighted measures as well as their weighted counterparts largely share the same trends in the underlying domain interaction network. However, we only find weak signals that weights and the static grid of interactions are connected entities. Therefore assuming that a protein interaction is governed by a single domain interaction, we observe strong and significant correlations of the highest scoring domain interaction and the confidence of protein interactions in the underlying interactions of yeast and fly. Modeling an interaction between proteins if we find a high scoring protein domain interaction we obtain 1, 428 protein interactions among 361 proteins in the human malaria parasite Plasmodium falciparum. Assessing their quality by a logistic regression method we observe that increasing confidence of predicted interactions is accompanied by high scoring domain interactions and elevated levels of functional similarity and evolutionary conservation. Our results indicate that probability scores are randomly distributed, allowing to treat static grid and weights of domain interactions as separate entities. In particular, these finding confirms earlier observations that a protein interaction is a matter of a single interaction event on domain level. As an immediate application, we show a simple way to predict potential protein interactions

  20. The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

    Science.gov (United States)

    Goldman, Aaron David; Beatty, Joshua T; Landweber, Laura F

    2016-01-01

    The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

  1. [Structure and evolution of the eukaryotic FANCJ-like proteins].

    Science.gov (United States)

    Wuhe, Jike; Zefeng, Wu; Sanhong, Fan; Xuguang, Xi

    2015-02-01

    The FANCJ-like protein family is a class of ATP-dependent helicases that can catalytically unwind duplex DNA along the 5'-3' direction. It is involved in the processes of DNA damage repair, homologous recombination and G-quadruplex DNA unwinding, and plays a critical role in maintaining genome integrity. In this study, we systemically analyzed FNACJ-like proteins from 47 eukaryotic species and discussed their sequences diversity, origin and evolution, motif organization patterns and spatial structure differences. Four members of FNACJ-like proteins, including XPD, CHL1, RTEL1 and FANCJ, were found in eukaryotes, but some of them were seriously deficient in most fungi and some insects. For example, the Zygomycota fungi lost RTEL1, Basidiomycota and Ascomycota fungi lost RTEL1 and FANCJ, and Diptera insect lost FANCJ. FANCJ-like proteins contain canonical motor domains HD1 and HD2, and the HD1 domain further integrates with three unique domains Fe-S, Arch and Extra-D. Fe-S and Arch domains are relatively conservative in all members of the family, but the Extra-D domain is lost in XPD and differs from one another in rest members. There are 7, 10 and 2 specific motifs found from the three unique domains respectively, while 5 and 12 specific motifs are found from HD1 and HD2 domains except the conserved motifs reported previously. By analyzing the arrangement pattern of these specific motifs, we found that RTEL1 and FANCJ are more closer and share two specific motifs Vb2 and Vc in HD2 domain, which are likely related with their G-quadruplex DNA unwinding activity. The evidence of evolution showed that FACNJ-like proteins were originated from a helicase, which has a HD1 domain inserted by extra Fe-S domain and Arch domain. By three continuous gene duplication events and followed specialization, eukaryotes finally possessed the current four members of FANCJ-like proteins.

  2. Coiled-Coil Proteins Facilitated the Functional Expansion of the Centrosome

    Science.gov (United States)

    Kuhn, Michael; Hyman, Anthony A.; Beyer, Andreas

    2014-01-01

    Repurposing existing proteins for new cellular functions is recognized as a main mechanism of evolutionary innovation, but its role in organelle evolution is unclear. Here, we explore the mechanisms that led to the evolution of the centrosome, an ancestral eukaryotic organelle that expanded its functional repertoire through the course of evolution. We developed a refined sequence alignment technique that is more sensitive to coiled coil proteins, which are abundant in the centrosome. For proteins with high coiled-coil content, our algorithm identified 17% more reciprocal best hits than BLAST. Analyzing 108 eukaryotic genomes, we traced the evolutionary history of centrosome proteins. In order to assess how these proteins formed the centrosome and adopted new functions, we computationally emulated evolution by iteratively removing the most recently evolved proteins from the centrosomal protein interaction network. Coiled-coil proteins that first appeared in the animal–fungi ancestor act as scaffolds and recruit ancestral eukaryotic proteins such as kinases and phosphatases to the centrosome. This process created a signaling hub that is crucial for multicellular development. Our results demonstrate how ancient proteins can be co-opted to different cellular localizations, thereby becoming involved in novel functions. PMID:24901223

  3. Scalable rule-based modelling of allosteric proteins and biochemical networks.

    Directory of Open Access Journals (Sweden)

    Julien F Ollivier

    2010-11-01

    Full Text Available Much of the complexity of biochemical networks comes from the information-processing abilities of allosteric proteins, be they receptors, ion-channels, signalling molecules or transcription factors. An allosteric protein can be uniquely regulated by each combination of input molecules that it binds. This "regulatory complexity" causes a combinatorial increase in the number of parameters required to fit experimental data as the number of protein interactions increases. It therefore challenges the creation, updating, and re-use of biochemical models. Here, we propose a rule-based modelling framework that exploits the intrinsic modularity of protein structure to address regulatory complexity. Rather than treating proteins as "black boxes", we model their hierarchical structure and, as conformational changes, internal dynamics. By modelling the regulation of allosteric proteins through these conformational changes, we often decrease the number of parameters required to fit data, and so reduce over-fitting and improve the predictive power of a model. Our method is thermodynamically grounded, imposes detailed balance, and also includes molecular cross-talk and the background activity of enzymes. We use our Allosteric Network Compiler to examine how allostery can facilitate macromolecular assembly and how competitive ligands can change the observed cooperativity of an allosteric protein. We also develop a parsimonious model of G protein-coupled receptors that explains functional selectivity and can predict the rank order of potency of agonists acting through a receptor. Our methodology should provide a basis for scalable, modular and executable modelling of biochemical networks in systems and synthetic biology.

  4. PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways

    OpenAIRE

    Mi, Huaiyu; Guo, Nan; Kejariwal, Anish; Thomas, Paul D.

    2006-01-01

    PANTHER is a freely available, comprehensive software system for relating protein sequence evolution to the evolution of specific protein functions and biological roles. Since 2005, there have been three main improvements to PANTHER. First, the sequences used to create evolutionary trees are carefully selected to provide coverage of phylogenetic as well as functional information. Second, PANTHER is now a member of the InterPro Consortium, and the PANTHER hidden markov Models (HMMs) are distri...

  5. Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

    International Nuclear Information System (INIS)

    Ba, Qian; Li, Junyang; Huang, Chao; Li, Jingquan; Chu, Ruiai; Wu, Yongning; Wang, Hui

    2015-01-01

    Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified

  6. Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

    Energy Technology Data Exchange (ETDEWEB)

    Ba, Qian [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Li, Junyang; Huang, Chao [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Li, Jingquan; Chu, Ruiai [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wu, Yongning, E-mail: wuyongning@cfsa.net.cn [Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wang, Hui, E-mail: huiwang@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); School of Life Science and Technology, ShanghaiTech University, Shanghai (China)

    2015-03-01

    Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified.

  7. Evolution of tag-based cooperation with emotion on complex networks

    Science.gov (United States)

    Lima, F. W. S.

    2018-04-01

    We study the evolution of the four strategies: Ethnocentric, altruistic, egoistic and cosmopolitan in one community of individuals through Monte Carlo simulations. Interactions and reproduction among computational agents are simulated on undirected Barabási-Albert (UBA) networks and Erdös-Rènyi random graphs (ER).We study the Hammond-Axelrod model on both UBA networks and ER random graphs for the asexual reproduction case. We use a modified version of the traditional Hammond-Axelrod model and we also allow the agents’ decisions about one of the strategies to take into account the emotion among their equals. Our simulations showed that egoism and altruism win, differently from other results found in the literature where ethnocentric strategy is common.

  8. P³DB 3.0: From plant phosphorylation sites to protein networks.

    Science.gov (United States)

    Yao, Qiuming; Ge, Huangyi; Wu, Shangquan; Zhang, Ning; Chen, Wei; Xu, Chunhui; Gao, Jianjiong; Thelen, Jay J; Xu, Dong

    2014-01-01

    In the past few years, the Plant Protein Phosphorylation Database (P(3)DB, http://p3db.org) has become one of the most significant in vivo data resources for studying plant phosphoproteomics. We have substantially updated P(3)DB with respect to format, new datasets and analytic tools. In the P(3)DB 3.0, there are altogether 47 923 phosphosites in 16 477 phosphoproteins curated across nine plant organisms from 32 studies, which have met our multiple quality standards for acquisition of in vivo phosphorylation site data. Centralized by these phosphorylation data, multiple related data and annotations are provided, including protein-protein interaction (PPI), gene ontology, protein tertiary structures, orthologous sequences, kinase/phosphatase classification and Kinase Client Assay (KiC Assay) data--all of which provides context for the phosphorylation event. In addition, P(3)DB 3.0 incorporates multiple network viewers for the above features, such as PPI network, kinase-substrate network, phosphatase-substrate network, and domain co-occurrence network to help study phosphorylation from a systems point of view. Furthermore, the new P(3)DB reflects a community-based design through which users can share datasets and automate data depository processes for publication purposes. Each of these new features supports the goal of making P(3)DB a comprehensive, systematic and interactive platform for phosphoproteomics research.

  9. DSTATCOM allocation in distribution networks considering reconfiguration using differential evolution algorithm

    International Nuclear Information System (INIS)

    Jazebi, S.; Hosseinian, S.H.; Vahidi, B.

    2011-01-01

    Highlights: → Reconfiguration and DSTATCOM allocation are implemented for RDS planning. → Differential evolution algorithm is applied to solve the nonlinear problem. → Optimal status of tie switches, DSTATCOM size and location are determined. → The goal is to minimize network losses and to improve voltage profile. → The results show the effectiveness of the proposed method to satisfy objectives. -- Abstract: The main idea in distribution network reconfiguration is usually to reduce loss by changing the status of sectionalizing switches and determining appropriate tie switches. Recently Distribution FACTS (DFACTS) devices such as DSTATCOM also have been planned for loss reduction and voltage profile improvement in steady state conditions. This paper implements a combinatorial process based on reconfiguration and DSTATCOM allocation in order to mitigate losses and improve voltage profile in power distribution networks. The distribution system tie switches, DSTATCOM location and size have been optimally determined to obtain an appropriate operational condition. Differential evolution algorithm (DEA) has been used to solve and overcome the complicity of this combinatorial nonlinear optimization problem. To validate the accuracy of results a comparison with particle swarm optimization (PSO) has been made. Simulations have been applied on 69 and 83 busses distribution test systems. All optimization results show the effectiveness of the combinatorial approach in loss reduction and voltage profile improvement.

  10. Large-scale transportation network congestion evolution prediction using deep learning theory.

    Science.gov (United States)

    Ma, Xiaolei; Yu, Haiyang; Wang, Yunpeng; Wang, Yinhai

    2015-01-01

    Understanding how congestion at one location can cause ripples throughout large-scale transportation network is vital for transportation researchers and practitioners to pinpoint traffic bottlenecks for congestion mitigation. Traditional studies rely on either mathematical equations or simulation techniques to model traffic congestion dynamics. However, most of the approaches have limitations, largely due to unrealistic assumptions and cumbersome parameter calibration process. With the development of Intelligent Transportation Systems (ITS) and Internet of Things (IoT), transportation data become more and more ubiquitous. This triggers a series of data-driven research to investigate transportation phenomena. Among them, deep learning theory is considered one of the most promising techniques to tackle tremendous high-dimensional data. This study attempts to extend deep learning theory into large-scale transportation network analysis. A deep Restricted Boltzmann Machine and Recurrent Neural Network architecture is utilized to model and predict traffic congestion evolution based on Global Positioning System (GPS) data from taxi. A numerical study in Ningbo, China is conducted to validate the effectiveness and efficiency of the proposed method. Results show that the prediction accuracy can achieve as high as 88% within less than 6 minutes when the model is implemented in a Graphic Processing Unit (GPU)-based parallel computing environment. The predicted congestion evolution patterns can be visualized temporally and spatially through a map-based platform to identify the vulnerable links for proactive congestion mitigation.

  11. Comparative Genomics Identifies Epidermal Proteins Associated with the Evolution of the Turtle Shell.

    Science.gov (United States)

    Holthaus, Karin Brigit; Strasser, Bettina; Sipos, Wolfgang; Schmidt, Heiko A; Mlitz, Veronika; Sukseree, Supawadee; Weissenbacher, Anton; Tschachler, Erwin; Alibardi, Lorenzo; Eckhart, Leopold

    2016-03-01

    The evolution of reptiles, birds, and mammals was associated with the origin of unique integumentary structures. Studies on lizards, chicken, and humans have suggested that the evolution of major structural proteins of the outermost, cornified layers of the epidermis was driven by the diversification of a gene cluster called Epidermal Differentiation Complex (EDC). Turtles have evolved unique defense mechanisms that depend on mechanically resilient modifications of the epidermis. To investigate whether the evolution of the integument in these reptiles was associated with specific adaptations of the sequences and expression patterns of EDC-related genes, we utilized newly available genome sequences to determine the epidermal differentiation gene complement of turtles. The EDC of the western painted turtle (Chrysemys picta bellii) comprises more than 100 genes, including at least 48 genes that encode proteins referred to as beta-keratins or corneous beta-proteins. Several EDC proteins have evolved cysteine/proline contents beyond 50% of total amino acid residues. Comparative genomics suggests that distinct subfamilies of EDC genes have been expanded and partly translocated to loci outside of the EDC in turtles. Gene expression analysis in the European pond turtle (Emys orbicularis) showed that EDC genes are differentially expressed in the skin of the various body sites and that a subset of beta-keratin genes within the EDC as well as those located outside of the EDC are expressed predominantly in the shell. Our findings give strong support to the hypothesis that the evolutionary innovation of the turtle shell involved specific molecular adaptations of epidermal differentiation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  12. The Oncogenic Palmitoyi-Protein Network in Prostate Cancer

    Science.gov (United States)

    2015-06-01

    was performed by comparing LFQ intensities computed by MaxQuant.16 After statistical analysis, we identified 29 significantly downregulated and 32... statistical analysis, 30 candidate palmitoyl-proteins with an H/L ratio cutoff of 0.667 were accepted as candidate DHHC3 substrates (Table 1). Among...proteomics, we identified a gigantic palmitoyl-protein network regulated by caveolin-1. Moreover, by integrating RNA interference (RNAi), triplex SILAC, and

  13. Evolution and development of brain networks: from Caenorhabditis elegans to Homo sapiens.

    Science.gov (United States)

    Kaiser, Marcus; Varier, Sreedevi

    2011-01-01

    Neural networks show a progressive increase in complexity during the time course of evolution. From diffuse nerve nets in Cnidaria to modular, hierarchical systems in macaque and humans, there is a gradual shift from simple processes involving a limited amount of tasks and modalities to complex functional and behavioral processing integrating different kinds of information from highly specialized tissue. However, studies in a range of species suggest that fundamental similarities, in spatial and topological features as well as in developmental mechanisms for network formation, are retained across evolution. 'Small-world' topology and highly connected regions (hubs) are prevalent across the evolutionary scale, ensuring efficient processing and resilience to internal (e.g. lesions) and external (e.g. environment) changes. Furthermore, in most species, even the establishment of hubs, long-range connections linking distant components, and a modular organization, relies on similar mechanisms. In conclusion, evolutionary divergence leads to greater complexity while following essential developmental constraints.

  14. INTEGRATING GENETIC AND STRUCTURAL DATA ON HUMAN PROTEIN KINOME IN NETWORK-BASED MODELING OF KINASE SENSITIVITIES AND RESISTANCE TO TARGETED AND PERSONALIZED ANTICANCER DRUGS.

    Science.gov (United States)

    Verkhivker, Gennady M

    2016-01-01

    The human protein kinome presents one of the largest protein families that orchestrate functional processes in complex cellular networks, and when perturbed, can cause various cancers. The abundance and diversity of genetic, structural, and biochemical data underlies the complexity of mechanisms by which targeted and personalized drugs can combat mutational profiles in protein kinases. Coupled with the evolution of system biology approaches, genomic and proteomic technologies are rapidly identifying and charactering novel resistance mechanisms with the goal to inform rationale design of personalized kinase drugs. Integration of experimental and computational approaches can help to bring these data into a unified conceptual framework and develop robust models for predicting the clinical drug resistance. In the current study, we employ a battery of synergistic computational approaches that integrate genetic, evolutionary, biochemical, and structural data to characterize the effect of cancer mutations in protein kinases. We provide a detailed structural classification and analysis of genetic signatures associated with oncogenic mutations. By integrating genetic and structural data, we employ network modeling to dissect mechanisms of kinase drug sensitivities to oncogenic EGFR mutations. Using biophysical simulations and analysis of protein structure networks, we show that conformational-specific drug binding of Lapatinib may elicit resistant mutations in the EGFR kinase that are linked with the ligand-mediated changes in the residue interaction networks and global network properties of key residues that are responsible for structural stability of specific functional states. A strong network dependency on high centrality residues in the conformation-specific Lapatinib-EGFR complex may explain vulnerability of drug binding to a broad spectrum of mutations and the emergence of drug resistance. Our study offers a systems-based perspective on drug design by unravelling

  15. Analysis of ribosomal protein gene structures: implications for intron evolution.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Many spliceosomal introns exist in the eukaryotic nuclear genome. Despite much research, the evolution of spliceosomal introns remains poorly understood. In this paper, we tried to gain insights into intron evolution from a novel perspective by comparing the gene structures of cytoplasmic ribosomal proteins (CRPs and mitochondrial ribosomal proteins (MRPs, which are held to be of archaeal and bacterial origin, respectively. We analyzed 25 homologous pairs of CRP and MRP genes that together had a total of 527 intron positions. We found that all 12 of the intron positions shared by CRP and MRP genes resulted from parallel intron gains and none could be considered to be "conserved," i.e., descendants of the same ancestor. This was supported further by the high frequency of proto-splice sites at these shared positions; proto-splice sites are proposed to be sites for intron insertion. Although we could not definitively disprove that spliceosomal introns were already present in the last universal common ancestor, our results lend more support to the idea that introns were gained late. At least, our results show that MRP genes were intronless at the time of endosymbiosis. The parallel intron gains between CRP and MRP genes accounted for 2.3% of total intron positions, which should provide a reliable estimate for future inferences of intron evolution.

  16. The evolution of the protein synthesis system. I - A model of a primitive protein synthesis system

    Science.gov (United States)

    Mizutani, H.; Ponnamperuma, C.

    1977-01-01

    A model is developed to describe the evolution of the protein synthesis system. The model is comprised of two independent autocatalytic systems, one including one gene (A-gene) and two activated amino acid polymerases (O and A-polymerases), and the other including the addition of another gene (N-gene) and a nucleotide polymerase. Simulation results have suggested that even a small enzymic activity and polymerase specificity could lead the system to the most accurate protein synthesis, as far as permitted by transitions to systems with higher accuracy.

  17. Efficient identification of critical residues based only on protein structure by network analysis.

    Directory of Open Access Journals (Sweden)

    Michael P Cusack

    2007-05-01

    Full Text Available Despite the increasing number of published protein structures, and the fact that each protein's function relies on its three-dimensional structure, there is limited access to automatic programs used for the identification of critical residues from the protein structure, compared with those based on protein sequence. Here we present a new algorithm based on network analysis applied exclusively on protein structures to identify critical residues. Our results show that this method identifies critical residues for protein function with high reliability and improves automatic sequence-based approaches and previous network-based approaches. The reliability of the method depends on the conformational diversity screened for the protein of interest. We have designed a web site to give access to this software at http://bis.ifc.unam.mx/jamming/. In summary, a new method is presented that relates critical residues for protein function with the most traversed residues in networks derived from protein structures. A unique feature of the method is the inclusion of the conformational diversity of proteins in the prediction, thus reproducing a basic feature of the structure/function relationship of proteins.

  18. The evolution analysis of listed companies co-holding non-listed financial companies based on two-mode heterogeneous networks

    Science.gov (United States)

    An, Pengli; Li, Huajiao; Zhou, Jinsheng; Chen, Fan

    2017-10-01

    Complex network theory is a widely used tool in the empirical research of financial markets. Two-mode and multi-mode networks are new trends and represent new directions in that they can more accurately simulate relationships between entities. In this paper, we use data for Chinese listed companies holding non-listed financial companies over a ten-year period to construct two networks: a two-mode primitive network in which listed companies and non-listed financial companies are considered actors and events, respectively, and a one-mode network that is constructed based on the decreasing-mode method in which listed companies are considered nodes. We analyze the evolution of the listed company co-holding network from several perspectives, including that of the whole network, of information control ability, of implicit relationships, of community division and of small-world characteristics. The results of the analysis indicate that (1) China's developing stock market affects the share-holding condition of listed companies holding non-listed financial companies; (2) the information control ability of co-holding networks is focused on a few listed companies and the implicit relationship of investment preference between listed companies is determined by the co-holding behavior; (3) the community division of the co-holding network is increasingly obvious, as determined by the investment preferences among listed companies; and (4) the small-world characteristics of the co-holding network are increasingly obvious, resulting in reduced communication costs. In this paper, we conduct an evolution analysis and develop an understanding of the factors that influence the listed companies co-holding network. This study will help illuminate research on evolution analysis.

  19. Sequence motifs in MADS transcription factors responsible for specificity and diversification of protein-protein interaction.

    Directory of Open Access Journals (Sweden)

    Aalt D J van Dijk

    Full Text Available Protein sequences encompass tertiary structures and contain information about specific molecular interactions, which in turn determine biological functions of proteins. Knowledge about how protein sequences define interaction specificity is largely missing, in particular for paralogous protein families with high sequence similarity, such as the plant MADS domain transcription factor family. In comparison to the situation in mammalian species, this important family of transcription regulators has expanded enormously in plant species and contains over 100 members in the model plant species Arabidopsis thaliana. Here, we provide insight into the mechanisms that determine protein-protein interaction specificity for the Arabidopsis MADS domain transcription factor family, using an integrated computational and experimental approach. Plant MADS proteins have highly similar amino acid sequences, but their dimerization patterns vary substantially. Our computational analysis uncovered small sequence regions that explain observed differences in dimerization patterns with reasonable accuracy. Furthermore, we show the usefulness of the method for prediction of MADS domain transcription factor interaction networks in other plant species. Introduction of mutations in the predicted interaction motifs demonstrated that single amino acid mutations can have a large effect and lead to loss or gain of specific interactions. In addition, various performed bioinformatics analyses shed light on the way evolution has shaped MADS domain transcription factor interaction specificity. Identified protein-protein interaction motifs appeared to be strongly conserved among orthologs, indicating their evolutionary importance. We also provide evidence that mutations in these motifs can be a source for sub- or neo-functionalization. The analyses presented here take us a step forward in understanding protein-protein interactions and the interplay between protein sequences and

  20. The evolution of mollusc shells.

    Science.gov (United States)

    McDougall, Carmel; Degnan, Bernard M

    2018-05-01

    Molluscan shells are externally fabricated by specialized epithelial cells on the dorsal mantle. Although a conserved set of regulatory genes appears to underlie specification of mantle progenitor cells, the genes that contribute to the formation of the mature shell are incredibly diverse. Recent comparative analyses of mantle transcriptomes and shell proteomes of gastropods and bivalves are consistent with shell diversity being underpinned by a rapidly evolving mantle secretome (suite of genes expressed in the mantle that encode secreted proteins) that is the product of (a) high rates of gene co-option into and loss from the mantle gene regulatory network, and (b) the rapid evolution of coding sequences, particular those encoding repetitive low complexity domains. Outside a few conserved genes, such as carbonic anhydrase, a so-called "biomineralization toolkit" has yet to be discovered. Despite this, a common suite of protein domains, which are often associated with the extracellular matrix and immunity, appear to have been independently and often uniquely co-opted into the mantle secretomes of different species. The evolvability of the mantle secretome provides a molecular explanation for the evolution and diversity of molluscan shells. These genomic processes are likely to underlie the evolution of other animal biominerals, including coral and echinoderm skeletons. This article is categorized under: Comparative Development and Evolution > Regulation of Organ Diversity Comparative Development and Evolution > Evolutionary Novelties. © 2018 Wiley Periodicals, Inc.

  1. Mean protein evolutionary distance: a method for comparative protein evolution and its application.

    Directory of Open Access Journals (Sweden)

    Michael J Wise

    Full Text Available Proteins are under tight evolutionary constraints, so if a protein changes it can only do so in ways that do not compromise its function. In addition, the proteins in an organism evolve at different rates. Leveraging the history of patristic distance methods, a new method for analysing comparative protein evolution, called Mean Protein Evolutionary Distance (MeaPED, measures differential resistance to evolutionary pressure across viral proteomes and is thereby able to point to the proteins' roles. Different species' proteomes can also be compared because the results, consistent across virus subtypes, concisely reflect the very different lifestyles of the viruses. The MeaPED method is here applied to influenza A virus, hepatitis C virus, human immunodeficiency virus (HIV, dengue virus, rotavirus A, polyomavirus BK and measles, which span the positive and negative single-stranded, doubled-stranded and reverse transcribing RNA viruses, and double-stranded DNA viruses. From this analysis, host interaction proteins including hemagglutinin (influenza, and viroporins agnoprotein (polyomavirus, p7 (hepatitis C and VPU (HIV emerge as evolutionary hot-spots. By contrast, RNA-directed RNA polymerase proteins including L (measles, PB1/PB2 (influenza and VP1 (rotavirus, and internal serine proteases such as NS3 (dengue and hepatitis C virus emerge as evolutionary cold-spots. The hot spot influenza hemagglutinin protein is contrasted with the related cold spot H protein from measles. It is proposed that evolutionary cold-spot proteins can become significant targets for second-line anti-viral therapeutics, in cases where front-line vaccines are not available or have become ineffective due to mutations in the hot-spot, generally more antigenically exposed proteins. The MeaPED package is available from www.pam1.bcs.uwa.edu.au/~michaelw/ftp/src/meaped.tar.gz.

  2. Mean protein evolutionary distance: a method for comparative protein evolution and its application.

    Science.gov (United States)

    Wise, Michael J

    2013-01-01

    Proteins are under tight evolutionary constraints, so if a protein changes it can only do so in ways that do not compromise its function. In addition, the proteins in an organism evolve at different rates. Leveraging the history of patristic distance methods, a new method for analysing comparative protein evolution, called Mean Protein Evolutionary Distance (MeaPED), measures differential resistance to evolutionary pressure across viral proteomes and is thereby able to point to the proteins' roles. Different species' proteomes can also be compared because the results, consistent across virus subtypes, concisely reflect the very different lifestyles of the viruses. The MeaPED method is here applied to influenza A virus, hepatitis C virus, human immunodeficiency virus (HIV), dengue virus, rotavirus A, polyomavirus BK and measles, which span the positive and negative single-stranded, doubled-stranded and reverse transcribing RNA viruses, and double-stranded DNA viruses. From this analysis, host interaction proteins including hemagglutinin (influenza), and viroporins agnoprotein (polyomavirus), p7 (hepatitis C) and VPU (HIV) emerge as evolutionary hot-spots. By contrast, RNA-directed RNA polymerase proteins including L (measles), PB1/PB2 (influenza) and VP1 (rotavirus), and internal serine proteases such as NS3 (dengue and hepatitis C virus) emerge as evolutionary cold-spots. The hot spot influenza hemagglutinin protein is contrasted with the related cold spot H protein from measles. It is proposed that evolutionary cold-spot proteins can become significant targets for second-line anti-viral therapeutics, in cases where front-line vaccines are not available or have become ineffective due to mutations in the hot-spot, generally more antigenically exposed proteins. The MeaPED package is available from www.pam1.bcs.uwa.edu.au/~michaelw/ftp/src/meaped.tar.gz.

  3. How does the antagonism between capping and anti-capping proteins affect actin network dynamics?

    International Nuclear Information System (INIS)

    Hu Longhua; Papoian, Garegin A

    2011-01-01

    Actin-based cell motility is essential to many biological processes. We built a simplified, three-dimensional computational model and subsequently performed stochastic simulations to study the growth dynamics of lamellipodia-like branched networks. In this work, we shed light on the antagonism between capping and anti-capping proteins in regulating actin dynamics in the filamentous network. We discuss detailed mechanisms by which capping and anti-capping proteins affect the protrusion speed of the actin network and the rate of nucleation of filaments. We computed a phase diagram showing the regimes of motility enhancement and inhibition by these proteins. Our work shows that the effects of capping and anti-capping proteins are mainly transmitted by modulation of the filamentous network density and local availability of monomeric actin. We discovered that the combination of the capping/anti-capping regulatory network with nucleation-promoting proteins introduces robustness and redundancy in cell motility machinery, allowing the cell to easily achieve maximal protrusion speeds under a broader set of conditions. Finally, we discuss distributions of filament lengths under various conditions and speculate on their potential implication for the emergence of filopodia from the lamellipodial network.

  4. Intracellular directed evolution of proteins from combinatorial libraries based on conditional phage replication.

    Science.gov (United States)

    Brödel, Andreas K; Jaramillo, Alfonso; Isalan, Mark

    2017-09-01

    Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene-or gene circuit function-that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ∼7 weeks.

  5. Creating a specialist protein resource network: a meeting report for the protein bioinformatics and community resources retreat.

    Science.gov (United States)

    Babbitt, Patricia C; Bagos, Pantelis G; Bairoch, Amos; Bateman, Alex; Chatonnet, Arnaud; Chen, Mark Jinan; Craik, David J; Finn, Robert D; Gloriam, David; Haft, Daniel H; Henrissat, Bernard; Holliday, Gemma L; Isberg, Vignir; Kaas, Quentin; Landsman, David; Lenfant, Nicolas; Manning, Gerard; Nagano, Nozomi; Srinivasan, Narayanaswamy; O'Donovan, Claire; Pruitt, Kim D; Sowdhamini, Ramanathan; Rawlings, Neil D; Saier, Milton H; Sharman, Joanna L; Spedding, Michael; Tsirigos, Konstantinos D; Vastermark, Ake; Vriend, Gerrit

    2015-01-01

    During 11-12 August 2014, a Protein Bioinformatics and Community Resources Retreat was held at the Wellcome Trust Genome Campus in Hinxton, UK. This meeting brought together the principal investigators of several specialized protein resources (such as CAZy, TCDB and MEROPS) as well as those from protein databases from the large Bioinformatics centres (including UniProt and RefSeq). The retreat was divided into five sessions: (1) key challenges, (2) the databases represented, (3) best practices for maintenance and curation, (4) information flow to and from large data centers and (5) communication and funding. An important outcome of this meeting was the creation of a Specialist Protein Resource Network that we believe will improve coordination of the activities of its member resources. We invite further protein database resources to join the network and continue the dialogue.

  6. Evolution of the Converged NGN Service Platforms Towards Future Networks

    Directory of Open Access Journals (Sweden)

    Eugen Mikóczy

    2011-03-01

    Full Text Available This article presents a comparison of main characteristics of the Next Generation Networks (NGN and Future Generation Internet (FGI. The aim is to discuss and compare two approaches to Future Networks (FN and services: the evolution of NGN, and the revolutionary approach of a new FGI. We present both frameworks from the services point of view as they are delivered to the end-user, as well as from the architectural point of view. We compare selected properties of both approaches to explain commonalities and differences. Their challenges are similar: managing the quality of experience, mobility, security, scalability and providing openness to applications. Based on this comparison, we evaluate possible areas for future convergence in the approach of the two architectures to the Future Network concept. Our analysis shows that despite their different backgrounds, the internet’s FGI and telco’s NGN are not that different after all. The convergence of the two approaches therefore seems the only logical way forward.

  7. Convergent evolution of gene networks by single-gene duplications in higher eukaryotes

    OpenAIRE

    Amoutzias, Gregory D; Robertson, David L; Oliver, Stephen G; Bornberg-Bauer, Erich

    2004-01-01

    By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix–loop–helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks e...

  8. Assembly constraints drive co-evolution among ribosomal constituents.

    Science.gov (United States)

    Mallik, Saurav; Akashi, Hiroshi; Kundu, Sudip

    2015-06-23

    Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein-RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein-rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a 'proof of concept' that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Topology and weights in a protein domain interaction network – a novel way to predict protein interactions

    Directory of Open Access Journals (Sweden)

    Wuchty Stefan

    2006-05-01

    Full Text Available Abstract Background While the analysis of unweighted biological webs as diverse as genetic, protein and metabolic networks allowed spectacular insights in the inner workings of a cell, biological networks are not only determined by their static grid of links. In fact, we expect that the heterogeneity in the utilization of connections has a major impact on the organization of cellular activities as well. Results We consider a web of interactions between protein domains of the Protein Family database (PFAM, which are weighted by a probability score. We apply metrics that combine the static layout and the weights of the underlying interactions. We observe that unweighted measures as well as their weighted counterparts largely share the same trends in the underlying domain interaction network. However, we only find weak signals that weights and the static grid of interactions are connected entities. Therefore assuming that a protein interaction is governed by a single domain interaction, we observe strong and significant correlations of the highest scoring domain interaction and the confidence of protein interactions in the underlying interactions of yeast and fly. Modeling an interaction between proteins if we find a high scoring protein domain interaction we obtain 1, 428 protein interactions among 361 proteins in the human malaria parasite Plasmodium falciparum. Assessing their quality by a logistic regression method we observe that increasing confidence of predicted interactions is accompanied by high scoring domain interactions and elevated levels of functional similarity and evolutionary conservation. Conclusion Our results indicate that probability scores are randomly distributed, allowing to treat static grid and weights of domain interactions as separate entities. In particular, these finding confirms earlier observations that a protein interaction is a matter of a single interaction event on domain level. As an immediate application, we

  10. Effect of users' opinion evolution on information diffusion in online social networks

    Science.gov (United States)

    Zhu, Hengmin; Kong, Yuehan; Wei, Jing; Ma, Jing

    2018-02-01

    The process of topic propagation always interweaves information diffusion and opinion evolution, but most previous works studied the models of information diffusion and opinion evolution separately, and seldom focused on their interaction of each other. To shed light on the effect of users' opinion evolution on information diffusion in online social networks, we proposed a model which incorporates opinion evolution into the process of topic propagation. Several real topics propagating on Sina Microblog were collected to analyze individuals' propagation intentions, and different propagation intentions were considered in the model. The topic propagation was simulated to explore the impact of different opinion distributions and intervention with opposite opinion on information diffusion. Results show that the topic with one-sided opinions can spread faster and more widely, and intervention with opposite opinion is an effective measure to guide the topic propagation. The earlier to intervene, the more effectively the topic propagation would be guided.

  11. Identifying protein complex by integrating characteristic of core-attachment into dynamic PPI network.

    Directory of Open Access Journals (Sweden)

    Xianjun Shen

    Full Text Available How to identify protein complex is an important and challenging task in proteomics. It would make great contribution to our knowledge of molecular mechanism in cell life activities. However, the inherent organization and dynamic characteristic of cell system have rarely been incorporated into the existing algorithms for detecting protein complexes because of the limitation of protein-protein interaction (PPI data produced by high throughput techniques. The availability of time course gene expression profile enables us to uncover the dynamics of molecular networks and improve the detection of protein complexes. In order to achieve this goal, this paper proposes a novel algorithm DCA (Dynamic Core-Attachment. It detects protein-complex core comprising of continually expressed and highly connected proteins in dynamic PPI network, and then the protein complex is formed by including the attachments with high adhesion into the core. The integration of core-attachment feature into the dynamic PPI network is responsible for the superiority of our algorithm. DCA has been applied on two different yeast dynamic PPI networks and the experimental results show that it performs significantly better than the state-of-the-art techniques in terms of prediction accuracy, hF-measure and statistical significance in biology. In addition, the identified complexes with strong biological significance provide potential candidate complexes for biologists to validate.

  12. A Deep Learning Network Approach to ab initio Protein Secondary Structure Prediction.

    Science.gov (United States)

    Spencer, Matt; Eickholt, Jesse; Jianlin Cheng

    2015-01-01

    Ab initio protein secondary structure (SS) predictions are utilized to generate tertiary structure predictions, which are increasingly demanded due to the rapid discovery of proteins. Although recent developments have slightly exceeded previous methods of SS prediction, accuracy has stagnated around 80 percent and many wonder if prediction cannot be advanced beyond this ceiling. Disciplines that have traditionally employed neural networks are experimenting with novel deep learning techniques in attempts to stimulate progress. Since neural networks have historically played an important role in SS prediction, we wanted to determine whether deep learning could contribute to the advancement of this field as well. We developed an SS predictor that makes use of the position-specific scoring matrix generated by PSI-BLAST and deep learning network architectures, which we call DNSS. Graphical processing units and CUDA software optimize the deep network architecture and efficiently train the deep networks. Optimal parameters for the training process were determined, and a workflow comprising three separately trained deep networks was constructed in order to make refined predictions. This deep learning network approach was used to predict SS for a fully independent test dataset of 198 proteins, achieving a Q3 accuracy of 80.7 percent and a Sov accuracy of 74.2 percent.

  13. Effect of dataset selection on the topological interpretation of protein interaction networks

    Directory of Open Access Journals (Sweden)

    Robertson David L

    2005-09-01

    Full Text Available Abstract Background Studies of the yeast protein interaction network have revealed distinct correlations between the connectivity of individual proteins within the network and the average connectivity of their neighbours. Although a number of biological mechanisms have been proposed to account for these findings, the significance and influence of the specific datasets included in these studies has not been appreciated adequately. Results We show how the use of different interaction data sets, such as those resulting from high-throughput or small-scale studies, and different modelling methodologies for the derivation pair-wise protein interactions, can dramatically change the topology of these networks. Furthermore, we show that some of the previously reported features identified in these networks may simply be the result of experimental or methodological errors and biases. Conclusion When performing network-based studies, it is essential to define what is meant by the term "interaction" and this must be taken into account when interpreting the topologies of the networks generated. Consideration must be given to the type of data included and appropriate controls that take into account the idiosyncrasies of the data must be selected

  14. Evolution of the Yellow/Major Royal Jelly Protein family and the emergence of social behavior in honey bees.

    Science.gov (United States)

    Drapeau, Mark David; Albert, Stefan; Kucharski, Robert; Prusko, Carsten; Maleszka, Ryszard

    2006-11-01

    The genomic architecture underlying the evolution of insect social behavior is largely a mystery. Eusociality, defined by overlapping generations, parental brood care, and reproductive division of labor, has most commonly evolved in the Hymenopteran insects, including the honey bee Apis mellifera. In this species, the Major Royal Jelly Protein (MRJP) family is required for all major aspects of eusocial behavior. Here, using data obtained from the A. mellifera genome sequencing project, we demonstrate that the MRJP family is encoded by nine genes arranged in an approximately 60-kb tandem array. Furthermore, the MRJP protein family appears to have evolved from a single progenitor gene that encodes a member of the ancient Yellow protein family. Five genes encoding Yellow-family proteins flank the genomic region containing the genes encoding MRJPs. We describe the molecular evolution of these protein families. We then characterize developmental-stage-specific, sex-specific, and caste-specific expression patterns of the mrjp and yellow genes in the honey bee. We review empirical evidence concerning the functions of Yellow proteins in fruit flies and social ants, in order to shed light on the roles of both Yellow and MRJP proteins in A. mellifera. In total, the available evidence suggests that Yellows and MRJPs are multifunctional proteins with diverse, context-dependent physiological and developmental roles. However, many members of the Yellow/MRJP family act as facilitators of reproductive maturation. Finally, it appears that MRJP protein subfamily evolution from the Yellow protein family may have coincided with the evolution of honey bee eusociality.

  15. A Global Protein Kinase and Phosphatase Interaction Network in Yeast

    Science.gov (United States)

    Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

    2011-01-01

    The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

  16. NPPD: A Protein-Protein Docking Scoring Function Based on Dyadic Differences in Networks of Hydrophobic and Hydrophilic Amino Acid Residues

    Directory of Open Access Journals (Sweden)

    Edward S. C. Shih

    2015-03-01

    Full Text Available Protein-protein docking (PPD predictions usually rely on the use of a scoring function to rank docking models generated by exhaustive sampling. To rank good models higher than bad ones, a large number of scoring functions have been developed and evaluated, but the methods used for the computation of PPD predictions remain largely unsatisfactory. Here, we report a network-based PPD scoring function, the NPPD, in which the network consists of two types of network nodes, one for hydrophobic and the other for hydrophilic amino acid residues, and the nodes are connected when the residues they represent are within a certain contact distance. We showed that network parameters that compute dyadic interactions and those that compute heterophilic interactions of the amino acid networks thus constructed allowed NPPD to perform well in a benchmark evaluation of 115 PPD scoring functions, most of which, unlike NPPD, are based on some sort of protein-protein interaction energy. We also showed that NPPD was highly complementary to these energy-based scoring functions, suggesting that the combined use of conventional scoring functions and NPPD might significantly improve the accuracy of current PPD predictions.

  17. Large-scale transportation network congestion evolution prediction using deep learning theory.

    Directory of Open Access Journals (Sweden)

    Xiaolei Ma

    Full Text Available Understanding how congestion at one location can cause ripples throughout large-scale transportation network is vital for transportation researchers and practitioners to pinpoint traffic bottlenecks for congestion mitigation. Traditional studies rely on either mathematical equations or simulation techniques to model traffic congestion dynamics. However, most of the approaches have limitations, largely due to unrealistic assumptions and cumbersome parameter calibration process. With the development of Intelligent Transportation Systems (ITS and Internet of Things (IoT, transportation data become more and more ubiquitous. This triggers a series of data-driven research to investigate transportation phenomena. Among them, deep learning theory is considered one of the most promising techniques to tackle tremendous high-dimensional data. This study attempts to extend deep learning theory into large-scale transportation network analysis. A deep Restricted Boltzmann Machine and Recurrent Neural Network architecture is utilized to model and predict traffic congestion evolution based on Global Positioning System (GPS data from taxi. A numerical study in Ningbo, China is conducted to validate the effectiveness and efficiency of the proposed method. Results show that the prediction accuracy can achieve as high as 88% within less than 6 minutes when the model is implemented in a Graphic Processing Unit (GPU-based parallel computing environment. The predicted congestion evolution patterns can be visualized temporally and spatially through a map-based platform to identify the vulnerable links for proactive congestion mitigation.

  18. The TALE face of Hox proteins in animal evolution.

    Science.gov (United States)

    Merabet, Samir; Galliot, Brigitte

    2015-01-01

    Hox genes are major regulators of embryonic development. One of their most conserved functions is to coordinate the formation of specific body structures along the anterior-posterior (AP) axis in Bilateria. This architectural role was at the basis of several morphological innovations across bilaterian evolution. In this review, we traced the origin of the Hox patterning system by considering the partnership with PBC and Meis proteins. PBC and Meis belong to the TALE-class of homeodomain-containing transcription factors and act as generic cofactors of Hox proteins for AP axis patterning in Bilateria. Recent data indicate that Hox proteins acquired the ability to interact with their TALE partners in the last common ancestor of Bilateria and Cnidaria. These interactions relied initially on a short peptide motif called hexapeptide (HX), which is present in Hox and non-Hox protein families. Remarkably, Hox proteins can also recruit the TALE cofactors by using specific PBC Interaction Motifs (SPIMs). We describe how a functional Hox/TALE patterning system emerged in eumetazoans through the acquisition of SPIMs. We anticipate that interaction flexibility could be found in other patterning systems, being at the heart of the astonishing morphological diversity observed in the animal kingdom.

  19. Network evolution induced by the dynamical rules of two populations

    Science.gov (United States)

    Platini, Thierry; Zia, R. K. P.

    2010-10-01

    We study the dynamical properties of a finite dynamical network composed of two interacting populations, namely extrovert (a) and introvert (b). In our model, each group is characterized by its size (Na and Nb) and preferred degree (κa and \\kappa_b\\ll \\kappa_a ). The network dynamics is governed by the competing microscopic rules of each population that consist of the creation and destruction of links. Starting from an unconnected network, we give a detailed analysis of the mean field approach which is compared to Monte Carlo simulation data. The time evolution of the restricted degrees langkbbrang and langkabrang presents three time regimes and a non-monotonic behavior well captured by our theory. Surprisingly, when the population sizes are equal Na = Nb, the ratio of the restricted degree θ0 = langkabrang/langkbbrang appears to be an integer in the asymptotic limits of the three time regimes. For early times (defined by t introverts remains constant while the number of connections increases linearly in the extrovert population. Finally, due to the competing dynamics, the network presents a frustrated stationary state characterized by a ratio θ0 = 3.

  20. Chaperone-protease networks in mitochondrial protein homeostasis.

    Science.gov (United States)

    Voos, Wolfgang

    2013-02-01

    As essential organelles, mitochondria are intimately integrated into the metabolism of a eukaryotic cell. The maintenance of the functional integrity of the mitochondrial proteome, also termed protein homeostasis, is facing many challenges both under normal and pathological conditions. First, since mitochondria are derived from bacterial ancestor cells, the proteins in this endosymbiotic organelle have a mixed origin. Only a few proteins are encoded on the mitochondrial genome, most genes for mitochondrial proteins reside in the nuclear genome of the host cell. This distribution requires a complex biogenesis of mitochondrial proteins, which are mostly synthesized in the cytosol and need to be imported into the organelle. Mitochondrial protein biogenesis usually therefore comprises complex folding and assembly processes to reach an enzymatically active state. In addition, specific protein quality control (PQC) processes avoid an accumulation of damaged or surplus polypeptides. Mitochondrial protein homeostasis is based on endogenous enzymatic components comprising a diverse set of chaperones and proteases that form an interconnected functional network. This review describes the different types of mitochondrial proteins with chaperone functions and covers the current knowledge of their roles in protein biogenesis, folding, proteolytic removal and prevention of aggregation, the principal reactions of protein homeostasis. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Structure and evolution of the global seafood trade network

    Science.gov (United States)

    Gephart, Jessica A.; Pace, Michael L.

    2015-12-01

    The food production system is increasingly global and seafood is among the most highly traded commodities. Global trade can improve food security by providing access to a greater variety of foods, increasing wealth, buffering against local supply shocks, and benefit the environment by increasing overall use efficiency for some resources. However, global trade can also expose countries to external supply shocks and degrade the environment by increasing resource demand and loosening feedbacks between consumers and the impacts of food production. As a result, changes in global food trade can have important implications for both food security and the environmental impacts of production. Measurements of globalization and the environmental impacts of food production require data on both total trade and the origin and destination of traded goods (the network structure). While the global trade network of agricultural and livestock products has previously been studied, seafood products have been excluded. This study describes the structure and evolution of the global seafood trade network, including metrics quantifying the globalization of seafood, shifts in bilateral trade flows, changes in centrality and comparisons of seafood to agricultural and industrial trade networks. From 1994 to 2012 the number of countries trading in the network remained relatively constant, while the number of trade partnerships increased by over 65%. Over this same period, the total quantity of seafood traded increased by 58% and the value increased 85% in real terms. These changes signify the increasing globalization of seafood products. Additionally, the trade patterns in the network indicate: increased influence of Thailand and China, strengthened intraregional trade, and increased exports from South America and Asia. In addition to characterizing these network changes, this study identifies data needs in order to connect seafood trade with environmental impacts and food security outcomes.

  2. Measuring microscopic evolution processes of complex networks based on empirical data

    International Nuclear Information System (INIS)

    Chi, Liping

    2015-01-01

    Aiming at understanding the microscopic mechanism of complex systems in real world, we perform the measurement that characterizes the evolution properties on two empirical data sets. In the Autonomous Systems Internet data, the network size keeps growing although the system suffers a high rate of node deletion (r = 0.4) and link deletion (q = 0.81). However, the average degree keeps almost unchanged during the whole time range. At each time step the external links attached to a new node are about c = 1.1 and the internal links added between existing nodes are approximately m = 8. For the Scientific Collaboration data, it is a cumulated result of all the authors from 1893 up to the considered year. There is no deletion of nodes and links, r = q = 0. The external and internal links at each time step are c = 1.04 and m = 0, correspondingly. The exponents of degree distribution p(k) ∼ k -γ of these two empirical datasets γ data are in good agreement with that obtained theoretically γ theory . The results indicate that these evolution quantities may provide an insight into capturing the microscopic dynamical processes that govern the network topology. (paper)

  3. Integration and visualization of non-coding RNA and protein interaction networks

    OpenAIRE

    Junge, Alexander; Refsgaard, Jan Christian; Garde, Christian; Pan, Xiaoyong; Santos Delgado, Alberto; Anthon, Christian; Alkan, Ferhat; von Mering, Christian; Workman, Christopher; Jensen, Lars Juhl; Gorodkin, Jan

    2015-01-01

    Non-coding RNAs (ncRNAs) fulfill a diverse set of biological functions relying on interactions with other molecular entities. The advent of new experimental and computational approaches makes it possible to study ncRNAs and their associations on an unprecedented scale. We present RAIN (RNA Association and Interaction Networks) - a database that combines ncRNA-ncRNA, ncRNA-mRNA and ncRNA-protein interactions with large-scale protein association networks available in the STRING database. By int...

  4. Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins

    Science.gov (United States)

    Hu, Yueming; Huang, He; Hui, Xinjie; Cheng, Xi; White, Aaron P.

    2016-01-01

    Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In Yersinia, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by Yersinia genomes or their evolution. In this study, the Yersinia LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 protein-encoding genes (LRR1 genes) varied dramatically and were categorized into 4 subgroups (a to d), with the LRR1a to -c genes evolving from the same ancestor and LRR1d genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of Yersinia. PMID:27217422

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

    Science.gov (United States)

    Mallik, Mrinmay Kumar

    2018-02-07

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

  6. Protein Network Signatures Associated with Exogenous Biofuels Treatments in Cyanobacterium Synechocystis sp. PCC 6803

    International Nuclear Information System (INIS)

    Pei, Guangsheng; Chen, Lei; Wang, Jiangxin; Qiao, Jianjun; Zhang, Weiwen

    2014-01-01

    Although recognized as a promising microbial cell factory for producing biofuels, current productivity in cyanobacterial systems is low. To make the processes economically feasible, one of the hurdles, which need to be overcome is the low tolerance of hosts to toxic biofuels. Meanwhile, little information is available regarding the cellular responses to biofuels stress in cyanobacteria, which makes it challenging for tolerance engineering. Using large proteomic datasets of Synechocystis under various biofuels stress and environmental perturbation, a protein co-expression network was first constructed and then combined with the experimentally determined protein–protein interaction network. Proteins with statistically higher topological overlap in the integrated network were identified as common responsive proteins to both biofuels stress and environmental perturbations. In addition, a weighted gene co-expression network analysis was performed to distinguish unique responses to biofuels from those to environmental perturbations and to uncover metabolic modules and proteins uniquely associated with biofuels stress. The results showed that biofuel-specific proteins and modules were enriched in several functional categories, including photosynthesis, carbon fixation, and amino acid metabolism, which may represent potential key signatures for biofuels stress responses in Synechocystis. Network-based analysis allowed determination of the responses specifically related to biofuels stress, and the results constituted an important knowledge foundation for tolerance engineering against biofuels in Synechocystis.

  7. Protein Network Signatures Associated with Exogenous Biofuels Treatments in Cyanobacterium Synechocystis sp. PCC 6803

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Guangsheng; Chen, Lei; Wang, Jiangxin; Qiao, Jianjun, E-mail: jianjunq@tju.edu.cn; Zhang, Weiwen, E-mail: jianjunq@tju.edu.cn [Laboratory of Synthetic Microbiology, School of Chemical Engineering and Technology, Tianjin University, Tianjin (China); Key Laboratory of Systems Bioengineering, Ministry of Education of China, Tianjin (China); SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin (China)

    2014-11-03

    Although recognized as a promising microbial cell factory for producing biofuels, current productivity in cyanobacterial systems is low. To make the processes economically feasible, one of the hurdles, which need to be overcome is the low tolerance of hosts to toxic biofuels. Meanwhile, little information is available regarding the cellular responses to biofuels stress in cyanobacteria, which makes it challenging for tolerance engineering. Using large proteomic datasets of Synechocystis under various biofuels stress and environmental perturbation, a protein co-expression network was first constructed and then combined with the experimentally determined protein–protein interaction network. Proteins with statistically higher topological overlap in the integrated network were identified as common responsive proteins to both biofuels stress and environmental perturbations. In addition, a weighted gene co-expression network analysis was performed to distinguish unique responses to biofuels from those to environmental perturbations and to uncover metabolic modules and proteins uniquely associated with biofuels stress. The results showed that biofuel-specific proteins and modules were enriched in several functional categories, including photosynthesis, carbon fixation, and amino acid metabolism, which may represent potential key signatures for biofuels stress responses in Synechocystis. Network-based analysis allowed determination of the responses specifically related to biofuels stress, and the results constituted an important knowledge foundation for tolerance engineering against biofuels in Synechocystis.

  8. Advanced path sampling of the kinetic network of small proteins

    NARCIS (Netherlands)

    Du, W.

    2014-01-01

    This thesis is focused on developing advanced path sampling simulation methods to study protein folding and unfolding, and to build kinetic equilibrium networks describing these processes. In Chapter 1 the basic knowledge of protein structure and folding theories were introduced and a brief overview

  9. Six subgroups and extensive recent duplications characterize the evolution of the eukaryotic tubulin protein family.

    Science.gov (United States)

    Findeisen, Peggy; Mühlhausen, Stefanie; Dempewolf, Silke; Hertzog, Jonny; Zietlow, Alexander; Carlomagno, Teresa; Kollmar, Martin

    2014-08-27

    Tubulins belong to the most abundant proteins in eukaryotes providing the backbone for many cellular substructures like the mitotic and meiotic spindles, the intracellular cytoskeletal network, and the axonemes of cilia and flagella. Homologs have even been reported for archaea and bacteria. However, a taxonomically broad and whole-genome-based analysis of the tubulin protein family has never been performed, and thus, the number of subfamilies, their taxonomic distribution, and the exact grouping of the supposed archaeal and bacterial homologs are unknown. Here, we present the analysis of 3,524 tubulins from 504 species. The tubulins formed six major subfamilies, α to ζ. Species of all major kingdoms of the eukaryotes encode members of these subfamilies implying that they must have already been present in the last common eukaryotic ancestor. The proposed archaeal homologs grouped together with the bacterial TubZ proteins as sister clade to the FtsZ proteins indicating that tubulins are unique to eukaryotes. Most species contained α- and/or β-tubulin gene duplicates resulting from recent branch- and species-specific duplication events. This shows that tubulins cannot be used for constructing species phylogenies without resolving their ortholog-paralog relationships. The many gene duplicates and also the independent loss of the δ-, ε-, or ζ-tubulins, which have been shown to be part of the triplet microtubules in basal bodies, suggest that tubulins can functionally substitute each other. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Mining protein interactomes to improve their reliability and support the advancement of network medicine

    KAUST Repository

    Alanis Lobato, Gregorio

    2015-09-23

    High-throughput detection of protein interactions has had a major impact in our understanding of the intricate molecular machinery underlying the living cell, and has permitted the construction of very large protein interactomes. The protein networks that are currently available are incomplete and a significant percentage of their interactions are false positives. Fortunately, the structural properties observed in good quality social or technological networks are also present in biological systems. This has encouraged the development of tools, to improve the reliability of protein networks and predict new interactions based merely on the topological characteristics of their components. Since diseases are rarely caused by the malfunction of a single protein, having a more complete and reliable interactome is crucial in order to identify groups of inter-related proteins involved in disease etiology. These system components can then be targeted with minimal collateral damage. In this article, an important number of network mining tools is reviewed, together with resources from which reliable protein interactomes can be constructed. In addition to the review, a few representative examples of how molecular and clinical data can be integrated to deepen our understanding of pathogenesis are discussed.

  11. Mining protein interactomes to improve their reliability and support the advancement of network medicine

    Directory of Open Access Journals (Sweden)

    Gregorio eAlanis-Lobato

    2015-09-01

    Full Text Available High-throughput detection of protein interactions has had a major impact in our understanding of the intricate molecular machinery underlying the living cell, and has permitted the construction of very large protein interactomes. The protein networks that are currently available are incomplete and a significant percentage of their interactions are false positives. Fortunately, the structural properties observed in good quality social or technological networks are also present in biological systems. This has encouraged the development of tools, to improve the reliability of protein networks and predict new interactions based merely on the topological characteristics of their components. Since diseases are rarely caused by the malfunction of a single protein, having a more complete and reliable interactome is crucial in order to identify groups of inter-related proteins involved in disease aetiology. These system components can then be targeted with minimal collateral damage. In this article, an important number of network mining tools is reviewed, together with resources from which reliable protein interactomes can be constructed. In addition to the review, a few representative examples of how molecular and clinical data can be integrated to deepen our understanding of pathogenesis are discussed.

  12. RRW: repeated random walks on genome-scale protein networks for local cluster discovery

    Directory of Open Access Journals (Sweden)

    Can Tolga

    2009-09-01

    Full Text Available Abstract Background We propose an efficient and biologically sensitive algorithm based on repeated random walks (RRW for discovering functional modules, e.g., complexes and pathways, within large-scale protein networks. Compared to existing cluster identification techniques, RRW implicitly makes use of network topology, edge weights, and long range interactions between proteins. Results We apply the proposed technique on a functional network of yeast genes and accurately identify statistically significant clusters of proteins. We validate the biological significance of the results using known complexes in the MIPS complex catalogue database and well-characterized biological processes. We find that 90% of the created clusters have the majority of their catalogued proteins belonging to the same MIPS complex, and about 80% have the majority of their proteins involved in the same biological process. We compare our method to various other clustering techniques, such as the Markov Clustering Algorithm (MCL, and find a significant improvement in the RRW clusters' precision and accuracy values. Conclusion RRW, which is a technique that exploits the topology of the network, is more precise and robust in finding local clusters. In addition, it has the added flexibility of being able to find multi-functional proteins by allowing overlapping clusters.

  13. Improved Differential Evolution Algorithm for Wireless Sensor Network Coverage Optimization

    Directory of Open Access Journals (Sweden)

    Xing Xu

    2014-04-01

    Full Text Available In order to serve for the ecological monitoring efficiency of Poyang Lake, an improved hybrid algorithm, mixed with differential evolution and particle swarm optimization, is proposed and applied to optimize the coverage problem of wireless sensor network. And then, the affect of the population size and the number of iterations on the coverage performance are both discussed and analyzed. The four kinds of statistical results about the coverage rate are obtained through lots of simulation experiments.

  14. Competition, transmission and pattern evolution: A network analysis of global oil trade

    International Nuclear Information System (INIS)

    Zhang, Hai-Ying; Ji, Qiang; Fan, Ying

    2014-01-01

    This paper studies the competition among oil importers using complex network theory, combined with several alternative measures of competition intensity, to analyze the evolution of the pattern and transmission of oil-trading competition. The results indicate that oil trade has formed a global competition pattern and that the role played by the Asian-Pacific region in the evolution of this competition pattern is becoming increasingly prominent. In addition, global competition intensity has continued to rise, and non-OECD countries have become the main driving force for this increase in global competition intensity. The large oil importers are the most significant parts of the global oil-trading competition pattern. They are not only the major participants in the competition for oil resources but also play important roles in the transmission of oil-trading competition. China and the United States especially display the feature of globalization, whose impacts of transmission reach across the whole oil-trading competition network. Finally, a “5C” (changeability, contestability, cooperation, commitment and circumstances) policy framework is put forward to maintain the stability of oil trade and improve the energy security of oil importers in various aspects. - Highlights: • An oil-trading competition network is constructed using complex network theory. • Oil trade has formed a global competition pattern and its intensity has kept rising. • The status of the Asian-Pacific region in the competition pattern becomes prominent. • Large oil importers play important roles in transmitting the trading competition. • A “5C” policy framework is put forward to cope with the intensive competition

  15. Reconstruction of the yeast protein-protein interaction network involved in nutrient sensing and global metabolic regulation

    DEFF Research Database (Denmark)

    Nandy, Subir Kumar; Jouhten, Paula; Nielsen, Jens

    2010-01-01

    proteins. Despite the value of BioGRID for studying protein-protein interactions, there is a need for manual curation of these interactions in order to remove false positives. RESULTS: Here we describe an annotated reconstruction of the protein-protein interactions around four key nutrient......) and for all the interactions between them (edges). The annotated information is readily available utilizing the functionalities of network modelling tools such as Cytoscape and CellDesigner. CONCLUSIONS: The reported fully annotated interaction model serves as a platform for integrated systems biology studies...

  16. Effect of local information within network layers on the evolution of cooperation in duplex public goods games

    International Nuclear Information System (INIS)

    Zhou, Yifeng; Zheng, Xiaoming; Wu, Weiwei

    2015-01-01

    Traditional works of public goods game (PGG) are often studied in simplex networks where agents play games through the same type of social interactions. In order to promote cooperation against the defection in PGGs in simplex network environment, many mechanisms have been proposed from different perspectives, such as the volunteering mechanisms, and the punishment and reward approaches. However, due to diverse types of interactions between agents in reality, the study of PGG should also consider the characteristic of multiplexity of networks. Hence, we firstly model the public goods game in the duplex network (for simplification of analysis, the duplex network is considered), in which agents have two types of social interactions, and thus the network is modeled as two network layers. This type of PGG is naturally named as duplex public goods game (D-PGG), in which agents can select one of the network layers to allocate their limited resources. Then for the new game environment (D-PGG), we propose a novel perspective to promote cooperation: degrading the information integrity, i.e., agents get information just from one network layer (local information) rather than from the whole duplex network (global information) in the evolution process. Finally, through theoretical analyses and simulations, we find that if agents imitate based on the local information of the payoff in the evolution, cooperation can be generally promoted; and the extent of promotion depends on both the network structure and the similarity of the network layers

  17. Supervised maximum-likelihood weighting of composite protein networks for complex prediction

    Directory of Open Access Journals (Sweden)

    Yong Chern Han

    2012-12-01

    Full Text Available Abstract Background Protein complexes participate in many important cellular functions, so finding the set of existent complexes is essential for understanding the organization and regulation of processes in the cell. With the availability of large amounts of high-throughput protein-protein interaction (PPI data, many algorithms have been proposed to discover protein complexes from PPI networks. However, such approaches are hindered by the high rate of noise in high-throughput PPI data, including spurious and missing interactions. Furthermore, many transient interactions are detected between proteins that are not from the same complex, while not all proteins from the same complex may actually interact. As a result, predicted complexes often do not match true complexes well, and many true complexes go undetected. Results We address these challenges by integrating PPI data with other heterogeneous data sources to construct a composite protein network, and using a supervised maximum-likelihood approach to weight each edge based on its posterior probability of belonging to a complex. We then use six different clustering algorithms, and an aggregative clustering strategy, to discover complexes in the weighted network. We test our method on Saccharomyces cerevisiae and Homo sapiens, and show that complex discovery is improved: compared to previously proposed supervised and unsupervised weighting approaches, our method recalls more known complexes, achieves higher precision at all recall levels, and generates novel complexes of greater functional similarity. Furthermore, our maximum-likelihood approach allows learned parameters to be used to visualize and evaluate the evidence of novel predictions, aiding human judgment of their credibility. Conclusions Our approach integrates multiple data sources with supervised learning to create a weighted composite protein network, and uses six clustering algorithms with an aggregative clustering strategy to

  18. Using sequence similarity networks for visualization of relationships across diverse protein superfamilies.

    Directory of Open Access Journals (Sweden)

    Holly J Atkinson

    Full Text Available The dramatic increase in heterogeneous types of biological data--in particular, the abundance of new protein sequences--requires fast and user-friendly methods for organizing this information in a way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity--GPCRs and kinases from humans, and the crotonase superfamily of enzymes--we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships.

  19. Using sequence similarity networks for visualization of relationships across diverse protein superfamilies.

    Science.gov (United States)

    Atkinson, Holly J; Morris, John H; Ferrin, Thomas E; Babbitt, Patricia C

    2009-01-01

    The dramatic increase in heterogeneous types of biological data--in particular, the abundance of new protein sequences--requires fast and user-friendly methods for organizing this information in a way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity--GPCRs and kinases from humans, and the crotonase superfamily of enzymes--we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships.

  20. Protein-protein networks construction and their relevance measurement based on multi-epitope-ligand-kartographie and gene ontology data of T-cell surface proteins for polymyositis.

    Science.gov (United States)

    Li, Fang-Zhen; Gao, Feng

    2012-08-01

    Polymyositis is an inflammatory myopathy characterized by muscle invasion of T-cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. In order to understand the different adhesive mechanisms at the T-cell surface, Schubert randomly selected 19 proteins expressed at the T-cell surface and studied them using MELK technique [4], among which 15 proteins are picked up for further study by us. Two types of functional similarity networks are constructed for these proteins. The first type is MELK similarity network, which is constructed based on their MELK data by using the McNemar's test [24]. The second type is GO similarity network, which is constructed based on their GO annotation data by using the RSS method to measuring functional similarity. Then the subset surprisology theory is employed to measure the degree of similarity between two networks. Our computing results show that these two types of networks are high related. This conclusion added new values on MELK technique and expanded its applications greatly.

  1. New gene evolution in the bonus-TIF1-γ/TRIM33 family impacted the architecture of the vertebrate dorsal-ventral patterning network.

    Science.gov (United States)

    Wisotzkey, Robert G; Quijano, Janine C; Stinchfield, Michael J; Newfeld, Stuart J

    2014-09-01

    Uncovering how a new gene acquires its function and understanding how the function of a new gene influences existing genetic networks are important topics in evolutionary biology. Here, we demonstrate nonconservation for the embryonic functions of Drosophila Bonus and its newest vertebrate relative TIF1-γ/TRIM33. We showed previously that TIF1-γ/TRIM33 functions as an ubiquitin ligase for the Smad4 signal transducer and antagonizes the Bone Morphogenetic Protein (BMP) signaling network underlying vertebrate dorsal-ventral axis formation. Here, we show that Bonus functions as an agonist of the Decapentaplegic (Dpp) signaling network underlying dorsal-ventral axis formation in flies. The absence of conservation for the roles of Bonus and TIF1-γ/TRIM33 reveals a shift in the dorsal-ventral patterning networks of flies and mice, systems that were previously considered wholly conserved. The shift occurred when the new gene TIF1-γ/TRIM33 replaced the function of the ubiquitin ligase Nedd4L in the lineage leading to vertebrates. Evidence of this replacement is our demonstration that Nedd4 performs the function of TIF1-γ/TRIM33 in flies during dorsal-ventral axis formation. The replacement allowed vertebrate Nedd4L to acquire novel functions as a ubiquitin ligase of vertebrate-specific Smad proteins. Overall our data reveal that the architecture of the Dpp/BMP dorsal-ventral patterning network continued to evolve in the vertebrate lineage, after separation from flies, via the incorporation of new genes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

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

    2017-02-01

    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. Adventures in the evolution of a high-bandwidth network for central servers

    International Nuclear Information System (INIS)

    Swartz, K.L.; Cottrell, L.; Dart, M.

    1994-08-01

    In a small network, clients and servers may all be connected to a single Ethernet without significant performance concerns. As the number of clients on a network grows, the necessity of splitting the network into multiple sub-networks, each with a manageable number of clients, becomes clear. Less obvious is what to do with the servers. Group file servers on subnets and multihomed servers offer only partial solutions -- many other types of servers do not lend themselves to a decentralized model, and tend to collect on another, well-connected but overloaded Ethernet. The higher speed of FDDI seems to offer an easy solution, but in practice both expense and interoperability problems render FDDI a poor choice. Ethernet switches appear to permit cheaper and more reliable networking to the servers while providing an aggregate network bandwidth greater than a simple Ethernet. This paper studies the evolution of the server networks at SLAC. Difficulties encountered in the deployment of FDDI are described, as are the tools and techniques used to characterize the traffic patterns on the server network. Performance of Ethernet, FDDI, and switched Ethernet networks is analyzed, as are reliability and maintainability issues for these alternatives. The motivations for re-designing the SLAC general server network to use a switched Ethernet instead of FDDI are described, as are the reasons for choosing FDDI for the farm and firewall networks at SLAC. Guidelines are developed which may help in making this choice for other networks

  4. SLiMScape 3.x: a Cytoscape 3 app for discovery of Short Linear Motifs in protein interaction networks [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Emily Olorin

    2015-08-01

    Full Text Available Short linear motifs (SLiMs are small protein sequence patterns that mediate a large number of critical protein-protein interactions, involved in processes such as complex formation, signal transduction, localisation and stabilisation. SLiMs show rapid evolutionary dynamics and are frequently the targets of molecular mimicry by pathogens. Identifying enriched sequence patterns due to convergent evolution in non-homologous proteins has proven to be a successful strategy for computational SLiM prediction. Tools of the SLiMSuite package use this strategy, using a statistical model to identify SLiM enrichment based on the evolutionary relationships, amino acid composition and predicted disorder of the input proteins. The quality of input data is critical for successful SLiM prediction. Cytoscape provides a user-friendly, interactive environment to explore interaction networks and select proteins based on common features, such as shared interaction partners. SLiMScape embeds tools of the SLiMSuite package for de novo SLiM discovery (SLiMFinder and QSLiMFinder and identifying occurrences/enrichment of known SLiMs (SLiMProb within this interactive framework. SLiMScape makes it easier to (1 generate high quality hypothesis-driven datasets for these tools, and (2 visualise predicted SLiM occurrences within the context of the network. To generate new predictions, users can select nodes from a protein network or provide a set of Uniprot identifiers. SLiMProb also requires additional query motif input. Jobs are then run remotely on the SLiMSuite server (http://rest.slimsuite.unsw.edu.au for subsequent retrieval and visualisation. SLiMScape can also be used to retrieve and visualise results from jobs run directly on the server. SLiMScape and SLiMSuite are open source and freely available via GitHub under GNU licenses.

  5. Energy-Aware Topology Evolution Model with Link and Node Deletion in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Xiaojuan Luo

    2012-01-01

    Full Text Available Based on the complex network theory, a new topological evolving model is proposed. In the evolution of the topology of sensor networks, the energy-aware mechanism is taken into account, and the phenomenon of change of the link and node in the network is discussed. Theoretical analysis and numerical simulation are conducted to explore the topology characteristics and network performance with different node energy distribution. We find that node energy distribution has the weak effect on the degree distribution P(k that evolves into the scale-free state, nodes with more energy carry more connections, and degree correlation is nontrivial disassortative. Moreover, the results show that, when nodes energy is more heterogeneous, the network is better clustered and enjoys higher performance in terms of the network efficiency and the average path length for transmitting data.

  6. Evolution of EF-hand calcium-modulated proteins. IV. Exon shuffling did not determine the domain compositions of EF-hand proteins

    Science.gov (United States)

    Kretsinger, R. H.; Nakayama, S.

    1993-01-01

    In the previous three reports in this series we demonstrated that the EF-hand family of proteins evolved by a complex pattern of gene duplication, transposition, and splicing. The dendrograms based on exon sequences are nearly identical to those based on protein sequences for troponin C, the essential light chain myosin, the regulatory light chain, and calpain. This validates both the computational methods and the dendrograms for these subfamilies. The proposal of congruence for calmodulin, troponin C, essential light chain, and regulatory light chain was confirmed. There are, however, significant differences in the calmodulin dendrograms computed from DNA and from protein sequences. In this study we find that introns are distributed throughout the EF-hand domain and the interdomain regions. Further, dendrograms based on intron type and distribution bear little resemblance to those based on protein or on DNA sequences. We conclude that introns are inserted, and probably deleted, with relatively high frequency. Further, in the EF-hand family exons do not correspond to structural domains and exon shuffling played little if any role in the evolution of this widely distributed homolog family. Calmodulin has had a turbulent evolution. Its dendrograms based on protein sequence, exon sequence, 3'-tail sequence, intron sequences, and intron positions all show significant differences.

  7. Evolution of egoism on semi-directed and undirected Barabási-Albert networks

    Science.gov (United States)

    Lima, F. W. S.

    2015-05-01

    Through Monte Carlo simulations, we study the evolution of the four strategies: Ethnocentric, altruistic, egoistic and cosmopolitan in one community of individuals. Interactions and reproduction among computational agents are simulated on undirected and semi-directed Barabási-Albert (BA) networks. We study the Hammond-Axelrod (HA) model on undirected and semi-directed BA networks for the asexual reproduction case. With a small modification in the traditional HA model, our simulations showed that egoism wins, differently from other results found in the literature where ethnocentric strategy is common. Here, mechanisms such as reciprocity are absent.

  8. Protein-Protein Interaction Article Classification Using a Convolutional Recurrent Neural Network with Pre-trained Word Embeddings.

    Science.gov (United States)

    Matos, Sérgio; Antunes, Rui

    2017-12-13

    Curation of protein interactions from scientific articles is an important task, since interaction networks are essential for the understanding of biological processes associated with disease or pharmacological action for example. However, the increase in the number of publications that potentially contain relevant information turns this into a very challenging and expensive task. In this work we used a convolutional recurrent neural network for identifying relevant articles for extracting information regarding protein interactions. Using the BioCreative III Article Classification Task dataset, we achieved an area under the precision-recall curve of 0.715 and a Matthew's correlation coefficient of 0.600, which represents an improvement over previous works.

  9. Exploring the Ligand-Protein Networks in Traditional Chinese Medicine: Current Databases, Methods, and Applications

    Directory of Open Access Journals (Sweden)

    Mingzhu Zhao

    2013-01-01

    Full Text Available The traditional Chinese medicine (TCM, which has thousands of years of clinical application among China and other Asian countries, is the pioneer of the “multicomponent-multitarget” and network pharmacology. Although there is no doubt of the efficacy, it is difficult to elucidate convincing underlying mechanism of TCM due to its complex composition and unclear pharmacology. The use of ligand-protein networks has been gaining significant value in the history of drug discovery while its application in TCM is still in its early stage. This paper firstly surveys TCM databases for virtual screening that have been greatly expanded in size and data diversity in recent years. On that basis, different screening methods and strategies for identifying active ingredients and targets of TCM are outlined based on the amount of network information available, both on sides of ligand bioactivity and the protein structures. Furthermore, applications of successful in silico target identification attempts are discussed in detail along with experiments in exploring the ligand-protein networks of TCM. Finally, it will be concluded that the prospective application of ligand-protein networks can be used not only to predict protein targets of a small molecule, but also to explore the mode of action of TCM.

  10. Parallel protein secondary structure prediction based on neural networks.

    Science.gov (United States)

    Zhong, Wei; Altun, Gulsah; Tian, Xinmin; Harrison, Robert; Tai, Phang C; Pan, Yi

    2004-01-01

    Protein secondary structure prediction has a fundamental influence on today's bioinformatics research. In this work, binary and tertiary classifiers of protein secondary structure prediction are implemented on Denoeux belief neural network (DBNN) architecture. Hydrophobicity matrix, orthogonal matrix, BLOSUM62 and PSSM (position specific scoring matrix) are experimented separately as the encoding schemes for DBNN. The experimental results contribute to the design of new encoding schemes. New binary classifier for Helix versus not Helix ( approximately H) for DBNN produces prediction accuracy of 87% when PSSM is used for the input profile. The performance of DBNN binary classifier is comparable to other best prediction methods. The good test results for binary classifiers open a new approach for protein structure prediction with neural networks. Due to the time consuming task of training the neural networks, Pthread and OpenMP are employed to parallelize DBNN in the hyperthreading enabled Intel architecture. Speedup for 16 Pthreads is 4.9 and speedup for 16 OpenMP threads is 4 in the 4 processors shared memory architecture. Both speedup performance of OpenMP and Pthread is superior to that of other research. With the new parallel training algorithm, thousands of amino acids can be processed in reasonable amount of time. Our research also shows that hyperthreading technology for Intel architecture is efficient for parallel biological algorithms.

  11. Recruitment of pre-existing networks during the evolution of C4 photosynthesis.

    Science.gov (United States)

    Reyna-Llorens, Ivan; Hibberd, Julian M

    2017-09-26

    During C 4 photosynthesis, CO 2 is concentrated around the enzyme RuBisCO. The net effect is to reduce photorespiration while increasing water and nitrogen use efficiencies. Species that use C 4 photosynthesis have evolved independently from their C 3 ancestors on more than 60 occasions. Along with mimicry and the camera-like eye, the C 4 pathway therefore represents a remarkable example of the repeated evolution of a highly complex trait. In this review, we provide evidence that the polyphyletic evolution of C 4 photosynthesis is built upon pre-existing metabolic and genetic networks. For example, cells around veins of C 3 species show similarities to those of the C 4 bundle sheath in terms of C 4 acid decarboxylase activity and also the photosynthetic electron transport chain. Enzymes of C 4 photosynthesis function together in gluconeogenesis during early seedling growth of C 3 Arabidopsis thaliana Furthermore, multiple C 4 genes appear to be under control of both light and chloroplast signals in the ancestral C 3 state. We, therefore, hypothesize that relatively minor rewiring of pre-existing genetic and metabolic networks has facilitated the recurrent evolution of this trait. Understanding how these changes are likely to have occurred could inform attempts to install C 4 traits into C 3 crops.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'. © 2017 The Author(s).

  12. Evolution of coauthorship networks: worldwide scientific production on leishmaniasis

    Directory of Open Access Journals (Sweden)

    Gregorio Gonzalez-Alcaide

    2013-12-01

    Full Text Available Introduction Collaboration is one of the defining features of contemporary scientific research, and it is particularly important with regard to neglected diseases that primarily affect developing countries. Methods The present study has identified publications on leishmaniasis in the Medline database from 1945 to 2010, analyzing them according to bibliometric indicators and statistics from social network analysis. Examining aspects such as scientific production, diachronic evolution, and collaboration and configuration of the research groups in the field, we have considered the different types of Leishmania studied and the institutional affiliation and nationality of the authors. Results Seven-hundred and thirty-five authors participate in 154 prominent research clusters or groups. Although the most predominant and consolidated collaborations are characterized by members from the same country studying the same type of Leishmania, there are also notable links between authors from different countries or who study different clinical strains of the disease. Brazil took the lead in this research, with numerous Brazilian researchers heading different clusters in the center of the collaboration network. Investigators from the USA, India, and European countries, such as France, Spain, the United Kingdom, and Italy, also stand out within the network. Conclusions Research should be fostered in countries such as Bangladesh, Nepal, Sudan, and Ethiopia, where there is a high prevalence of different forms of the disease but limited research development with reference authors integrated into the collaboration networks.

  13. A Bipartite Network-based Method for Prediction of Long Non-coding RNA–protein Interactions

    Directory of Open Access Journals (Sweden)

    Mengqu Ge

    2016-02-01

    Full Text Available As one large class of non-coding RNAs (ncRNAs, long ncRNAs (lncRNAs have gained considerable attention in recent years. Mutations and dysfunction of lncRNAs have been implicated in human disorders. Many lncRNAs exert their effects through interactions with the corresponding RNA-binding proteins. Several computational approaches have been developed, but only few are able to perform the prediction of these interactions from a network-based point of view. Here, we introduce a computational method named lncRNA–protein bipartite network inference (LPBNI. LPBNI aims to identify potential lncRNA–interacting proteins, by making full use of the known lncRNA–protein interactions. Leave-one-out cross validation (LOOCV test shows that LPBNI significantly outperforms other network-based methods, including random walk (RWR and protein-based collaborative filtering (ProCF. Furthermore, a case study was performed to demonstrate the performance of LPBNI using real data in predicting potential lncRNA–interacting proteins.

  14. Exploring the patterns and evolution of self-organized urban street networks through modeling

    Science.gov (United States)

    Rui, Yikang; Ban, Yifang; Wang, Jiechen; Haas, Jan

    2013-03-01

    As one of the most important subsystems in cities, urban street networks have recently been well studied by using the approach of complex networks. This paper proposes a growing model for self-organized urban street networks. The model involves a competition among new centers with different values of attraction radius and a local optimal principle of both geometrical and topological factors. We find that with the model growth, the local optimization in the connection process and appropriate probability for the loop construction well reflect the evolution strategy in real-world cities. Moreover, different values of attraction radius in centers competition process lead to morphological change in patterns including urban network, polycentric and monocentric structures. The model succeeds in reproducing a large diversity of road network patterns by varying parameters. The similarity between the properties of our model and empirical results implies that a simple universal growth mechanism exists in self-organized cities.

  15. Scoring protein relationships in functional interaction networks predicted from sequence data.

    Directory of Open Access Journals (Sweden)

    Gaston K Mazandu

    Full Text Available UNLABELLED: The abundance of diverse biological data from various sources constitutes a rich source of knowledge, which has the power to advance our understanding of organisms. This requires computational methods in order to integrate and exploit these data effectively and elucidate local and genome wide functional connections between protein pairs, thus enabling functional inferences for uncharacterized proteins. These biological data are primarily in the form of sequences, which determine functions, although functional properties of a protein can often be predicted from just the domains it contains. Thus, protein sequences and domains can be used to predict protein pair-wise functional relationships, and thus contribute to the function prediction process of uncharacterized proteins in order to ensure that knowledge is gained from sequencing efforts. In this work, we introduce information-theoretic based approaches to score protein-protein functional interaction pairs predicted from protein sequence similarity and conserved protein signature matches. The proposed schemes are effective for data-driven scoring of connections between protein pairs. We applied these schemes to the Mycobacterium tuberculosis proteome to produce a homology-based functional network of the organism with a high confidence and coverage. We use the network for predicting functions of uncharacterised proteins. AVAILABILITY: Protein pair-wise functional relationship scores for Mycobacterium tuberculosis strain CDC1551 sequence data and python scripts to compute these scores are available at http://web.cbio.uct.ac.za/~gmazandu/scoringschemes.

  16. Evolution of the global virtual water trade network.

    Science.gov (United States)

    Dalin, Carole; Konar, Megan; Hanasaki, Naota; Rinaldo, Andrea; Rodriguez-Iturbe, Ignacio

    2012-04-17

    Global freshwater resources are under increasing pressure from economic development, population growth, and climate change. The international trade of water-intensive products (e.g., agricultural commodities) or virtual water trade has been suggested as a way to save water globally. We focus on the virtual water trade network associated with international food trade built with annual trade data and annual modeled virtual water content. The evolution of this network from 1986 to 2007 is analyzed and linked to trade policies, socioeconomic circumstances, and agricultural efficiency. We find that the number of trade connections and the volume of water associated with global food trade more than doubled in 22 years. Despite this growth, constant organizational features were observed in the network. However, both regional and national virtual water trade patterns significantly changed. Indeed, Asia increased its virtual water imports by more than 170%, switching from North America to South America as its main partner, whereas North America oriented to a growing intraregional trade. A dramatic rise in China's virtual water imports is associated with its increased soy imports after a domestic policy shift in 2000. Significantly, this shift has led the global soy market to save water on a global scale, but it also relies on expanding soy production in Brazil, which contributes to deforestation in the Amazon. We find that the international food trade has led to enhanced savings in global water resources over time, indicating its growing efficiency in terms of global water use.

  17. A contribution to the study of plant development evolution based on gene co-expression networks

    Directory of Open Access Journals (Sweden)

    Francisco J. Romero-Campero

    2013-08-01

    Full Text Available Phototrophic eukaryotes are among the most successful organisms on Earth due to their unparalleled efficiency at capturing light energy and fixing carbon dioxide to produce organic molecules. A conserved and efficient network of light-dependent regulatory modules could be at the bases of this success. This regulatory system conferred early advantages to phototrophic eukaryotes that allowed for specialization, complex developmental processes and modern plant characteristics. We have studied light-dependent gene regulatory modules from algae to plants employing integrative-omics approaches based on gene co-expression networks. Our study reveals some remarkably conserved ways in which eukaryotic phototrophs deal with day length and light signaling. Here we describe how a family of Arabidopsis transcription factors involved in photoperiod response has evolved from a single algal gene according to the innovation, amplification and divergence theory of gene evolution by duplication. These modifications of the gene co-expression networks from the ancient unicellular green algae Chlamydomonas reinhardtii to the modern brassica Arabidopsis thaliana may hint on the evolution and specialization of plants and other organisms.

  18. Analysis of hepatocellular carcinoma and metastatic hepatic carcinoma via functional modules in a protein-protein interaction network

    Directory of Open Access Journals (Sweden)

    Jun Pan

    2014-01-01

    Full Text Available Introduction: This study aims to identify protein clusters with potential functional relevance in the pathogenesis of hepatocellular carcinoma (HCC and metastatic hepatic carcinoma using network analysis. Materials and Methods: We used human protein interaction data to build a protein-protein interaction network with Cytoscape and then derived functional clusters using MCODE. Combining the gene expression profiles, we calculated the functional scores for the clusters and selected statistically significant clusters. Meanwhile, Gene Ontology was used to assess the functionality of these clusters. Finally, a support vector machine was trained on the gold standard data sets. Results: The differentially expressed genes of HCC were mainly involved in metabolic and signaling processes. We acquired 13 significant modules from the gene expression profiles. The area under the curve value based on the differentially expressed modules were 98.31%, which outweighed the classification with DEGs. Conclusions: Differentially expressed modules are valuable to screen biomarkers combined with functional modules.

  19. Protein secondary structure prediction using modular reciprocal bidirectional recurrent neural networks.

    Science.gov (United States)

    Babaei, Sepideh; Geranmayeh, Amir; Seyyedsalehi, Seyyed Ali

    2010-12-01

    The supervised learning of recurrent neural networks well-suited for prediction of protein secondary structures from the underlying amino acids sequence is studied. Modular reciprocal recurrent neural networks (MRR-NN) are proposed to model the strong correlations between adjacent secondary structure elements. Besides, a multilayer bidirectional recurrent neural network (MBR-NN) is introduced to capture the long-range intramolecular interactions between amino acids in formation of the secondary structure. The final modular prediction system is devised based on the interactive integration of the MRR-NN and the MBR-NN structures to arbitrarily engage the neighboring effects of the secondary structure types concurrent with memorizing the sequential dependencies of amino acids along the protein chain. The advanced combined network augments the percentage accuracy (Q₃) to 79.36% and boosts the segment overlap (SOV) up to 70.09% when tested on the PSIPRED dataset in three-fold cross-validation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Reconfigurable network systems and software-defined networking

    OpenAIRE

    Zilberman, N.; Watts, P. M.; Rotsos, C.; Moore, A. W.

    2015-01-01

    Modern high-speed networks have evolved from relatively static networks to highly adaptive networks facilitating dynamic reconfiguration. This evolution has influenced all levels of network design and management, introducing increased programmability and configuration flexibility. This influence has extended from the lowest level of physical hardware interfaces to the highest level of network management by software. A key representative of this evolution is the emergence of software-defined n...

  1. A combinatorial approach to detect coevolved amino acid networks in protein families of variable divergence.

    Directory of Open Access Journals (Sweden)

    Julie Baussand

    2009-09-01

    Full Text Available Communication between distant sites often defines the biological role of a protein: amino acid long-range interactions are as important in binding specificity, allosteric regulation and conformational change as residues directly contacting the substrate. The maintaining of functional and structural coupling of long-range interacting residues requires coevolution of these residues. Networks of interaction between coevolved residues can be reconstructed, and from the networks, one can possibly derive insights into functional mechanisms for the protein family. We propose a combinatorial method for mapping conserved networks of amino acid interactions in a protein which is based on the analysis of a set of aligned sequences, the associated distance tree and the combinatorics of its subtrees. The degree of coevolution of all pairs of coevolved residues is identified numerically, and networks are reconstructed with a dedicated clustering algorithm. The method drops the constraints on high sequence divergence limiting the range of applicability of the statistical approaches previously proposed. We apply the method to four protein families where we show an accurate detection of functional networks and the possibility to treat sets of protein sequences of variable divergence.

  2. Limitation of degree information for analyzing the interaction evolution in online social networks

    Science.gov (United States)

    Shang, Ke-Ke; Yan, Wei-Sheng; Xu, Xiao-Ke

    2014-04-01

    Previously many studies on online social networks simply analyze the static topology in which the friend relationship once established, then the links and nodes will not disappear, but this kind of static topology may not accurately reflect temporal interactions on online social services. In this study, we define four types of users and interactions in the interaction (dynamic) network. We found that active, disappeared, new and super nodes (users) have obviously different strength distribution properties and this result also can be revealed by the degree characteristics of the unweighted interaction and friendship (static) networks. However, the active, disappeared, new and super links (interactions) only can be reflected by the strength distribution in the weighted interaction network. This result indicates the limitation of the static topology data on analyzing social network evolutions. In addition, our study uncovers the approximately stable statistics for the dynamic social network in which there are a large variation for users and interaction intensity. Our findings not only verify the correctness of our definitions, but also helped to study the customer churn and evaluate the commercial value of valuable customers in online social networks.

  3. Spatial Organization in Protein Kinase A Signaling Emerged at the Base of Animal Evolution

    NARCIS (Netherlands)

    Peng, Mao; Aye, Thin Thin; Snel, Berend; Van Breukelen, Bas; Scholten, Arjen; Heck, Albert J R

    2015-01-01

    In phosphorylation-directed signaling, spatial and temporal control is organized by complex interaction networks that diligently direct kinases toward distinct substrates to fine-tune specificity. How these protein networks originate and evolve into complex regulatory machineries are among the most

  4. Minimum curvilinearity to enhance topological prediction of protein interactions by network embedding

    KAUST Repository

    Cannistraci, Carlo; Alanis Lobato, Gregorio; Ravasi, Timothy

    2013-01-01

    Motivation: Most functions within the cell emerge thanks to protein-protein interactions (PPIs), yet experimental determination of PPIs is both expensive and time-consuming. PPI networks present significant levels of noise and incompleteness

  5. Evolutionary Analysis of DELLA-Associated Transcriptional Networks

    Directory of Open Access Journals (Sweden)

    Miguel A. Blázquez

    2017-04-01

    Full Text Available DELLA proteins are transcriptional regulators present in all land plants which have been shown to modulate the activity of over 100 transcription factors in Arabidopsis, involved in multiple physiological and developmental processes. It has been proposed that DELLAs transduce environmental information to pre-wired transcriptional circuits because their stability is regulated by gibberellins (GAs, whose homeostasis largely depends on environmental signals. The ability of GAs to promote DELLA degradation coincides with the origin of vascular plants, but the presence of DELLAs in other land plants poses at least two questions: what regulatory properties have DELLAs provided to the behavior of transcriptional networks in land plants, and how has the recruitment of