14,919 research outputs found

    Information content of colored motifs in complex networks

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    We study complex networks in which the nodes of the network are tagged with different colors depending on the functionality of the nodes (colored graphs), using information theory applied to the distribution of motifs in such networks. We find that colored motifs can be viewed as the building blocks of the networks (much more so than the uncolored structural motifs can be) and that the relative frequency with which these motifs appear in the network can be used to define the information content of the network. This information is defined in such a way that a network with random coloration (but keeping the relative number of nodes with different colors the same) has zero color information content. Thus, colored motif information captures the exceptionality of coloring in the motifs that is maintained via selection. We study the motif information content of the C. elegans brain as well as the evolution of colored motif information in networks that reflect the interaction between instructions in genomes of digital life organisms. While we find that colored motif information appears to capture essential functionality in the C. elegans brain (where the color assignment of nodes is straightforward) it is not obvious whether the colored motif information content always increases during evolution, as would be expected from a measure that captures network complexity. For a single choice of color assignment of instructions in the digital life form Avida, we find rather that colored motif information content increases or decreases during evolution, depending on how the genomes are organized, and therefore could be an interesting tool to dissect genomic rearrangements.Comment: 21 pages, 8 figures, to appear in Artificial Lif

    Complex Networks

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    Introduction to the Special Issue on Complex Networks, Artificial Life journal.Comment: 7 pages, in pres

    Finding and counting vertex-colored subtrees

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    The problems studied in this article originate from the Graph Motif problem introduced by Lacroix et al. in the context of biological networks. The problem is to decide if a vertex-colored graph has a connected subgraph whose colors equal a given multiset of colors MM. It is a graph pattern-matching problem variant, where the structure of the occurrence of the pattern is not of interest but the only requirement is the connectedness. Using an algebraic framework recently introduced by Koutis et al., we obtain new FPT algorithms for Graph Motif and variants, with improved running times. We also obtain results on the counting versions of this problem, proving that the counting problem is FPT if M is a set, but becomes W[1]-hard if M is a multiset with two colors. Finally, we present an experimental evaluation of this approach on real datasets, showing that its performance compares favorably with existing software.Comment: Conference version in International Symposium on Mathematical Foundations of Computer Science (MFCS), Brno : Czech Republic (2010) Journal Version in Algorithmic

    DanQ: a hybrid convolutional and recurrent deep neural network for quantifying the function of DNA sequences.

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    Modeling the properties and functions of DNA sequences is an important, but challenging task in the broad field of genomics. This task is particularly difficult for non-coding DNA, the vast majority of which is still poorly understood in terms of function. A powerful predictive model for the function of non-coding DNA can have enormous benefit for both basic science and translational research because over 98% of the human genome is non-coding and 93% of disease-associated variants lie in these regions. To address this need, we propose DanQ, a novel hybrid convolutional and bi-directional long short-term memory recurrent neural network framework for predicting non-coding function de novo from sequence. In the DanQ model, the convolution layer captures regulatory motifs, while the recurrent layer captures long-term dependencies between the motifs in order to learn a regulatory 'grammar' to improve predictions. DanQ improves considerably upon other models across several metrics. For some regulatory markers, DanQ can achieve over a 50% relative improvement in the area under the precision-recall curve metric compared to related models. We have made the source code available at the github repository http://github.com/uci-cbcl/DanQ

    Origin of life in a digital microcosm

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    While all organisms on Earth descend from a common ancestor, there is no consensus on whether the origin of this ancestral self-replicator was a one-off event or whether it was only the final survivor of multiple origins. Here we use the digital evolution system Avida to study the origin of self-replicating computer programs. By using a computational system, we avoid many of the uncertainties inherent in any biochemical system of self-replicators (while running the risk of ignoring a fundamental aspect of biochemistry). We generated the exhaustive set of minimal-genome self-replicators and analyzed the network structure of this fitness landscape. We further examined the evolvability of these self-replicators and found that the evolvability of a self-replicator is dependent on its genomic architecture. We studied the differential ability of replicators to take over the population when competed against each other (akin to a primordial-soup model of biogenesis) and found that the probability of a self-replicator out-competing the others is not uniform. Instead, progenitor (most-recent common ancestor) genotypes are clustered in a small region of the replicator space. Our results demonstrate how computational systems can be used as test systems for hypotheses concerning the origin of life.Comment: 20 pages, 7 figures. To appear in special issue of Philosophical Transactions of the Royal Society A: Re-Conceptualizing the Origins of Life from a Physical Sciences Perspectiv

    Large-scale network organization in the avian forebrain: a connectivity matrix and theoretical analysis

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    Many species of birds, including pigeons, possess demonstrable cognitive capacities, and some are capable of cognitive feats matching those of apes. Since mammalian cortex is laminar while the avian telencephalon is nucleated, it is natural to ask whether the brains of these two cognitively capable taxa, despite their apparent anatomical dissimilarities, might exhibit common principles of organisation on some level. Complementing recent investigations of macro-scale brain connectivity in mammals, including humans and macaques, we here present the first large-scale wiring diagram for the forebrain of a bird. Using graph theory, we show that the pigeon telencephalon is organised along similar lines to that of a mammal. Both are modular, small-world networks with a connective core of hub nodes that includes prefrontal-like and hippocampal structures. These hub nodes are, topologically speaking, the most central regions of the pigeon's brain, as well as being the most richly connected, implying a crucial role in information flow. Overall, our analysis suggests that indeed, despite the absence of cortical layers and close to 300 million years of separate evolution, the connectivity of the avian brain conforms to the same organisational principles as the mammalian brain

    MuxViz: A Tool for Multilayer Analysis and Visualization of Networks

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    Multilayer relationships among entities and information about entities must be accompanied by the means to analyze, visualize, and obtain insights from such data. We present open-source software (muxViz) that contains a collection of algorithms for the analysis of multilayer networks, which are an important way to represent a large variety of complex systems throughout science and engineering. We demonstrate the ability of muxViz to analyze and interactively visualize multilayer data using empirical genetic, neuronal, and transportation networks. Our software is available at https://github.com/manlius/muxViz.Comment: 18 pages, 10 figures (text of the accepted manuscript

    Subgraph covers -- An information theoretic approach to motif analysis in networks

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    Many real world networks contain a statistically surprising number of certain subgraphs, called network motifs. In the prevalent approach to motif analysis, network motifs are detected by comparing subgraph frequencies in the original network with a statistical null model. In this paper we propose an alternative approach to motif analysis where network motifs are defined to be connectivity patterns that occur in a subgraph cover that represents the network using minimal total information. A subgraph cover is defined to be a set of subgraphs such that every edge of the graph is contained in at least one of the subgraphs in the cover. Some recently introduced random graph models that can incorporate significant densities of motifs have natural formulations in terms of subgraph covers and the presented approach can be used to match networks with such models. To prove the practical value of our approach we also present a heuristic for the resulting NP-hard optimization problem and give results for several real world networks.Comment: 10 pages, 7 tables, 1 Figur

    Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

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    The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al
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