629 research outputs found

    Pathway discovery in metabolic networks by subgraph extraction

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    Motivation: Subgraph extraction is a powerful technique to predict pathways from biological networks and a set of query items (e.g. genes, proteins, compounds, etc.). It can be applied to a variety of different data types, such as gene expression, protein levels, operons or phylogenetic profiles. In this article, we investigate different approaches to extract relevant pathways from metabolic networks. Although these approaches have been adapted to metabolic networks, they are generic enough to be adjusted to other biological networks as well

    Mining Representative Unsubstituted Graph Patterns Using Prior Similarity Matrix

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    One of the most powerful techniques to study protein structures is to look for recurrent fragments (also called substructures or spatial motifs), then use them as patterns to characterize the proteins under study. An emergent trend consists in parsing proteins three-dimensional (3D) structures into graphs of amino acids. Hence, the search of recurrent spatial motifs is formulated as a process of frequent subgraph discovery where each subgraph represents a spatial motif. In this scope, several efficient approaches for frequent subgraph discovery have been proposed in the literature. However, the set of discovered frequent subgraphs is too large to be efficiently analyzed and explored in any further process. In this paper, we propose a novel pattern selection approach that shrinks the large number of discovered frequent subgraphs by selecting the representative ones. Existing pattern selection approaches do not exploit the domain knowledge. Yet, in our approach we incorporate the evolutionary information of amino acids defined in the substitution matrices in order to select the representative subgraphs. We show the effectiveness of our approach on a number of real datasets. The results issued from our experiments show that our approach is able to considerably decrease the number of motifs while enhancing their interestingness

    NET-GE: a novel NETwork-based Gene Enrichment for detecting biological processes associated to Mendelian diseases

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    Enrichment analysis is a widely applied procedure for shedding light on the molecular mechanisms and functions at the basis of phenotypes, for enlarging the dataset of possibly related genes/proteins and for helping interpretation and prioritization of newly determined variations. Several standard and Network-based enrichment methods are available. Both approaches rely on the annotations that characterize the genes/proteins included in the input set; network based ones also include in different ways physical and functional relationships among different genes or proteins that can be extracted from the available biological networks of interactions

    Representing and analysing molecular and cellular function in the computer

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    Determining the biological function of a myriad of genes, and understanding how they interact to yield a living cell, is the major challenge of the post genome-sequencing era. The complexity of biological systems is such that this cannot be envisaged without the help of powerful computer systems capable of representing and analysing the intricate networks of physical and functional interactions between the different cellular components. In this review we try to provide the reader with an appreciation of where we stand in this regard. We discuss some of the inherent problems in describing the different facets of biological function, give an overview of how information on function is currently represented in the major biological databases, and describe different systems for organising and categorising the functions of gene products. In a second part, we present a new general data model, currently under development, which describes information on molecular function and cellular processes in a rigorous manner. The model is capable of representing a large variety of biochemical processes, including metabolic pathways, regulation of gene expression and signal transduction. It also incorporates taxonomies for categorising molecular entities, interactions and processes, and it offers means of viewing the information at different levels of resolution, and dealing with incomplete knowledge. The data model has been implemented in the database on protein function and cellular processes 'aMAZE' (http://www.ebi.ac.uk/research/pfbp/), which presently covers metabolic pathways and their regulation. Several tools for querying, displaying, and performing analyses on such pathways are briefly described in order to illustrate the practical applications enabled by the model

    Identification of metabolic pathways using pathfinding approaches: A systematic review

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    Metabolic pathways have become increasingly available for variousmicroorganisms. Such pathways have spurred the development of a wide array of computational tools, in particular, mathematical pathfinding approaches. This article can facilitate the understanding of computational analysis ofmetabolic pathways in genomics. Moreover, stoichiometric and pathfinding approaches inmetabolic pathway analysis are discussed. Threemajor types of studies are elaborated: stoichiometric identification models, pathway-based graph analysis and pathfinding approaches in cellular metabolism. Furthermore, evaluation of the outcomes of the pathways withmathematical benchmarkingmetrics is provided. This review would lead to better comprehension ofmetabolismbehaviors in living cells, in terms of computed pathfinding approaches. © The Author 2016

    Metabolic Network Alignments and their Applications

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    The accumulation of high-throughput genomic and proteomic data allows for the reconstruction of the increasingly large and complex metabolic networks. In order to analyze the accumulated data and reconstructed networks, it is critical to identify network patterns and evolutionary relations between metabolic networks. But even finding similar networks becomes computationally challenging. The dissertation addresses these challenges with discrete optimization and the corresponding algorithmic techniques. Based on the property of the gene duplication and function sharing in biological network,we have formulated the network alignment problem which asks the optimal vertex-to-vertex mapping allowing path contraction, vertex deletion, and vertex insertions. We have proposed the first polynomial time algorithm for aligning an acyclic metabolic pattern pathway with an arbitrary metabolic network. We also have proposed a polynomial-time algorithm for patterns with small treewidth and implemented it for series-parallel patterns which are commonly found among metabolic networks. We have developed the metabolic network alignment tool for free public use. We have performed pairwise mapping of all pathways among five organisms and found a set of statistically significant pathway similarities. We also have applied the network alignment to identifying inconsistency, inferring missing enzymes, and finding potential candidates

    Integrative Analysis of Many Weighted Co-Expression Networks Using Tensor Computation

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

    Evaluating pathway enumeration algorithms in metabolic engineering case studies

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    The design of cell factories for the production of compounds involves the search for suitable heterologous pathways. Different strategies have been proposed to infer such pathways, but most are optimization approaches with specific objective functions, not suited to enumerate multiple pathways. In this work, we analyze two pathway enumeration algorithms based on graph representations: the Solution Structure Generation and the Find Path algorithms. Both are capable of enumerating exhaustively multiple pathways using network topology. We study their capabilities and limitations when designing novel heterologous pathways, by applying these methods on two case studies of synthetic metabolic engineering related to the production of butanol and vanillin
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