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      CMIP: a software package capable of reconstructing genome-wide regulatory networks using gene expression data

      research-article
      1 , , 1 , 2 , 3 , 3 , 4 , 3 , , 1 ,
      BMC Bioinformatics
      BioMed Central
      The 27th International Conference on Genome Informatics
      3-5 October 2016
      Gene regulatory network, Genome-wide, Parallel computing, Software

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          Abstract

          Background

          A gene regulatory network (GRN) represents interactions of genes inside a cell or tissue, in which vertexes and edges stand for genes and their regulatory interactions respectively. Reconstruction of gene regulatory networks, in particular, genome-scale networks, is essential for comparative exploration of different species and mechanistic investigation of biological processes. Currently, most of network inference methods are computationally intensive, which are usually effective for small-scale tasks (e.g., networks with a few hundred genes), but are difficult to construct GRNs at genome-scale.

          Results

          Here, we present a software package for gene regulatory network reconstruction at a genomic level, in which gene interaction is measured by the conditional mutual information measurement using a parallel computing framework (so the package is named CMIP). The package is a greatly improved implementation of our previous PCA-CMI algorithm. In CMIP, we provide not only an automatic threshold determination method but also an effective parallel computing framework for network inference. Performance tests on benchmark datasets show that the accuracy of CMIP is comparable to most current network inference methods. Moreover, running tests on synthetic datasets demonstrate that CMIP can handle large datasets especially genome-wide datasets within an acceptable time period. In addition, successful application on a real genomic dataset confirms its practical applicability of the package.

          Conclusions

          This new software package provides a powerful tool for genomic network reconstruction to biological community. The software can be accessed at http://www.picb.ac.cn/CMIP/.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12859-016-1324-y) contains supplementary material, which is available to authorized users.

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          Most cited references24

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          Defining network topologies that can achieve biochemical adaptation.

          Many signaling systems show adaptation-the ability to reset themselves after responding to a stimulus. We computationally searched all possible three-node enzyme network topologies to identify those that could perform adaptation. Only two major core topologies emerge as robust solutions: a negative feedback loop with a buffering node and an incoherent feedforward loop with a proportioner node. Minimal circuits containing these topologies are, within proper regions of parameter space, sufficient to achieve adaptation. More complex circuits that robustly perform adaptation all contain at least one of these topologies at their core. This analysis yields a design table highlighting a finite set of adaptive circuits. Despite the diversity of possible biochemical networks, it may be common to find that only a finite set of core topologies can execute a particular function. These design rules provide a framework for functionally classifying complex natural networks and a manual for engineering networks. For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.
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            Inferring genetic networks and identifying compound mode of action via expression profiling.

            The complexity of cellular gene, protein, and metabolite networks can hinder attempts to elucidate their structure and function. To address this problem, we used systematic transcriptional perturbations to construct a first-order model of regulatory interactions in a nine-gene subnetwork of the SOS pathway in Escherichia coli. The model correctly identified the major regulatory genes and the transcriptional targets of mitomycin C activity in the subnetwork. This approach, which is experimentally and computationally scalable, provides a framework for elucidating the functional properties of genetic networks and identifying molecular targets of pharmacological compounds.
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              Inferring cellular networks using probabilistic graphical models.

              High-throughput genome-wide molecular assays, which probe cellular networks from different perspectives, have become central to molecular biology. Probabilistic graphical models are useful for extracting meaningful biological insights from the resulting data sets. These models provide a concise representation of complex cellular networks by composing simpler submodels. Procedures based on well-understood principles for inferring such models from data facilitate a model-based methodology for analysis and discovery. This methodology and its capabilities are illustrated by several recent applications to gene expression data.
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                Author and article information

                Contributors
                zhenggy@sibs.ac.cn
                lnchen@sibs.ac.cn
                zhuxinguang@picb.ac.cn
                Conference
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                23 December 2016
                23 December 2016
                2016
                : 17
                Issue : Suppl 17 Issue sponsor : Publication of this supplement has not been supported by sponsorship. Information about the source of funding for publication charges can be found in the individual articles. The articles have undergone the journal's standard peer review process for supplements. The Supplement Editors declare that they have no competing interests.
                : 535
                Affiliations
                [1 ]ISNI 0000 0004 0626 5181, GRID grid.464656.3, CAS Key Laboratory of Computational Biology and State Key Laboratory of Hybrid Rice, , CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, ; 320 Yueyang Road, Shanghai, 20031 China
                [2 ]ISNI 0000 0004 0369 6365, GRID grid.22069.3f, Software Engineering Institute, , East China Normal University, ; 3663 North Zhongshan Road, Shanghai, 200062 China
                [3 ]ISNI 0000 0004 0467 2285, GRID grid.419092.7, Key Laboratory of Systems Biology, , Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, ; 320 Yueyang Road, Shanghai, 200031 China
                [4 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, College of Life Science and Biotechnology, , Shanghai Jiaotong University, ; 800 Dongchuan Road, Shanghai, 200240 China
                Article
                1324
                10.1186/s12859-016-1324-y
                5260056
                28155637
                6abf9c5d-a57d-41b7-83e8-dedc3f101243
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                The 27th International Conference on Genome Informatics
                Shanghai, China
                3-5 October 2016
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                © The Author(s) 2016

                Bioinformatics & Computational biology
                gene regulatory network,genome-wide,parallel computing,software

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