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      Bayesian probabilistic network modeling from multiple independent replicates

      research-article
      1 , 2 , , 1
      BMC Bioinformatics
      BioMed Central
      IEEE International Conference on Bioinformatics and Biomedicine 2011
      12-15 November 2011

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          Abstract

          Often protein (or gene) time-course data are collected for multiple replicates. Each replicate generally has sparse data with the number of time points being less than the number of proteins. Usually each replicate is modeled separately. However, here all the information in each of the replicates is used to make a composite inference about signal networks. The composite inference comes from combining well structured Bayesian probabilistic modeling with a multi-faceted Markov Chain Monte Carlo algorithm. Based on simulations which investigate many different types of network interactions and experimental variabilities, the composite examination uncovers many important relationships within the networks. In particular, when the edge's partial correlation between two proteins is at least moderate, then the composite's posterior probability is large.

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          Most cited references13

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          A shrinkage approach to large-scale covariance matrix estimation and implications for functional genomics.

          Inferring large-scale covariance matrices from sparse genomic data is an ubiquitous problem in bioinformatics. Clearly, the widely used standard covariance and correlation estimators are ill-suited for this purpose. As statistically efficient and computationally fast alternative we propose a novel shrinkage covariance estimator that exploits the Ledoit-Wolf (2003) lemma for analytic calculation of the optimal shrinkage intensity. Subsequently, we apply this improved covariance estimator (which has guaranteed minimum mean squared error, is well-conditioned, and is always positive definite even for small sample sizes) to the problem of inferring large-scale gene association networks. We show that it performs very favorably compared to competing approaches both in simulations as well as in application to real expression data.
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            Areas beneath the relative operating characteristics (ROC) and relative operating levels (ROL) curves: Statistical significance and interpretation

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              Discovery of meaningful associations in genomic data using partial correlation coefficients.

              A major challenge of systems biology is to infer biochemical interactions from large-scale observations, such as transcriptomics, proteomics and metabolomics. We propose to use a partial correlation analysis to construct approximate Undirected Dependency Graphs from such large-scale biochemical data. This approach enables a distinction between direct and indirect interactions of biochemical compounds, thereby inferring the underlying network topology. The method is first thoroughly evaluated with a large set of simulated data. Results indicate that the approach has good statistical power and a low False Discovery Rate even in the presence of noise in the data. We then applied the method to an existing data set of yeast gene expression. Several small gene networks were inferred and found to contain genes known to be collectively involved in particular biochemical processes. In some of these networks there are also uncharacterized ORFs present, which lead to hypotheses about their functions. Programs running in MS-Windows and Linux for applying zeroth, first, second and third order partial correlation analysis can be downloaded at: http://mendes.vbi.vt.edu/tiki-index.php?page=Software. Supplementary information can be found at: URL to be decided.
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                Author and article information

                Conference
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central
                1471-2105
                2012
                11 June 2012
                : 13
                : Suppl 9
                : S6
                Affiliations
                [1 ]Department of Mathematics, Wake Forest University, Winston-Salem, North Carolina 27109, USA
                [2 ]Department of Computer Science, Wake Forest University, Winston-Salem, North Carolina 27109, USA
                Article
                1471-2105-13-S9-S6
                10.1186/1471-2105-13-S9-S6
                3372452
                22901091
                94883d69-1c6b-4c3b-a1fa-405b40b06850
                Copyright ©2012 Patton et al; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                IEEE International Conference on Bioinformatics and Biomedicine 2011
                Atlanta, GA, USA
                12-15 November 2011
                History
                Categories
                Proceedings

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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