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      Information-Theoretic Inference of Large Transcriptional Regulatory Networks

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          Abstract

          The paper presents MRNET, an original method for inferring genetic networks from microarray data. The method is based on maximum relevance/minimum redundancy (MRMR), an effective information-theoretic technique for feature selection in supervised learning. The MRMR principle consists in selecting among the least redundant variables the ones that have the highest mutual information with the target. MRNET extends this feature selection principle to networks in order to infer gene-dependence relationships from microarray data. The paper assesses MRNET by benchmarking it against RELNET, CLR, and ARACNE, three state-of-the-art information-theoretic methods for large (up to several thousands of genes) network inference. Experimental results on thirty synthetically generated microarray datasets show that MRNET is competitive with these methods.

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          Most cited references12

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          Approximating discrete probability distributions with dependence trees

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            Estimation of Entropy and Mutual Information

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              Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks.

              In an effort to find gene regulatory networks and clusters of genes that affect cancer susceptibility to anticancer agents, we joined a database with baseline expression levels of 7,245 genes measured by using microarrays in 60 cancer cell lines, to a database with the amounts of 5,084 anticancer agents needed to inhibit growth of those same cell lines. Comprehensive pair-wise correlations were calculated between gene expression and measures of agent susceptibility. Associations weaker than a threshold strength were removed, leaving networks of highly correlated genes and agents called relevance networks. Hypotheses for potential single-gene determinants of anticancer agent susceptibility were constructed. The effect of random chance in the large number of calculations performed was empirically determined by repeated random permutation testing; only associations stronger than those seen in multiply permuted data were used in clustering. We discuss the advantages of this methodology over alternative approaches, such as phylogenetic-type tree clustering and self-organizing maps.
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                Author and article information

                Journal
                EURASIP J Bioinform Syst Biol
                EURASIP Journal on Bioinformatics and Systems Biology
                BioMed Central
                1687-4145
                1687-4153
                2007
                24 June 2007
                : 2007
                : 1
                : 79879
                Affiliations
                [1 ]ULB Machine Learning Group, Computer Science Department, Université Libre de Bruxelles, Brussels 1050, Belgium
                Article
                1687-4153-2007-79879
                10.1155/2007/79879
                3171353
                18354736
                61058494-d24a-47ba-9538-948530c32b30
                Copyright ©2007 Patrick E. Meyer et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 January 2007
                : 12 May 2007
                Categories
                Research Article

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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