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In this work, we propose a network inference methodology, based on the directed information (DTI) criterion, that incorporates the biology of transcription within the framework so as to enable experimentally verifiable inference. We use publicly available embryonic kidney and T-cell microarray datasets to demonstrate our results. We present two variants of network inference via DTI \u2014 supervised and unsupervised \u2014 and the inferred networks relevant to mammalian nephrogenesis and T-cell activation. Conformity of the obtained interactions with the literature as well as comparison with the coefficient of determination (CoD) method are demonstrated. Apart from network inference, the proposed framework enables the exploration of specific interactions, not just those revealed by data. To illustrate the latter point, a DTI-based framework to resolve interactions between transcription factor modules and target coregulated genes is proposed. Additionally, we show that DTI can be used in conjunction with mutual information to infer higher-order influence networks involving cooperative gene interactions.<\/jats:p>","DOI":"10.1142\/s0219720008003515","type":"journal-article","created":{"date-parts":[[2008,6,23]],"date-time":"2008-06-23T10:01:53Z","timestamp":1214215313000},"page":"493-519","source":"Crossref","is-referenced-by-count":21,"title":["USING DIRECTED INFORMATION TO BUILD BIOLOGICALLY RELEVANT INFLUENCE NETWORKS"],"prefix":"10.1142","volume":"06","author":[{"given":"ARVIND","family":"RAO","sequence":"first","affiliation":[{"name":"Department of Electrical Engineering and Computer Science and Department of Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA"}]},{"suffix":"III","given":"ALFRED O.","family":"HERO","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Science and Department of Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA"}]},{"given":"DAVID J.","family":"STATES","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA"}]},{"given":"JAMES DOUGLAS","family":"ENGEL","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA"}]}],"member":"219","published-online":{"date-parts":[[2011,11,21]]},"reference":[{"key":"rf1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-S1-S7"},{"key":"rf3","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti056"},{"key":"rf4","doi-asserted-by":"publisher","DOI":"10.1109\/TCOM.1973.1091610"},{"key":"rf6","doi-asserted-by":"publisher","DOI":"10.1109\/TIT.2007.896887"},{"key":"rf7","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1982.10477803"},{"key":"rf10","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.23.10263-10276.2004"},{"key":"rf11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0020036"},{"key":"rf12","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh614"},{"key":"rf13","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.2.1558"},{"key":"rf14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh355"},{"key":"rf15","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00043.2005"},{"key":"rf16","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00276.x"},{"key":"rf17","doi-asserted-by":"publisher","DOI":"10.1002\/0471200611"},{"key":"rf19","volume-title":"Advances in Neural Information Processing Systems","volume":"14","author":"Nemenman I.","year":"2002"},{"key":"rf20","doi-asserted-by":"publisher","DOI":"10.1162\/089976603321780272"},{"key":"rf23","doi-asserted-by":"crossref","DOI":"10.1201\/9780429246593","volume-title":"An Introduction to the Bootstrap","author":"Effron B.","year":"1994"},{"key":"rf24","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-7107-7"},{"key":"rf25","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-58716-0"},{"key":"rf26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Benjamini Y.","journal-title":"J. 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