{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:55:47Z","timestamp":1773276947777,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Computational inference methods that make use of graphical models to extract regulatory networks from gene expression data can have difficulty reconstructing dense regions of a network, a consequence of both computational complexity and unreliable parameter estimation when sample size is small. As a result, identification of hub genes is of special difficulty for these methods.<\/jats:p><jats:p>Methods: We present a new algorithm, Empirical Light Mutual Min (ELMM), for large network reconstruction that has properties well suited for recovery of graphs with high-degree nodes. ELMM reconstructs the undirected graph of a regulatory network using empirical Bayes conditional independence testing with a heuristic relaxation of independence constraints in dense areas of the graph. This relaxation allows only one gene of a pair with a putative relation to be aware of the network connection, an approach that is aimed at easing multiple testing problems associated with recovering densely connected structures.<\/jats:p><jats:p>Results: Using in silico data, we show that ELMM has better performance than commonly used network inference algorithms including GeneNet, ARACNE, FOCI, GENIE3 and GLASSO. We also apply ELMM to reconstruct a network among 5492 genes expressed in human lung airway epithelium of healthy non-smokers, healthy smokers and individuals with chronic obstructive pulmonary disease assayed using microarrays. The analysis identifies dense sub-networks that are consistent with known regulatory relationships in the lung airway and also suggests novel hub regulatory relationships among a number of genes that play roles in oxidative stress and secretion.<\/jats:p><jats:p>Availability and implementation: Software for running ELMM is made available at http:\/\/mezeylab.cb.bscb.cornell.edu\/Software.aspx.<\/jats:p><jats:p>Contact: ramimahdi@yahoo.com or jgm45@cornell.edu<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts312","type":"journal-article","created":{"date-parts":[[2012,6,10]],"date-time":"2012-06-10T09:17:39Z","timestamp":1339319859000},"page":"2029-2036","source":"Crossref","is-referenced-by-count":5,"title":["Empirical Bayes conditional independence graphs for regulatory network recovery"],"prefix":"10.1093","volume":"28","author":[{"given":"Rami","family":"Mahdi","sequence":"first","affiliation":[{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"}]},{"given":"Abishek S.","family":"Madduri","sequence":"additional","affiliation":[{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"}]},{"given":"Guoqing","family":"Wang","sequence":"additional","affiliation":[{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"}]},{"given":"Yael","family":"Strulovici-Barel","sequence":"additional","affiliation":[{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"}]},{"given":"Jacqueline","family":"Salit","sequence":"additional","affiliation":[{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"}]},{"given":"Neil R.","family":"Hackett","sequence":"additional","affiliation":[{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"}]},{"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"}]},{"given":"Jason G.","family":"Mezey","sequence":"additional","affiliation":[{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"},{"name":"1 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA and 2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA"}]}],"member":"286","published-online":{"date-parts":[[2012,6,8]]},"reference":[{"key":"2023012512450837500_B1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.cell.2010.11.013","article-title":"An integrated approach to uncover drivers of cancer","volume":"143","author":"Akavia","year":"2010","journal-title":"Cell"},{"key":"2023012512450837500_B2","first-page":"371","article-title":"Causal Explorer:Causal Probabilistic Network Learning Toolkit for Biomedical Discovery","volume-title":"Proceedings of the International Conference on Mathematics and Engineering Techniques in Medicine and Biological Scienes, METMBS '03","author":"Aliferis","year":"2003"},{"key":"2023012512450837500_B3","article-title":"How to infer gene networks from expression profiles","volume":"3","author":"Bansal","year":"2007","journal-title":"Mol. 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