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However, current methods to infer binding sites, such as simple thresholding based on p-values, are not optimal for a number of study objectives like combinatorial regulation, leading to potential loss of information. Hence, there is a need to develop more efficient statistical methods for analyzing such data.<\/jats:p><jats:p>Results: We propose to use log-linear models to study cooperative binding among transcription factors and have developed an Expectation-Maximization algorithm for statistical inferences. Our method is advantageous over simple thresholding methods both based on simulation and real data studies. We apply our method to infer the cooperative network of 204 regulators in Rich Medium and a subset of them in four different environmental conditions. Our results indicate that the cooperative network is condition specific; for a set of regulators, the network structure changes under different environmental conditions.<\/jats:p><jats:p>Availability: Our program is available at http:\/\/bioinformatics.med.yale.edu\/TFcooperativity<\/jats:p><jats:p>Contact: \u00a0hongyu.zhao@yale.edu<\/jats:p><jats:p>Supplementary information: Supplementary information is available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm523","type":"journal-article","created":{"date-parts":[[2007,11,8]],"date-time":"2007-11-08T01:26:33Z","timestamp":1194485193000},"page":"545-552","source":"Crossref","is-referenced-by-count":21,"title":["Statistical methods to infer cooperative binding among transcription factors in<i>Saccharomyces cerevisiae<\/i>"],"prefix":"10.1093","volume":"24","author":[{"given":"Debayan","family":"Datta","sequence":"first","affiliation":[{"name":"1 Department of Biomedical Engineering, Department of Epidemiology and Public Health and 3Department of Genetics, Yale University, New Haven, CT 06520, USA"}]},{"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"1 Department of Biomedical Engineering, Department of Epidemiology and Public Health and 3Department of Genetics, Yale University, New Haven, CT 06520, USA"},{"name":"1 Department of Biomedical Engineering, Department of Epidemiology and Public Health and 3Department of Genetics, Yale University, New Haven, CT 06520, USA"}]}],"member":"286","published-online":{"date-parts":[[2007,11,7]]},"reference":[{"key":"2023020209505556800_B1","doi-asserted-by":"crossref","first-page":"15344","DOI":"10.1016\/S0021-9258(17)36612-7","article-title":"Ino2 and Ino4 gene products, positive regulators of phospholipid biosynthesis in Saccharomyces cerevisiae, form a complex that binds to the Ino1 promoter","volume":"269","author":"Ambroziak","year":"1994","journal-title":"J. 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