{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:56:26Z","timestamp":1773276986969,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Knowledge of the activation patterns of transcription factors (TFs) is fundamental to elucidate the dynamics of gene regulation in response to environmental conditions. Direct experimental measurement of TFs' activities is, however, challenging, resulting in a need to develop statistical tools to infer TF activities from mRNA expression levels of target genes. Current models, however, neglect important features of transcriptional regulation; in particular, the combinatorial nature of regulation, which is fundamental for signal integration, is not accounted for.<\/jats:p>\n               <jats:p>Results: We present a novel method to infer combinatorial regulation of gene expression by multiple transcription factors in large-scale transcriptional regulatory networks. The method implements a factorial hidden Markov model with a non-linear likelihood to represent the interactions between the hidden transcription factors. We explore our model's performance on artificial datasets and demonstrate the applicability of our method on genome-wide scale for three expression datasets. The results obtained using our model are biologically coherent and provide a tool to explore the concealed nature of combinatorial transcriptional regulation.<\/jats:p>\n               <jats:p>Availability: \u00a0http:\/\/homepages.inf.ed.ac.uk\/gsanguin\/software.html.<\/jats:p>\n               <jats:p>Contact: \u00a0g.sanguinetti@ed.ac.uk<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr113","type":"journal-article","created":{"date-parts":[[2011,3,3]],"date-time":"2011-03-03T02:00:16Z","timestamp":1299117616000},"page":"1277-1283","source":"Crossref","is-referenced-by-count":21,"title":["Large-scale learning of combinatorial transcriptional dynamics from gene expression"],"prefix":"10.1093","volume":"27","author":[{"given":"H. M. Shahzad","family":"Asif","sequence":"first","affiliation":[{"name":"1 School of Informatics, University of Edinburgh, 10 Crichton Street, Edinburgh EH8 9AB, UK and 2Department of Computer Science and Engineering, University of Engineering and Technology, Lahore, Pakistan"},{"name":"1 School of Informatics, University of Edinburgh, 10 Crichton Street, Edinburgh EH8 9AB, UK and 2Department of Computer Science and Engineering, University of Engineering and Technology, Lahore, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Sanguinetti","sequence":"additional","affiliation":[{"name":"1 School of Informatics, University of Edinburgh, 10 Crichton Street, Edinburgh EH8 9AB, UK and 2Department of Computer Science and Engineering, University of Engineering and Technology, Lahore, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,3,2]]},"reference":[{"key":"2023012512184412400_B1","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2006-7-3-r25","article-title":"Ranked prediction of p53 targets using hidden variable dynamical modelling","volume":"7","author":"Barenco","year":"2006","journal-title":"Genome Biol."},{"key":"2023012512184412400_B2","article-title":"Variational Algorithms for Approximate Bayesian Inference","volume-title":"UK PhD Thesis","author":"Beal","year":"2003"},{"key":"2023012512184412400_B3","doi-asserted-by":"crossref","first-page":"37612","DOI":"10.1074\/jbc.M206125200","article-title":"Mutations in the Pho2 (Bas2) transcription factor that differentially affect activation with its partner proteins Bas1, Pho4, and Swi5","volume":"277","author":"Bhoite","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2023012512184412400_B4","volume-title":"Pattern Recognition and Machine Learning.","author":"Bishop","year":"2006"},{"key":"2023012512184412400_B5","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1128\/MCB.16.3.847","article-title":"Gat1p, a GATA family protein whose production is sensitive to nitrogen catabolite repression, participates in transcriptional activation of nitrogen-catabolic genes in Saccharomyces cerevisiae","volume":"16","author":"Coffman","year":"1996","journal-title":"Mol. Cell. Biol."},{"key":"2023012512184412400_B6","doi-asserted-by":"crossref","first-page":"6746","DOI":"10.1073\/pnas.89.15.6746","article-title":"Coregulation of purine and histidine biosynthesis by the transcriptional activators BAS1 and BAS2","volume":"89","author":"Daignan-Fornier","year":"1992","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012512184412400_B7","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1074\/jbc.M808210200","article-title":"Carbon monoxide-releasing antibacterial molecules target respiration and global transcriptional regulators","volume":"284","author":"Davidge","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2023012512184412400_B8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1023\/A:1007425814087","article-title":"Factorial hidden Markov models","volume":"29","author":"Ghahramani","year":"1997","journal-title":"Mach. Learn."},{"key":"2023012512184412400_B9","first-page":"655","article-title":"The HAP3 regulatory locus of Saccharomyces cerevisiae encodes divergent overlapping transcripts","volume":"8","author":"Hahn","year":"1988","journal-title":"Mol. Cell. Biol."},{"key":"2023012512184412400_B10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature02800","article-title":"Transcriptional regulatory code of a eukaryotic genome","volume":"431","author":"Harbison","year":"2004","journal-title":"Nature"},{"key":"2023012512184412400_B11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1023\/A:1007665907178","article-title":"An introduction to variational methods for graphical models","volume":"37","author":"Jordan","year":"1999","journal-title":"Mach. Learn."},{"key":"2023012512184412400_B12","first-page":"785","article-title":"Modelling transcriptional regulation using Gaussian processes","volume-title":"Advances in Neural Information Processing Systems 19.","author":"Lawrence","year":"2006"},{"key":"2023012512184412400_B13","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1126\/science.1075090","article-title":"Transcriptional regulatory networks in Saccharomyces cerevisiae","volume":"298","author":"Lee","year":"2002","journal-title":"Science"},{"key":"2023012512184412400_B14","doi-asserted-by":"crossref","first-page":"15522","DOI":"10.1073\/pnas.2136632100","article-title":"Network component analysis: reconstruction of regulatory signals in biological systems","volume":"100","author":"Liao","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012512184412400_B15","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1093\/bioinformatics\/btq244","article-title":"Learning combinatorial transcriptional dynamics from gene expression data","volume":"26","author":"Opper","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012512184412400_B16","doi-asserted-by":"crossref","first-page":"11230","DOI":"10.1074\/jbc.M700728200","article-title":"Transition of Escherichia coli from aerobic to micro-aerobic conditions involves fast and slow reacting regulatory components","volume":"282","author":"Partridge","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2023012512184412400_B17","volume-title":"Genes & Signals.","author":"Ptashne","year":"2002"},{"key":"2023012512184412400_B18","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1471-2105-8-S2-S2","article-title":"Bayesian model-based inference of transcription factor activity","volume":"8","author":"Rogers","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2023012512184412400_B19","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1093\/bioinformatics\/btk017","article-title":"Bayesian sparse hidden components analysis for transcription regulation networks","volume":"22","author":"Sabatti","year":"2006","journal-title":"Bioinformatics"},{"key":"2023012512184412400_B20","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1093\/bioinformatics\/btl473","article-title":"Probabilistic inference of transcription factor concentrations and gene-specific regulatory activities","volume":"22","author":"Sanguinetti","year":"2006","journal-title":"Bioinformatics"},{"key":"2023012512184412400_B21","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1093\/bioinformatics\/btp138","article-title":"Switching regulatory models of cellular stress response","volume":"25","author":"Sanguinetti","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012512184412400_B22","doi-asserted-by":"crossref","first-page":"30886","DOI":"10.1074\/jbc.M005624200","article-title":"Roles of the Dal82p domains in allophanate\/oxalurate-dependent gene expression in Saccharomyces cerevisiae","volume":"275","author":"Scott","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2023012512184412400_B23","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1093\/bioinformatics\/btq469","article-title":"TFInfer: a tool for probabilistic inference of transcription factor activities","volume":"26","author":"Asif","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012512184412400_B24","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1089\/cmb.2009.0024","article-title":"A combined expression-interaction model for inferring the temporal activity of transcription factors","volume":"16","author":"Shi","year":"2009","journal-title":"J. Comput. Biol."},{"key":"2023012512184412400_B25","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1091\/mbc.9.12.3273","article-title":"Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization","volume":"9","author":"Spellman","year":"1998","journal-title":"Mol. Biol. Cell"},{"key":"2023012512184412400_B26","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1126\/science.1120499","article-title":"Logic of the yeast metabolic cycle: temporal compartmentalization of cellular processes","volume":"310","author":"Tu","year":"2005","journal-title":"Science"},{"key":"2023012512184412400_B27","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/bioinformatics\/btq104","article-title":"Reducing the algorithmic variability in transcriptome-based inference","volume":"26","author":"Tuna","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012512184412400_B28","doi-asserted-by":"crossref","first-page":"4647","DOI":"10.1002\/j.1460-2075.1993.tb06153.x","article-title":"Mutations in yeast HAP2\/HAP3 define a hybrid CCAAT box binding domain","volume":"12","author":"Xing","year":"1993","journal-title":"EMBO J."},{"key":"2023012512184412400_B29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/yea.1468","article-title":"Role of Gts1p in regulation of energy-metabolism oscillation in continuous cultures of the yeast Saccharomyces cerevisiae","volume":"24","author":"Xu","year":"2007","journal-title":"Yeast"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/27\/9\/1277\/48866726\/bioinformatics_27_9_1277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/27\/9\/1277\/48866726\/bioinformatics_27_9_1277.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T15:03:28Z","timestamp":1674659008000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/27\/9\/1277\/242347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,2]]},"references-count":29,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btr113","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2011,5,1]]},"published":{"date-parts":[[2011,3,2]]}}}