{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T05:27:18Z","timestamp":1735968438324,"version":"3.32.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HG000249"],"award-info":[{"award-number":["HG000249"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Quant. Biol."],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>Transcription factors (TFs) are major modulators of transcription and subsequent cellular processes. The binding of TFs to specific regulatory elements is governed by their specificity. Considering the gap between known TFs sequence and specificity, specificity prediction frameworks are highly desired. Key inputs to such frameworks are protein residues that modulate the specificity of TF under consideration. Simple measures like mutual information (MI) to delineate specificity influencing residues (SIRs) from alignment fail due to structural constraints imposed by the three\u2010dimensional structure of protein. Structural restraints on the evolution of the amino\u2010acid sequence lead to identification of false SIRs. In this manuscript we extended three methods (direct information, PSICOV and adjusted mutual information) that have been used to disentangle spurious indirect protein residue\u2010residue contacts from direct contacts, to identify SIRs from joint alignments of amino\u2010acids and specificity. We predicted SIRs for homeodomain (HD), helix\u2010loop\u2010helix, LacI and GntR families of TFs using these methods and compared to MI. Using various measures, we show that the performance of these three methods is comparable but better than MI. Implication of these methods in specificity prediction framework is discussed. The methods are implemented as an R package and available along with the alignments at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/stormo.wustl.edu\/SpecPred\">http:\/\/stormo.wustl.edu\/SpecPred<\/jats:ext-link>.<\/jats:p>","DOI":"10.1007\/s40484-015-0045-y","type":"journal-article","created":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T15:17:26Z","timestamp":1434467846000},"page":"115-123","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Determination of specificity influencing residues for key transcription factor families"],"prefix":"10.1002","volume":"3","author":[{"given":"Ronak Y.","family":"Patel","sequence":"first","affiliation":[{"name":"<!--1--> Department of Genetics School of Medicine Washington University St. Louis MO 63108 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Garde","sequence":"additional","affiliation":[{"name":"<!--2--> Center for Biological Sequence Analysis Department of Systems Biology Technical University of Denmark Kgs. Lyngby DK 2800 Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary D.","family":"Stormo","sequence":"additional","affiliation":[{"name":"<!--1--> Department of Genetics School of Medicine Washington University St. Louis MO 63108 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,11]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.169508.113"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235587"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20140295"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2701"},{"key":"e_1_2_6_6_2","first-page":"126","article-title":"Leveraging transcription factors to speed cellobiose fermentation by Saccharomyces cerevisiae","volume":"7","author":"Lin Y.","year":"2014","journal-title":"Biotechnol. Biofuels"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.136838.111"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.150904.112"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2538"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/335294a0"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20102836(02)00917\u20108"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku132"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0010001"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn331"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn580"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt890"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.29.1.183"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts202"},{"volume-title":"Introduction to protein\u2010DNA interactions: structure, thermodynamics, and bioinformatics","year":"2013","author":"Stormo G. D.","key":"e_1_2_6_19_2"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.59.4983"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1214\/lnms\/1215455556"},{"key":"e_1_2_6_22_2","article-title":"Using sequence alignments to predict protein structure and stability with high accuracy","author":"Lapedes A.","year":"2002","journal-title":"q\u2010bio. <?Pub Caret?>QM, arXiv:1207.2484"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003176"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr638"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1314045110"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028766"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111471108"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805923106"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb4100203"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02030"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2635"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq858"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq992"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.12.009"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201014\u2010745"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bar009"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp919"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002195"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1223"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg329"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505147102"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm272"},{"key":"e_1_2_6_43_2","article-title":"A regression\u2010 based interpretation of the inverse of thesample covariance matrix","author":"Kwan C.","year":"2014","journal-title":"Spreadsheets in Education (eJSiE): 7, Article 3."},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm604"}],"container-title":["Quantitative Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40484-015-0045-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40484-015-0045-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s40484-015-0045-y","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T09:57:44Z","timestamp":1735898264000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s40484-015-0045-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1007\/s40484-015-0045-y"],"URL":"https:\/\/doi.org\/10.1007\/s40484-015-0045-y","archive":["Portico"],"relation":{},"ISSN":["2095-4689","2095-4697"],"issn-type":[{"type":"print","value":"2095-4689"},{"type":"electronic","value":"2095-4697"}],"subject":[],"published":{"date-parts":[[2015,11]]}}}