{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T14:29:47Z","timestamp":1759588187263},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2847,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Recognition of specific DNA sequences is a central mechanism by which transcription factors (TFs) control gene expression. Many TF-binding preferences, however, are unknown or poorly characterized, in part due to the difficulty associated with determining their specificity experimentally, and an incomplete understanding of the mechanisms governing sequence specificity. New techniques that estimate the affinity of TFs to all possible k-mers provide a new opportunity to study DNA\u2013protein interaction mechanisms, and may facilitate inference of binding preferences for members of a given TF family when such information is available for other family members.<\/jats:p>\n               <jats:p>Results: We employed a new dataset consisting of the relative preferences of mouse homeodomains for all eight-base DNA sequences in order to ask how well we can predict the binding profiles of homeodomains when only their protein sequences are given. We evaluated a panel of standard statistical inference techniques, as well as variations of the protein features considered. Nearest neighbour among functionally important residues emerged among the most effective methods. Our results underscore the complexity of TF\u2013DNA recognition, and suggest a rational approach for future analyses of TF families.<\/jats:p>\n               <jats:p>Contact: \u00a0t.hughes@utorotno.ca<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn645","type":"journal-article","created":{"date-parts":[[2008,12,17]],"date-time":"2008-12-17T03:38:42Z","timestamp":1229485122000},"page":"1012-1018","source":"Crossref","is-referenced-by-count":24,"title":["Predicting the binding preference of transcription factors to individual DNA <i>k<\/i>-mers"],"prefix":"10.1093","volume":"25","author":[{"given":"Trevis M.","family":"Alleyne","sequence":"first","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Pe\u00f1a-Castillo","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwenael","family":"Badis","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaheynoor","family":"Talukder","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael F.","family":"Berger","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Gehrke","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony A.","family":"Philippakis","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha L.","family":"Bulyk","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quaid D.","family":"Morris","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy R.","family":"Hughes","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Molecular Genetics, 2Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, 3Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, 4Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, 5Harvard\/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and 6Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,12,16]]},"reference":[{"key":"2023051607022105200_B1","doi-asserted-by":"crossref","first-page":"9187","DOI":"10.1021\/bi00197a022","article-title":"Differential DNA-binding specificity of the engrailed homeodomain: the role of residue 50","volume":"33","author":"Ades","year":"1994","journal-title":"Biochemistry"},{"key":"2023051607022105200_B2","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1093\/nar\/29.15.3258","article-title":"Molecular evolution of the homeodomain family of transcription factors","volume":"29","author":"Banerjee-Basu","year":"2001","journal-title":"Nucleic Acids 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