{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:14:53Z","timestamp":1764688493165},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: \u2018Phylogenetic footprinting\u2019 is a widely applied approach to identify regulatory regions and potential transcription factor binding sites (TFBSs) using alignments of non-coding orthologous regions from two or more organisms. A systematic evaluation of its validity and usability based on known TFBSs is needed to use phylogenetic footprinting most effectively in the identification of unknown TFBSs.<\/jats:p>\n               <jats:p>Results: In this paper we use 2678 human, mouse and rat TFBSs from the TRANSFAC\u00ae database for this evaluation. To ensure the retrieval of correct orthologous sequences, we combine gene annotation and sequence homology searches. Demanding a sequence identity of at least 65% is most effective in discriminating TFBSs from non-functional sequence parts, while different alignment algorithms only have a minor influence on TFBS identification by human\u2013rodent comparisons. With this threshold \u223c72% of the known TFBSs are found conserved, a number which varies significantly between different transcription factors and also depends on the function of the regulated gene. TFBSs for certain transcription factors do not require strict sequence conservation but instead may show a high pattern conservation, limiting somewhat the validity of purely sequence-based phylogenetic footprinting.<\/jats:p>\n               <jats:p>Availability: Scripts are available from the authors upon request.<\/jats:p>\n               <jats:p>Contact: \u00a0tsa@bioinf.med.uni-goettingen.de<\/jats:p>\n               <jats:p>Supplementary information: \u00a0<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti819","type":"journal-article","created":{"date-parts":[[2005,12,7]],"date-time":"2005-12-07T03:03:48Z","timestamp":1133924628000},"page":"430-437","source":"Crossref","is-referenced-by-count":24,"title":["Evaluating phylogenetic footprinting for human\u2013rodent comparisons"],"prefix":"10.1093","volume":"22","author":[{"given":"Tilman","family":"Sauer","sequence":"first","affiliation":[{"name":"Department of Bioinformatics, UKG, Georg-August-University of Goettingen 1 \u00a0 1 \u00a0 \u00a0 Goldschmidtstrasse 1, 37077 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Shelest","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, UKG, Georg-August-University of Goettingen 1 \u00a0 1 \u00a0 \u00a0 Goldschmidtstrasse 1, 37077 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar","family":"Wingender","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, UKG, Georg-August-University of Goettingen 1 \u00a0 1 \u00a0 \u00a0 Goldschmidtstrasse 1, 37077 Goettingen, Germany"},{"name":"BIOBASE GmbH, Halchtersche Strasse 2 \u00a0 2 \u00a0 \u00a0 33, 38304 Wolfenbuettel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,12,6]]},"reference":[{"key":"2023012408505999800_b1","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1093\/bioinformatics\/16.11.1040","article-title":"MaskerAid: a performance enhancement to RepeatMasker","volume":"16","author":"Bedell","year":"2000","journal-title":"Bioinformatics"},{"key":"2023012408505999800_b2","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1126\/science.1098119","article-title":"Ultraconserved elements in the human genome","volume":"304","author":"Bejerano","year":"2004","journal-title":"Science"},{"key":"2023012408505999800_b3","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1101\/gr.1642804","article-title":"CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprinting","volume":"14","author":"Berezikov","year":"2004","journal-title":"Genome Res."},{"key":"2023012408505999800_b4","doi-asserted-by":"crossref","first-page":"RESEARCH0086.1","DOI":"10.1186\/gb-2002-3-12-research0086","article-title":"Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome","volume":"3","author":"Bergman","year":"2002","journal-title":"Genome Biol."},{"key":"2023012408505999800_b5","doi-asserted-by":"crossref","first-page":"R61","DOI":"10.1186\/gb-2004-5-9-r61","article-title":"Computational identification of developmental enhancers: conservation and function of transcription factor binding-site clusters in Drosophila melanogaster and Drosophila pseudoobscura","volume":"5","author":"Berman","year":"2004","journal-title":"Genome Biol."},{"key":"2023012408505999800_b6","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1101\/gr.789803","article-title":"AVID: A global alignment program","volume":"13","author":"Bray","year":"2003","journal-title":"Genome Res."},{"key":"2023012408505999800_b7","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1101\/gr.926603","article-title":"LAGAN and Multi-LAGAN: efficient tools for large-scale multiple alignment of genomic DNA","volume":"13","author":"Brudno","year":"2003","journal-title":"Genome Res."},{"key":"2023012408505999800_b8","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/gb-2003-5-1-201","article-title":"Computational prediction of transcription-factor binding site locations","volume":"5","author":"Bulyk","year":"2003","journal-title":"Genome Biol."},{"key":"2023012408505999800_b9","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.gde.2003.10.001","article-title":"Genomic regulatory regions: insights from comparative sequence analysis","volume":"13","author":"Cooper","year":"2003","journal-title":"Curr. 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