{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T02:25:47Z","timestamp":1722738347962},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Uncovering mechanisms underlying gene expression control is crucial to understand complex cellular responses. Studies in gene regulation often aim to identify regulatory players involved in a biological process of interest, either transcription factors coregulating a set of target genes or genes eventually controlled by a set of regulators. These are frequently prioritized with respect to a context-specific relevance score. Current approaches rely on relevance measures accounting exclusively for direct transcription factor\u2013target interactions, namely overrepresentation of binding sites or target ratios. Gene regulation has, however, intricate behavior with overlapping, indirect effect that should not be neglected. In addition, the rapid accumulation of regulatory data already enables the prediction of large-scale networks suitable for higher level exploration by methods based on graph theory. A paradigm shift is thus emerging, where isolated and constrained analyses will likely be replaced by whole-network, systemic-aware strategies.<\/jats:p>\n               <jats:p>Results: We present TFRank, a graph-based framework to prioritize regulatory players involved in transcriptional responses within the regulatory network of an organism, whereby every regulatory path containing genes of interest is explored and incorporated into the analysis. TFRank selected important regulators of yeast adaptation to stress induced by quinine and acetic acid, which were missed by a direct effect approach. Notably, they reportedly confer resistance toward the chemicals. In a preliminary study in human, TFRank unveiled regulators involved in breast tumor growth and metastasis when applied to genes whose expression signatures correlated with short interval to metastasis.<\/jats:p>\n               <jats:p>Availability: Prototype at http:\/\/kdbio.inesc-id.pt\/software\/tfrank\/.<\/jats:p>\n               <jats:p>Contact: \u00a0jpg@kdbio.inesc-id.pt; sara.madeira@ist.utl.pt;<\/jats:p>\n               <jats:p>Supplementary Information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr546","type":"journal-article","created":{"date-parts":[[2011,9,30]],"date-time":"2011-09-30T10:29:20Z","timestamp":1317378560000},"page":"3149-3157","source":"Crossref","is-referenced-by-count":17,"title":["TFRank: network-based prioritization of regulatory associations underlying transcriptional responses"],"prefix":"10.1093","volume":"27","author":[{"given":"Joana P.","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"},{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"}]},{"given":"Alexandre P.","family":"Francisco","sequence":"additional","affiliation":[{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"},{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"}]},{"given":"Nuno P.","family":"Mira","sequence":"additional","affiliation":[{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"},{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"}]},{"given":"Miguel C.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"},{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"}]},{"given":"Isabel","family":"S\u00e1-Correia","sequence":"additional","affiliation":[{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"},{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"}]},{"given":"Arlindo L.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"},{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"}]},{"given":"Sara C.","family":"Madeira","sequence":"additional","affiliation":[{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"},{"name":"1 Knowledge Discovery and Bioinformatics group, INESC\u2212ID, 2Department of Computer Science and Engineering, Instituto Superior T\u00e9cnico (IST), Technical University of Lisbon, 3Institute for Biotechnology and Bioengineering, IST, Technical University of Lisbon and 4Department of Bioengineering, IST, Technical University of Lisbon, Lisbon, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2011,9,29]]},"reference":[{"key":"2023012511332956900_B1","doi-asserted-by":"crossref","first-page":"D136","DOI":"10.1093\/nar\/gkq964","article-title":"YEASTRACT: providing a programmatic access to curated transcriptional 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