{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:27:06Z","timestamp":1761895626642},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Gene Ontology (GO) enrichment analysis remains one of the most common methods for hypothesis generation from high throughput datasets. However, we believe that researchers strive to test other hypotheses that fall outside of GO. Here, we developed and evaluated a tool for hypothesis generation from gene or protein lists using ontological concepts present in manually curated text that describes those genes and proteins.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>As a consequence we have developed the method Statistical Tracking of Ontological Phrases (STOP) that expands the realm of testable hypotheses in gene set enrichment analyses by integrating automated annotations of genes to terms from over 200 biomedical ontologies. While not as precise as manually curated terms, we find that the additional enriched concepts have value when coupled with traditional enrichment analyses using curated terms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Multiple ontologies have been developed for gene and protein annotation, by using a dataset of both manually curated GO terms and automatically recognized concepts from curated text we can expand the realm of hypotheses that can be discovered. The web application STOP is available at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mooneygroup.org\/stop\/\" ext-link-type=\"uri\">http:\/\/mooneygroup.org\/stop\/<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-14-53","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T19:14:28Z","timestamp":1360869268000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["STOP using just GO: a multi-ontology hypothesis generation tool for high throughput experimentation"],"prefix":"10.1186","volume":"14","author":[{"given":"Tobias","family":"Wittkop","sequence":"first","affiliation":[]},{"given":"Emily","family":"TerAvest","sequence":"additional","affiliation":[]},{"given":"Uday S","family":"Evani","sequence":"additional","affiliation":[]},{"given":"K Mathew","family":"Fleisch","sequence":"additional","affiliation":[]},{"given":"Ari E","family":"Berman","sequence":"additional","affiliation":[]},{"given":"Corey","family":"Powell","sequence":"additional","affiliation":[]},{"given":"Nigam H","family":"Shah","sequence":"additional","affiliation":[]},{"given":"Sean D","family":"Mooney","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,2,14]]},"reference":[{"key":"5830_CR1","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005, 102: 15545-15550. 10.1073\/pnas.0506580102.","journal-title":"Proc Natl Acad Sci USA"},{"key":"5830_CR2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000, 25: 25-29. 10.1038\/75556.","journal-title":"Nat Genet"},{"key":"5830_CR3","doi-asserted-by":"publisher","first-page":"D262","DOI":"10.1093\/nar\/gkh021","volume":"32","author":"E Camon","year":"2004","unstructured":"Camon E, Magrane M, Barrell D, Lee V, Dimmer E, Maslen J, Binns D, Harte N, Lopez R, Apweiler R: The Gene Ontology Annotation (GOA) Database: sharing knowledge in Uniprot with Gene Ontology. Nucleic Acids Res. 2004, 32: D262-D266. 10.1093\/nar\/gkh021.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR4","doi-asserted-by":"publisher","first-page":"3448","DOI":"10.1093\/bioinformatics\/bti551","volume":"21","author":"S Maere","year":"2005","unstructured":"Maere S, Heymans K, Kuiper M: BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 2005, 21: 3448-3449. 10.1093\/bioinformatics\/bti551.","journal-title":"Bioinformatics"},{"key":"5830_CR5","doi-asserted-by":"publisher","first-page":"W358","DOI":"10.1093\/nar\/gkn276","volume":"36","author":"Q Zheng","year":"2008","unstructured":"Zheng Q, Wang XJ: GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis. Nucleic Acids Res. 2008, 36: W358-W363. 10.1093\/nar\/gkn276.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR6","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","volume":"25","author":"G Bindea","year":"2009","unstructured":"Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, Galon J: ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009, 25: 1091-1093. 10.1093\/bioinformatics\/btp101.","journal-title":"Bioinformatics"},{"key":"5830_CR7","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1186\/1471-2105-8-426","volume":"8","author":"BT Sherman","year":"2007","unstructured":"Sherman BT, da Huang W, Tan Q, Guo Y, Bour S, Liu D, Stephens R, Baseler MW, Lane HC, Lempicki RA: DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinforma. 2007, 8: 426-10.1186\/1471-2105-8-426.","journal-title":"BMC Bioinforma"},{"key":"5830_CR8","doi-asserted-by":"publisher","first-page":"D1067","DOI":"10.1093\/nar\/gkr968","volume":"40","author":"EJ Baker","year":"2012","unstructured":"Baker EJ, Jay JJ, Bubier JA, Langston MA, Chesler EJ: GeneWeaver: a web-based system for integrative functional genomics. Nucleic Acids Res. 2012, 40: D1067-D1076. 10.1093\/nar\/gkr968.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR9","doi-asserted-by":"publisher","first-page":"i41","DOI":"10.1093\/bioinformatics\/btm229","volume":"23","author":"WA Baumgartner Jr","year":"2007","unstructured":"Baumgartner WA, Cohen KB, Fox LM, Acquaah-Mensah G, Hunter L: Manual curation is not sufficient for annotation of genomic databases. Bioinformatics. 2007, 23: i41-i48. 10.1093\/bioinformatics\/btm229.","journal-title":"Bioinformatics"},{"key":"5830_CR10","doi-asserted-by":"publisher","first-page":"D52","DOI":"10.1093\/nar\/gkq1237","volume":"39","author":"D Maglott","year":"2011","unstructured":"Maglott D, Ostell J, Pruitt KD, Tatusova T: Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res. 2011, 39: D52-D57. 10.1093\/nar\/gkq1237.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR11","doi-asserted-by":"publisher","first-page":"D115","DOI":"10.1093\/nar\/gkh131","volume":"32","author":"R Apweiler","year":"2004","unstructured":"Apweiler R, Bairoch A, Wu CH, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M: UniProt: the Universal Protein knowledgebase. Nucleic Acids Res. 2004, 32: D115-D119. 10.1093\/nar\/gkh131.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR12","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1089\/omi.2006.10.185","volume":"10","author":"DL Rubin","year":"2006","unstructured":"Rubin DL, Lewis SE, Mungall CJ, Misra S, Westerfield M, Ashburner M, Sim I, Chute CG, Solbrig H, Storey MA: National Center for Biomedical Ontology: advancing biomedicine through structured organization of scientific knowledge. OMICS. 2006, 10: 185-198. 10.1089\/omi.2006.10.185.","journal-title":"OMICS"},{"key":"5830_CR13","doi-asserted-by":"publisher","first-page":"W541","DOI":"10.1093\/nar\/gkr469","volume":"39","author":"PL Whetzel","year":"2011","unstructured":"Whetzel PL, Noy NF, Shah NH, Alexander PR, Nyulas C, Tudorache T, Musen MA: BioPortal: enhanced functionality via new Web services from the National Center for Biomedical Ontology to access and use ontologies in software applications. Nucleic Acids Res. 2011, 39: W541-W545. 10.1093\/nar\/gkr469.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR14","doi-asserted-by":"publisher","first-page":"W155","DOI":"10.1093\/nar\/gkq331","volume":"38","author":"R Cote","year":"2010","unstructured":"Cote R, Reisinger F, Martens L, Barsnes H, Vizcaino JA, Hermjakob H: The Ontology Lookup Service: bigger and better. Nucleic Acids Res. 2010, 38: W155-W160. 10.1093\/nar\/gkq331.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/1471-2105-7-97","volume":"7","author":"RG Cote","year":"2006","unstructured":"Cote RG, Jones P, Apweiler R, Hermjakob H: The Ontology Lookup Service, a lightweight cross-platform tool for controlled vocabulary queries. BMC Bioinforma. 2006, 7: 97-10.1186\/1471-2105-7-97.","journal-title":"BMC Bioinforma"},{"key":"5830_CR16","volume-title":"AMIA Summit on Translational Bioinformatics","author":"C Jonquet","year":"2009","unstructured":"Jonquet C, Shah NH, Musen MA: The Open Biomedical Annotator. AMIA Summit on Translational Bioinformatics. 2009, San Francisco"},{"key":"5830_CR17","doi-asserted-by":"publisher","first-page":"D793","DOI":"10.1093\/nar\/gkn665","volume":"37","author":"J Amberger","year":"2009","unstructured":"Amberger J, Bocchini CA, Scott AF, Hamosh A: McKusick\u2019s Online Mendelian Inheritance in Man (OMIM). Nucleic Acids Res. 2009, 37: D793-D796. 10.1093\/nar\/gkn665.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR18","first-page":"797","volume":"2010","author":"R Tirrell","year":"2010","unstructured":"Tirrell R, Evani U, Berman AE, Mooney SD, Musen MA, Shah NH: An ontology-neutral framework for enrichment analysis. AMIA Annual Symposium proceedings \/ AMIA Symposium AMIA Symposium. 2010, 2010: 797-801.","journal-title":"AMIA Annual Symposium proceedings \/ AMIA Symposium AMIA Symposium"},{"key":"5830_CR19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jbi.2006.02.013","volume":"40","author":"N Sioutos","year":"2007","unstructured":"Sioutos N, de Coronado S, Haber MW, Hartel FW, Shaiu WL, Wright LW: NCI Thesaurus: a semantic model integrating cancer-related clinical and molecular information. J Biomed Inform. 2007, 40: 30-43. 10.1016\/j.jbi.2006.02.013.","journal-title":"J Biomed Inform"},{"issue":"Suppl 1","key":"5830_CR20","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1186\/1471-2164-10-S1-S6","volume":"10","author":"JD Osborne","year":"2009","unstructured":"Osborne JD, Flatow J, Holko M, Lin SM, Kibbe WA, Zhu LJ, Danila MI, Feng G, Chisholm RL: Annotating the human genome with Disease Ontology. BMC Genomics. 2009, 10 (Suppl 1): S6-10.1186\/1471-2164-10-S1-S6.","journal-title":"BMC Genomics"},{"key":"5830_CR21","doi-asserted-by":"publisher","first-page":"D744","DOI":"10.1093\/nar\/gkn842","volume":"37","author":"MR Dwinell","year":"2009","unstructured":"Dwinell MR, Worthey EA, Shimoyama M, Bakir-Gungor B, DePons J, Laulederkind S, Lowry T, Nigram R, Petri V, Smith J, Stoddard A, Twigger SN, Jacob HJ, RGD Team: The Rat Genome Database 2009: variation, ontologies and pathways. Nucleic Acids Res. 2009, 37: D744-D749. 10.1093\/nar\/gkn842.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR22","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1111\/j.1399-0004.2010.01436.x","volume":"77","author":"PN Robinson","year":"2010","unstructured":"Robinson PN, Mundlos S: The human phenotype ontology. Clin Genet. 2010, 77: 525-534. 10.1111\/j.1399-0004.2010.01436.x.","journal-title":"Clin Genet"},{"key":"5830_CR23","doi-asserted-by":"publisher","first-page":"D396","DOI":"10.1093\/nar\/gkn803","volume":"37","author":"D Barrell","year":"2009","unstructured":"Barrell D, Dimmer E, Huntley RP, Binns D, O\u2019Donovan C, Apweiler R: The GOA database in 2009-an integrated Gene Ontology Annotation resource. Nucleic Acids Res. 2009, 37: D396-D403. 10.1093\/nar\/gkn803.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR24","doi-asserted-by":"publisher","first-page":"D555","DOI":"10.1093\/nar\/gkn788","volume":"37","author":"S Tweedie","year":"2009","unstructured":"Tweedie S, Ashburner M, Falls K, Leyland P, McQuilton P, Marygold S, Millburn G, Osumi-Sutherland D, Schroeder A, Seal R, Zhang H: FlyBase: enhancing Drosophila Gene Ontology annotations. Nucleic Acids Res. 2009, 37: D555-D559. 10.1093\/nar\/gkn788.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR25","doi-asserted-by":"publisher","first-page":"D463","DOI":"10.1093\/nar\/gkp952","volume":"38","author":"TW Harris","year":"2010","unstructured":"Harris TW, Antoshechkin I, Bieri T, Blasiar D, Chan J, Chen WJ, De La Cruz N, Davis P, Duesbury M, Fang R: WormBase: a comprehensive resource for nematode research. Nucleic Acids Res. 2010, 38: D463-D467. 10.1093\/nar\/gkp952.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR26","doi-asserted-by":"publisher","first-page":"D744","DOI":"10.1093\/nar\/gkn842","volume":"37","author":"MR Dwinell","year":"2009","unstructured":"Dwinell MR, Worthey EA, Shimoyama M, Bakir-Gungor B, DePons J, Laulederkind S, Lowry T, Nigram R, Petri V, Smith J: The Rat Genome Database 2009: variation, ontologies and pathways. Nucleic Acids Res. 2009, 37: D744-D749. 10.1093\/nar\/gkn842.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR27","doi-asserted-by":"publisher","first-page":"D700","DOI":"10.1093\/nar\/gkr1029","volume":"40","author":"JM Cherry","year":"2012","unstructured":"Cherry JM, Hong EL, Amundsen C, Balakrishnan R, Binkley G, Chan ET, Christie KR, Costanzo MC, Dwight SS, Engel SR: Saccharomyces Genome Database: the genomics resource of budding yeast. Nucleic Acids Res. 2012, 40: D700-D705. 10.1093\/nar\/gkr1029.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR28","doi-asserted-by":"publisher","first-page":"D583","DOI":"10.1093\/nar\/gkq1143","volume":"39","author":"IM Keseler","year":"2011","unstructured":"Keseler IM, Collado-Vides J, Santos-Zavaleta A, Peralta-Gil M, Gama-Castro S, Muniz-Rascado L, Bonavides-Martinez C, Paley S, Krummenacker M, Altman T: EcoCyc: a comprehensive database of Escherichia coli biology. Nucleic Acids Res. 2011, 39: D583-D590. 10.1093\/nar\/gkq1143.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR29","doi-asserted-by":"publisher","first-page":"D842","DOI":"10.1093\/nar\/gkq1008","volume":"39","author":"JA Blake","year":"2011","unstructured":"Blake JA, Bult CJ, Kadin JA, Richardson JE, Eppig JT: The Mouse Genome Database (MGD): premier model organism resource for mammalian genomics and genetics. Nucleic Acids Res. 2011, 39: D842-D848. 10.1093\/nar\/gkq1008.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR30","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nsb919","volume":"10","author":"S Bencharit","year":"2003","unstructured":"Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR: Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Biol. 2003, 10: 349-356. 10.1038\/nsb919.","journal-title":"Nat Struct Biol"},{"key":"5830_CR31","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.devcel.2007.07.016","volume":"13","author":"CM Haynes","year":"2007","unstructured":"Haynes CM, Petrova K, Benedetti C, Yang Y, Ron D: ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans. Dev Cell. 2007, 13: 467-480. 10.1016\/j.devcel.2007.07.016.","journal-title":"Dev Cell"},{"key":"5830_CR32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/978-1-60761-232-2_6","volume":"577","author":"TS Prasad","year":"2009","unstructured":"Prasad TS, Kandasamy K, Pandey A: Human Protein Reference Database and Human Proteinpedia as discovery tools for systems biology. Methods Mol Biol. 2009, 577: 67-79. 10.1007\/978-1-60761-232-2_6.","journal-title":"Methods Mol Biol"},{"key":"5830_CR33","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1002\/prot.21989","volume":"72","author":"P Radivojac","year":"2008","unstructured":"Radivojac P, Peng K, Clark WT, Peters BJ, Mohan A, Boyle SM, Mooney SD: An integrated approach to inferring gene-disease associations in humans. Proteins. 2008, 72: 1030-1037. 10.1002\/prot.21989.","journal-title":"Proteins"},{"key":"5830_CR34","doi-asserted-by":"publisher","first-page":"D857","DOI":"10.1093\/nar\/gkr930","volume":"40","author":"L Licata","year":"2012","unstructured":"Licata L, Briganti L, Peluso D, Perfetto L, Iannuccelli M, Galeota E, Sacco F, Palma A, Nardozza AP, Santonico E: MINT, the molecular interaction database: 2012 update. Nucleic Acids Res. 2012, 40: D857-D861. 10.1093\/nar\/gkr930.","journal-title":"Nucleic Acids Res"},{"key":"5830_CR35","volume-title":"Statistical Methods for Research Workers","author":"RA Fisher","year":"1932","unstructured":"Fisher RA: Statistical Methods for Research Workers. 1932, London: Oliver and Boyd"},{"key":"5830_CR36","first-page":"3","volume":"81","author":"RJ Cabin","year":"2000","unstructured":"Cabin RJ, Mitchell RJ: To Bonferroni or Not to Bonferroni: When and How Are the Questions. Bull Ecol Soc Am. 2000, 81: 3-","journal-title":"Bull Ecol Soc Am"},{"key":"5830_CR37","first-page":"6","volume":"6","author":"S Holm","year":"1979","unstructured":"Holm S: A Simple Sequentially Rejective Multiple Test Procedure. Scand J Stat. 1979, 6: 6-","journal-title":"Scand J Stat"},{"key":"5830_CR38","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0166-4328(01)00297-2","volume":"125","author":"Y Benjamini","year":"2001","unstructured":"Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I: Controlling the false discovery rate in behavior genetics research. Behav Brain Res. 2001, 125: 279-284. 10.1016\/S0166-4328(01)00297-2.","journal-title":"Behav Brain Res"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-14-53.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T23:27:08Z","timestamp":1630538828000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-14-53"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,14]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["5830"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-14-53","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,14]]},"assertion":[{"value":"26 January 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"53"}}