{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:28:45Z","timestamp":1790854125989,"version":"4.1.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: Hundreds of genes lacking homology to any protein of known function are sequenced every day. Genome-context methods have proved useful in providing clues about functional annotations for many proteins. However, genome-context methods detect many biological types of functional associations, and do not identify which type of functional association they have found.<\/jats:p>\n               <jats:p>Results: We have developed two new genome-context-based algorithms. Algorithm 1 extends our previous algorithm for identifying missing enzymes in predicted metabolic pathways (pathway holes) to use genome-context features. The new algorithm has significantly improved scope because it can now be applied to pathway reactions to which sequence similarity methods cannot be applied due to an absence of known sequences for enzymes catalyzing the reaction in other organisms. The new method identifies at least one known enzyme in the top ten hits for 58% of EcoCyc reactions that lack enzyme sequences in other organisms. Surprisingly, the addition of genome-context features does not improve the accuracy of the algorithm when sequences for the enzyme do exist in other organisms. Algorithm 2 uses genome-context methods to predict three distinct types of functional relationships between pairs of proteins: pairs that occur in the same protein complex, the same pathway, or the same operon. This algorithm performs with varying degrees of accuracy on each type of relationship, and performs best in predicting pathway and protein complex relationships.<\/jats:p>\n               <jats:p>Contact: pkarp@ai.sri.com<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm213","type":"journal-article","created":{"date-parts":[[2007,7,23]],"date-time":"2007-07-23T16:13:46Z","timestamp":1185207226000},"page":"i205-i211","source":"Crossref","is-referenced-by-count":24,"title":["Using genome-context data to identify specific types of functional associations in pathway\/genome databases"],"prefix":"10.1093","volume":"23","author":[{"given":"Michelle L.","family":"Green","sequence":"first","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Karp","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,7,1]]},"reference":[{"key":"2023062708514494300_B1","doi-asserted-by":"crossref","first-page":"D580","DOI":"10.1093\/nar\/gki006","article-title":"The Stanford microarray database accommodates additional microarray platforms and data formats","volume":"33","author":"Ball","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023062708514494300_B2","doi-asserted-by":"crossref","first-page":"D562","DOI":"10.1093\/nar\/gki022","article-title":"NCBI GEO: mining millions of expression profiles-database and tools","volume":"33","author":"Barrett","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023062708514494300_B3","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1186\/gb-2004-5-5-r35","article-title":"Prolinks: a database of protein functional linkages derived from coevolution","volume":"5","author":"Bowers","year":"2004","journal-title":"Genome Biol"},{"key":"2023062708514494300_B4","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/S0968-0004(98)01274-2","article-title":"Conservation of gene order: a fingerprint of proteins that physically interact","volume":"23","author":"Dandekar","year":"1998","journal-title":"Trends Biochem. Sci"},{"key":"2023062708514494300_B5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1089\/omi.1.1998.3.199","article-title":"Microbial genescapes: phyletic and functional patterns of ORF distribution among prokaryotes","volume":"3","author":"Gaasterland","year":"1998","journal-title":"Microb. Comp. Genomics"},{"key":"2023062708514494300_B6","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1471-2105-5-76","article-title":"A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases","volume":"5","author":"Green","year":"2004","journal-title":"BMC Bioinform"},{"key":"2023062708514494300_B7","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1093\/nar\/gkl438","article-title":"The outcomes of pathway database computations depend on pathway ontology","volume":"34","author":"Green","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2023062708514494300_B8","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1186\/gb-2004-5-8-401","article-title":"Call for an enzyme genomics initiative","volume":"5","author":"Karp","year":"2004","journal-title":"Genome Biol"},{"key":"2023062708514494300_B9","doi-asserted-by":"crossref","first-page":"6083","DOI":"10.1093\/nar\/gki892","article-title":"Expansion of the BioCyc collection of pathway\/genome databases to 160 genomes","volume":"33","author":"Karp","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023062708514494300_B10","doi-asserted-by":"crossref","first-page":"D334","DOI":"10.1093\/nar\/gki108","article-title":"EcoCyc: a comprehensive database resource for Escherichia coli","volume":"33","author":"Keseler","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023062708514494300_B11","doi-asserted-by":"crossref","first-page":"I178","DOI":"10.1093\/bioinformatics\/bth930","article-title":"Filling gaps in a metabolic network using expression information","volume":"20","author":"Kharchenko","year":"2004","journal-title":"Bioinformatics"},{"key":"2023062708514494300_B12","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/1471-2105-7-177","article-title":"Identifying metabolic enzymes with multiple types of association evidence","volume":"7","author":"Kharchenko","year":"2006","journal-title":"BMC Bioinform"},{"key":"2023062708514494300_B13","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1126\/science.285.5428.751","article-title":"Detecting protein function and protein-protein interactions from genome sequences","volume":"285","author":"Marcotte","year":"1999","journal-title":"Science"},{"key":"2023062708514494300_B14","first-page":"93","article-title":"Use of contiguity on the chromosome to predict functional coupling","volume":"1","author":"Overbeek","year":"1998","journal-title":"In Silico Biol"},{"key":"2023062708514494300_B15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1093\/bioinformatics\/18.5.715","article-title":"Evaluation of computational metabolic-pathway predictions for Helicobacter pylori","volume":"18","author":"Paley","year":"2002","journal-title":"Bioinformatics"},{"key":"2023062708514494300_B16","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1073\/pnas.96.8.4285","article-title":"Assigning protein functions by comparative genome analysis: protein phylogenetic profiles","volume":"96","author":"Pellegrini","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023062708514494300_B17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/jcb.10071","article-title":"Computational method to assign microbial genes to pathways","author":"Pellegrini","year":"2001","journal-title":"J. Cell Biochem"},{"key":"2023062708514494300_B18","doi-asserted-by":"crossref","DOI":"10.1109\/ICSENG.2005.47","article-title":"Identifying candidate genes using the BioWarehouse: a case study","volume-title":"18th International Conference on Systems Engineering (ICSEng '05)","author":"Pouliot","year":"2005"},{"key":"2023062708514494300_B19","doi-asserted-by":"crossref","first-page":"E42","DOI":"10.1371\/journal.pbio.0020042","article-title":"Identifying protein function\u2014A call for community action","author":"Roberts","year":"2004","journal-title":"PLOS Biol"},{"key":"2023062708514494300_B20","doi-asserted-by":"crossref","first-page":"D433","DOI":"10.1093\/nar\/gki005","article-title":"STRING: known and predicted protein-protein associations, integrated and transferred across organisms","volume":"33","author":"von Mering","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023062708514494300_B22","first-page":"research0064","article-title":"The society of genes: networks of functional links between genes from comparative genomics","author":"Yanai","year":"2002","journal-title":"Genome Biol"},{"key":"2023062708514494300_B21","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0168-9525(01)02621-X","article-title":"Identifying functional links between genes using conserved chromosomal proximity","volume":"18","author":"Yanai","year":"2002","journal-title":"Trends Genet"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/13\/i205\/50715293\/bioinformatics_23_13_i205.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/13\/i205\/50715293\/bioinformatics_23_13_i205.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T08:57:20Z","timestamp":1687856240000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/23\/13\/i205\/235310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7,1]]},"references-count":22,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2007,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btm213","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2007,7]]},"published":{"date-parts":[[2007,7,1]]}}}