{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:42Z","timestamp":1772138082102,"version":"3.50.1"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T00:00:00Z","timestamp":1479254400000},"content-version":"vor","delay-in-days":100,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["WT098051"],"award-info":[{"award-number":["WT098051"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"PhD scholarship from the University of Canterbury"},{"name":"a Research Fellowship from the Alexander von Humboldt Stiftung\/Foundation"},{"name":"a Rutherford Discovery Fellowship administered by the Royal Society of New Zealand"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Motivation: Next generation sequencing technologies have provided us with a wealth of information on genetic variation, but predicting the functional significance of this variation is a difficult task. While many comparative genomics studies have focused on gene flux and large scale changes, relatively little attention has been paid to quantifying the effects of single nucleotide polymorphisms and indels on protein function, particularly in bacterial genomics.<\/jats:p>\n                  <jats:p>Results: We present a hidden Markov model based approach we call delta-bitscore (DBS) for identifying orthologous proteins that have diverged at the amino acid sequence level in a way that is likely to impact biological function. We benchmark this approach with several widely used datasets and apply it to a proof-of-concept study of orthologous proteomes in an investigation of host adaptation in Salmonella enterica. We highlight the value of the method in identifying functional divergence of genes, and suggest that this tool may be a better approach than the commonly used dN\/dS metric for identifying functionally significant genetic changes occurring in recently diverged organisms.<\/jats:p>\n                  <jats:p>Availability and Implementation: A program implementing DBS for pairwise genome comparisons is freely available at: https:\/\/github.com\/UCanCompBio\/deltaBS.<\/jats:p>\n                  <jats:p>Contact: \u00a0nicole.wheeler@pg.canterbury.ac.nz or lars.barquist@uni-wuerzburg.de<\/jats:p>\n                  <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw518","type":"journal-article","created":{"date-parts":[[2016,8,8]],"date-time":"2016-08-08T21:43:59Z","timestamp":1470692639000},"page":"3566-3574","source":"Crossref","is-referenced-by-count":29,"title":["A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes"],"prefix":"10.1093","volume":"32","author":[{"given":"Nicole E.","family":"Wheeler","sequence":"first","affiliation":[{"name":"1School of Biological Sciences, University of Canterbury, Christchurch, New Zealand,"},{"name":"2Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand,"}]},{"given":"Lars","family":"Barquist","sequence":"additional","affiliation":[{"name":"3Institute for Molecular Infection Biology, University of Wuerzburg, Wuerzburg, Germany,"}]},{"given":"Robert A.","family":"Kingsley","sequence":"additional","affiliation":[{"name":"4Institute of Food Research, Norwich Research Park, Norwich, UK,"},{"name":"5Wellcome Trust Sanger Institute, Hinxton, UK"}]},{"given":"Paul P.","family":"Gardner","sequence":"additional","affiliation":[{"name":"1School of Biological Sciences, University of Canterbury, Christchurch, New Zealand,"},{"name":"2Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand,"},{"name":"6Bio-protection Research Centre, University of Canterbury, Christchurch, New Zealand"}]}],"member":"286","published-online":{"date-parts":[[2016,8,8]]},"reference":[{"key":"2023020114074314600_btw518-B1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jmb.2008.12.045","article-title":"Domain-based and family-specific sequence identity thresholds increase the levels of reliable protein function transfer","volume":"387","author":"Addou","year":"2009","journal-title":"J. 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