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A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes

Please always quote using this URN: urn:nbn:de:bvb:20-opus-186502
  • Motivation: Next generation sequencing technologies have provided us with a wealth of information on genetic variation, but predi cting 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. Results: We present a hidden Markov model based approach we callMotivation: Next generation sequencing technologies have provided us with a wealth of information on genetic variation, but predi cting 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. 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.show moreshow less

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Metadaten
Author: Nicole E. Wheeler, Lars Barquist, Robert A. Kingsley, Paul P. Gardner
URN:urn:nbn:de:bvb:20-opus-186502
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Language:English
Parent Title (English):Bioinformatics
Year of Completion:2016
Volume:32
Issue:23
Pagenumber:3566-3574
Source:Bioinformatics (2016) 32:23, 3566-3574. https://doi.org/10.1093/bioinformatics/btw518
DOI:https://doi.org/10.1093/bioinformatics/btw518
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Cystic-fibriosis; Host adaptation; Pathogenicity; Rapid evolution; Salmonella-enteritidis; Sequence identity; Strains; Typhimurium; Variants; Yersinia
Release Date:2020/05/20
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International