title: A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes.
abstract: 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.
  
  
  
  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.
  
  
  
  A program implementing DBS for pairwise genome comparisons is freely available at: https://github.com/UCanCompBio/deltaBS CONTACT: nicole.wheeler@pg.canterbury.ac.nz or lars.barquist@uni-wuerzburg.deSupplementary information: Supplementary data are available at Bioinformatics online.
authors: School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.|Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand.
authors: Nicole E
authors: NE
authors: Wheeler
authors: Institute for Molecular Infection Biology, University of Wuerzburg, Wuerzburg, Germany.
authors: Lars
authors: L
authors: Barquist
authors: Institute of Food Research, Norwich Research Park, Norwich, UK.|Wellcome Trust Sanger Institute, Hinxton, UK.
authors: Robert A
authors: RA
authors: Kingsley
authors: School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.|Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand.|Bio-protection Research Centre, University of Canterbury, Christchurch, New Zealand.
authors: Paul P
authors: PP
authors: Gardner
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000235:genetics; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods*; D008390:Markov Chains; D008962:Models, Theoretical; D020543:Proteome; D019779:Salmonella enterica / Q000235:genetics; D012984:Software
chemical_list: D001426:Bacterial Proteins; D020543:Proteome