RT Journal Article SR Electronic T1 A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes JF bioRxiv FD Cold Spring Harbor Laboratory SP 022616 DO 10.1101/022616 A1 Nicole E. Wheeler A1 Lars Barquist A1 Robert A. Kingsley A1 Paul P. Gardner YR 2016 UL http://biorxiv.org/content/early/2016/04/28/022616.abstract AB 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.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.Availability and Implementation A program implementing DBS for pairwise genome comparisons is freely available at: https://github.com/UCanCompBio/deltaBS.Contact nicole.wheeler{at}pg.canterbury.ac.nz