TY  - JOUR
A1  - Wheeler, Nicole E.
A1  - Barquist, Lars
A1  - Kingsley, Robert A.
A1  - Gardner, Paul P.
T1  - A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes
JF  - Bioinformatics
N2  - 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 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.
KW  - Host adaptation
KW  - Salmonella-enteritidis
KW  - Sequence identity
KW  - Rapid evolution
KW  - Variants
KW  - Cystic-fibriosis
KW  - Strains
KW  - Pathogenicity
KW  - Typhimurium
KW  - Yersinia
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186502
VL  - 32
IS  - 23
ER  - 
TY  - JOUR
A1  - Okoro, Chinyere K.
A1  - Barquist, Lars
A1  - Connor, Thomas R.
A1  - Harris, Simon R.
A1  - Clare, Simon
A1  - Stevens, Mark P.
A1  - Arends, Mark J.
A1  - Hale, Christine
A1  - Kane, Leanne
A1  - Pickard, Derek J.
A1  - Hill, Jennifer
A1  - Harcourt, Katherine
A1  - Parkhill, Julian
A1  - Dougan, Gordon
A1  - Kingsley, Robert A.
T1  - Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa
JF  - PLoS Neglected Tropical Diseases
N2  - Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population.
KW  - genome sequence
KW  - infection
KW  - pathogenicity
KW  - children
KW  - disease
KW  - adults
KW  - identification
KW  - Escherichia coli
KW  - virulence
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143779
VL  - 9
IS  - 3
ER  -