Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes

Title: Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes
Author(s): Lees, JA
Vehkala, M
Välimäki, N
Harris, SR
Chewapreecha, C
Croucher, NJ
Marttinen, P
Davies, MR
Steer, AC
Tong, SY
Honkela, A
Parkhill, J
Bentley, SD
Corander, J
Item Type: Journal Article
Abstract: Bacterial genomes vary extensively in terms of both gene content and gene sequence. This plasticity hampers the use of traditional SNP-based methods for identifying all genetic associations with phenotypic variation. Here we introduce a computationally scalable and widely applicable statistical method (SEER) for the identification of sequence elements that are significantly enriched in a phenotype of interest. SEER is applicable to tens of thousands of genomes by counting variable-length k-mers using a distributed string-mining algorithm. Robust options are provided for association analysis that also correct for the clonal population structure of bacteria. Using large collections of genomes of the major human pathogens Streptococcus pneumoniae and Streptococcus pyogenes, SEER identifies relevant previously characterized resistance determinants for several antibiotics and discovers potential novel factors related to the invasiveness of S. pyogenes. We thus demonstrate that our method can answer important biologically and medically relevant questions.
Publication Date: 16-Sep-2016
Date of Acceptance: 28-Jul-2016
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 7
Copyright Statement: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 104169/Z/14/Z
Keywords: MD Multidisciplinary
Publication Status: Published
Article Number: 12797
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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