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Bioinformatics
Year: 2009  |  Volume: 25  |  Issue: 16  |  Page No.: 2074 - 2075

Detecting SNPs and estimating allele frequencies in clonal bacterial populations by sequencing pooled DNA

K. E Holt, Y. Y Teo, H Li, S Nair, G Dougan, J Wain and J. Parkhill    

Abstract:

Summary: Here, we present a method for estimating the frequencies of SNP alleles present within pooled samples of DNA using high-throughput short-read sequencing. The method was tested on real data from six strains of the highly monomorphic pathogen Salmonella Paratyphi A, sequenced individually and in a pool. A variety of read mapping and quality-weighting procedures were tested to determine the optimal parameters, which afforded ≥80% sensitivity of SNP detection and strong correlation with true SNP frequency at poolwide read depth of 40x, declining only slightly at read depths 20–40x.

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