RT Journal Article SR Electronic T1 ISMapper: Identifying insertion sequences in bacterial genomes from short read sequence data JF bioRxiv FD Cold Spring Harbor Laboratory SP 016345 DO 10.1101/016345 A1 Jane Hawkey A1 Mohammad Hamidian A1 Ryan R. Wick A1 David J. Edwards A1 Helen Billman-Jacob A1 Ruth M. Hall A1 Kathryn E. Holt YR 2015 UL http://biorxiv.org/content/early/2015/03/10/016345.abstract AB Background Insertion sequences (IS) are small transposable elements, commonly found in bacterial genomes. Identifying the location of IS in bacterial genomes can be useful for a variety of purposes including epidemiological tracking and predicting antibiotic resistance. However IS are commonly present in multiple copies in a single genome, which complicates genome assembly and the identification of IS insertion sites. Here we present ISMapper, a mapping-based tool for identification of the site and orientation of IS insertions in bacterial genomes, direct from paired-end short read data.Results ISMapper was validated using three types of short read data: (i) simulated reads from a variety of species, (ii) Illumina reads from 5 isolates for which finished genome sequences were available for comparison, and (iii) Illumina reads from 7 Acinetobacter baumannii isolates for which predicted IS locations were tested using PCR. A total of 20 genomes, including 13 species and 32 distinct IS, were used for validation. ISMapper correctly identified 96% of known IS insertions in the analysis of simulated reads, and 98% in real Illumina reads. Subsampling of real Illumina reads to lower depths indicated ISMapper was reliable for average genome-wide read depths >20x. All ISAba1 insertions identified by ISMapper in the A. baumannii genomes were confirmed by PCR. In each A. baumannii genome, ISMapper successfully identified an IS insertion upstream of the ampC beta-lactamase that could explain phenotypic resistance to third-generation cephalosporins. The utility of ISMapper was further demonstrated by profiling genome-wide IS6110 insertions in 138 publicly available Mycobacterium tuberculosis genomes, revealing lineage-speific inserction and multi inserction hotspot.Conclusions ISMapper provides a rapid and robust method for identifying IS insertion sites direct from short read data, with a high degree of accuracy demonstrated across a wide range of bacteria.