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Open Access Methodology article

ChopSticks: High-resolution analysis of homozygous deletions by exploiting concordant read pairs

Tomohiro Yasuda1*, Shin Suzuki1, Masao Nagasaki2 and Satoru Miyano1

Author affiliations

1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

2 Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573, Japan

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Citation and License

BMC Bioinformatics 2012, 13:279  doi:10.1186/1471-2105-13-279

Published: 30 October 2012

Abstract

Background

Structural variations (SVs) in genomes are commonly observed even in healthy individuals and play key roles in biological functions. To understand their functional impact or to infer molecular mechanisms of SVs, they have to be characterized with the maximum resolution. However, high-resolution analysis is a difficult task because it requires investigation of the complex structures involved in an enormous number of alignments of next-generation sequencing (NGS) reads and genome sequences that contain errors.

Results

We propose a new method called ChopSticks that improves the resolution of SV detection for homozygous deletions even when the depth of coverage is low. Conventional methods based on read pairs use only discordant pairs to localize the positions of deletions, where a discordant pair is a read pair whose alignment has an aberrant strand or distance. In contrast, our method exploits concordant reads as well. We theoretically proved that when the depth of coverage approaches zero or infinity, the expected resolution of our method is asymptotically equal to that of methods based only on discordant pairs under double coverage. To confirm the effectiveness of ChopSticks, we conducted computational experiments against both simulated NGS reads and real NGS sequences. The resolution of deletion calls by other methods was significantly improved, thus demonstrating the usefulness of ChopSticks.

Conclusions

ChopSticks can generate high-resolution deletion calls of homozygous deletions using information independent of other methods, and it is therefore useful to examine the functional impact of SVs or to infer SV generation mechanisms.