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This article is part of the supplement: Proceedings of the Third Annual RECOMB Satellite Workshop on Massively Parallel Sequencing (RECOMB-seq 2013)

Open Access Proceedings

Bellerophon: a hybrid method for detecting interchromo-somal rearrangements at base pair resolution using next-generation sequencing data

Matthew Hayes and Jing Li*

Author Affiliations

Department of Electrical Engineering and Computer Science, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, USA

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BMC Bioinformatics 2013, 14(Suppl 5):S6  doi:10.1186/1471-2105-14-S5-S6

Published: 10 April 2013

Abstract

Background

Somatically-acquired translocations may serve as important markers for assessing the cause and nature of diseases like cancer. Algorithms to locate translocations may use next-generation sequencing (NGS) platform data. However, paired-end strategies do not accurately predict precise translocation breakpoints, and "split-read" methods may lose sensitivity if a translocation boundary is not captured by many sequenced reads. To address these challenges, we have developed "Bellerophon", a method that uses discordant read pairs to identify potential translocations, and subsequently uses "soft-clipped" reads to predict the location of the precise breakpoints. Furthermore, for each chimeric breakpoint, our method attempts to classify it as a participant in an unbalanced translocation, balanced translocation, or interchromosomal insertion.

Results

We compared Bellerophon to four previously published algorithms for detecting structural variation (SV). Using two simulated datasets and two prostate cancer datasets, Bellerophon had overall better performance than the other methods. Furthermore, our method accurately predicted the presence of the interchromosomal insertions placed in our simulated dataset, which is an ability that the other SV prediction programs lack.

Conclusions

The combined use of paired reads and soft-clipped reads allows Bellerophon to detect interchromosomal breakpoints with high sensitivity, while also mitigating losses in specificity. This trend is seen across all datasets examined. Because it does not perform assembly on soft-clipped subreads, Bellerophon may be limited in experiments where sequence read lengths are short.

Availability

The program can be downloaded from http://cbc.case.edu/Bellerophon webcite