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

BMC Bioinformatics

Proceedings

Matthew Hayes¹  Jing Li¹ 

[1] Department of Electrical Engineering and Computer Science, Case Western Reserve University, Euclid Ave, 10900, Cleveland, OH, USA;

关键词: Simulated Dataset;    Read Pair;    Balance Translocation;    Human Reference Genome;    Translocation Breakpoint;   

DOI  :  10.1186/1471-2105-14-S5-S6

来源: Springer

【 摘 要 】

BackgroundSomatically-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.ResultsWe 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.ConclusionsThe 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.AvailabilityThe program can be downloaded from http://cbc.case.edu/Bellerophon

【 授权许可】

Unknown   
© Hayes et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.