INDELseek: detection of complex insertions and deletions from next-generation sequencing data

BMC Genomics

Software

Anskar Y. H. Leung¹  Ava Kwong²  Edmond S. K. Ma³  Tsun Leung Chan³  Chun Hang Au³ 

[1] Department of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR;Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR;Department of Surgery and Cancer Genetics Center, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong SAR;Hong Kong Hereditary Breast Cancer Family Registry, Shau Kei Wan, Hong Kong SAR;Division of Molecular Pathology, Department of Pathology, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong SAR;

关键词: Complex indel;    Variant calling;    Bioinformatics;    Next-generation sequencing;   

DOI  :  10.1186/s12864-016-3449-9

 received in 2016-08-05, accepted in 2016-12-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundComplex insertions and deletions (indels) from next-generation sequencing (NGS) data were prone to escape detection by currently available variant callers as shown by large-scale human genomics studies. Somatic and germline complex indels in key disease driver genes could be missed in NGS-based genomics studies.ResultsINDELseek is an open-source complex indel caller designed for NGS data of random fragments and PCR amplicons. The key differentiating factor of INDELseek is that each NGS read alignment was examined as a whole instead of “pileup” of each reference position across multiple alignments. In benchmarking against the reference material NA12878 genome (n = 160 derived from high-confidence variant calls), GATK, SAMtools and INDELseek showed complex indel detection sensitivities of 0%, 0% and 100%, respectively. INDELseek also detected all known germline (BRCA1 and BRCA2) and somatic (CALR and JAK2) complex indels in human clinical samples (n = 8). Further experiments validated all 10 detected KIT complex indels in a discovery cohort of clinical samples. In silico semi-simulation showed sensitivities of 93.7–96.2% based on 8671 unique complex indels in >5000 genes from dbSNP and COSMIC. We also demonstrated the importance of complex indel detection in accurately annotating BRCA1, BRCA2 and TP53 mutations with gained or rescued protein-truncating effects.ConclusionsINDELseek is an accurate and versatile tool for complex indel detection in NGS data. It complements other variant callers in NGS-based genomics studies targeting a wide spectrum of genetic variations.

【 授权许可】

CC BY   
© The Author(s). 2017