Amplicon Indel Hunter Is a Novel Bioinformatics Tool to Detect Large Somatic Insertion/Deletion Mutations in Amplicon-Based Next-Generation Sequencing Data

The Journal of Molecular Diagnostics : JMD
Sabah KadriJeremy P Segal

Abstract

Amplicon-based targeted next-generation sequencing assays are used widely to test for clinically relevant somatic mutations in cancer. However, accurate detection of large insertions and deletions (indels) via these assays remains challenging. Sequencing reads that cover these anomalies are, by definition, different from the reference sequence, and lead to variable performance of alignment algorithms. Reads with large indels may be aligned incorrectly, causing incorrect calls, or may remain unmapped and essentially ignored by downstream informatics pipeline sub-processes. Herein, we describe Amplicon Indel Hunter (AIH), a novel large (>5-bp) indel detection method that is reference genome independent and highly sensitive for the identification of somatic indels in amplicon-based, paired-end, next-generation sequencing data. We validated the algorithm for sensitivity and specificity using a set of clinical cancer samples with Clinical Laboratory Improvement Amendment-confirmed indels as well as in silico mutated data sets. The AIH detected 100% of tested large indels with relatively higher mutant allele frequencies compared with a variety of traditional aligners, which showed variably reduced sensitivity and specificity by compa...Continue Reading

References

Jul 10, 2001·British Journal of Haematology·F M Abu-DuhierJ T Reilly
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Mar 20, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Eric J DuncavageJohn D Pfeifer
Oct 31, 2014·Archives of Pathology & Laboratory Medicine·Birgitte B SimenZi-Xuan Wang

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Citations

May 29, 2016·The Journal of Molecular Diagnostics : JMD·Jeremy P Segal
Jan 17, 2017·Expert Review of Molecular Diagnostics·Jeremy Davis-TurakGary Hardiman
Apr 25, 2019·International Journal of Cancer. Journal International Du Cancer·Angela BelliniGudrun Schleiermacher

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