ITD assembler: an algorithm for internal tandem duplication discovery from short-read sequencing data.

TitleITD assembler: an algorithm for internal tandem duplication discovery from short-read sequencing data.
Publication TypeJournal Article
Year of Publication2016
AuthorsRustagi, N, Hampton, OA, Li, J, Xi, L, Gibbs, RA, Plon, SE, Kimmel, M, Wheeler, DA
JournalBMC Bioinformatics
Date Published2016 Apr 27
KeywordsAlgorithms, Exome, Exons, fms-Like Tyrosine Kinase 3, Humans, Leukemia, Myeloid, Acute, Molecular Diagnostic Techniques, Mutation, Tandem Repeat Sequences

BACKGROUND: Detection of tandem duplication within coding exons, referred to as internal tandem duplication (ITD), remains challenging due to inefficiencies in alignment of ITD-containing reads to the reference genome. There is a critical need to develop efficient methods to recover these important mutational events.

RESULTS: In this paper we introduce ITD Assembler, a novel approach that rapidly evaluates all unmapped and partially mapped reads from whole exome NGS data using a De Bruijn graphs approach to select reads that harbor cycles of appropriate length, followed by assembly using overlap-layout-consensus. We tested ITD Assembler on The Cancer Genome Atlas AML dataset as a truth set. ITD Assembler identified the highest percentage of reported FLT3-ITDs when compared to other ITD detection algorithms, and discovered additional ITDs in FLT3, KIT, CEBPA, WT1 and other genes. Evidence of polymorphic ITDs in 54 genes were also found. Novel ITDs were validated by analyzing the corresponding RNA sequencing data.

CONCLUSIONS: ITD Assembler is a very sensitive tool which can detect partial, large and complex tandem duplications. This study highlights the need to more effectively look for ITD's in other cancers and Mendelian diseases.

Alternate JournalBMC Bioinformatics
PubMed ID27121965
PubMed Central IDPMC4847212
Grant ListU54 HG003273 / HG / NHGRI NIH HHS / United States