Introduction

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.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.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.

Publications

  1. ITD assembler: an algorithm for internal tandem duplication discovery from short-read sequencing data.
    Cite this
    Rustagi N, Hampton OA, Li J, Xi L, Gibbs RA, Plon SE, Kimmel M, Wheeler DA, 2016-04-01 - BMC bioinformatics

Credits

  1. Navin Rustagi
    Developer

    Department of Statistics, Rice University

  2. Oliver A Hampton
    Developer

    Department of Molecular and Human Genetics, Baylor College of Medicine, United States of America

  3. Jie Li
    Developer

    Department of Dermatology, Xiangya Hospital, China

  4. Liu Xi
    Developer

    Human Genome Sequencing Center, Baylor College of Medicine, United States of America

  5. Richard A Gibbs
    Developer

    Department of Molecular and Human Genetics, Baylor College of Medicine, United States of America

  6. Sharon E Plon
    Developer

    Department of Pediatrics/Hematology-Oncology, Texas Children's Hospital, United States of America

  7. Marek Kimmel
    Developer

    Human Genome Sequencing Center, Baylor College of Medicine, United States of America

  8. David A Wheeler
    Investigator

    Department of Molecular and Human Genetics, Baylor College of Medicine, United States of America

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Summary
AccessionBT000519
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesC
User InterfaceTerminal Command Line
Download Count0
Country/RegionUnited States of America
Submitted ByDavid A Wheeler