Human transposon insertion profiling: Analysis, visualization and identification of somatic LINE-1 insertions in ovarian cancer

Zuojian Tang, Jared P. Steranka, Sisi Ma, Mark Grivainis, Nemanja Rodić, Cheng Ran Lisa Huang, Ie Ming Shih, Tian Li Wang, Jef D. Boeke, David Fenyö, Kathleen H. Burns

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Mammalian genomes are replete with interspersed repeats reflecting the activity of transposable elements. These mobile DNAs are self-propagating, and their continued transposition is a source of both heritable structural variation as well as somatic mutation in human genomes. Tailored approaches to map these sequences are useful to identify insertion alleles. Here, we describe in detail a strategy to amplify and sequence long interspersed element-1 (LINE-1, L1) retrotransposon insertions selectively in the human genome, transposon insertion profiling by next-generation sequencing (TIPseq). We also report the development of a machine-learning-based computational pipeline, TIPseqHunter, to identify insertion sites with high precision and reliability. We demonstrate the utility of this approach to detect somatic retrotransposition events in highgrade ovarian serous carcinoma.

Original languageEnglish (US)
Pages (from-to)E733-E740
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number5
DOIs
StatePublished - Jan 31 2017

Bibliographical note

Funding Information:
This work was supported by the Sol Goldman Pancreatic Cancer Research Center and the Health, Empowerment, Research, and Awareness Women's Cancer Foundation (N.R.); a Burroughs Wellcome Fund Career Award for Biomedical Scientists Program (K.H.B.); US NIH Awards R01CA161210 (to J.D.B.), R01CA163705 (to K.H.B.), and R01GM103999 (to K.H.B.); as well as National Institute of General Medical Sciences Center for Systems Biology of Retrotransposition Grant P50GM107632 (to K.H.B. and J.D.B.).

Keywords

  • Human
  • LINE-1
  • Ovarian cancer
  • Retrotransposon
  • TIPseq

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