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Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E733-E740. doi: 10.1073/pnas.1619797114. Epub 2017 Jan 17.

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

Author information

1
Center for Health Informatics and Bioinformatics, NYU Langone Medical Center, New York, NY 10016.
2
Institute for Systems Genetics, NYU Langone Medical Center, New York, NY 10016.
3
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
4
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
5
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
6
Institute for Systems Genetics, NYU Langone Medical Center, New York, NY 10016; jef.boeke@nyumc.org david@fenyolab.org kburns@jhmi.edu.
7
Center for Health Informatics and Bioinformatics, NYU Langone Medical Center, New York, NY 10016; jef.boeke@nyumc.org david@fenyolab.org kburns@jhmi.edu.
8
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; jef.boeke@nyumc.org david@fenyolab.org kburns@jhmi.edu.

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 high-grade ovarian serous carcinoma.

KEYWORDS:

LINE-1; TIPseq; human; ovarian cancer; retrotransposon

PMID:
28096347
PMCID:
PMC5293032
DOI:
10.1073/pnas.1619797114
[Indexed for MEDLINE]
Free PMC Article

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