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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-01, Vol.114 (5), p.E733-E740
Main Authors: Tang, Zuojian, Steranka, Jared P., Ma, Sisi, Grivainis, Mark, Rodić, Nemanja, Huang, Cheng Ran Lisa, Shih, Ie-Ming, Wang, Tian-Li, Boeke, Jef D., Fenyö, David, Burns, Kathleen H.
Format: Article
Language:English
Subjects:
Biological Sciences
Genomes
Mammals
Mutation
Ovarian cancer
PNAS Plus
Reliability
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1619797114