➔ Poster
AuthorsMarius Van Den Beek 1, Nick Riddiford, Katarzyna Siudeja, Allison Bardin
1 :
Institut Curie, Institut Curie26 rue dÚlm 75248 PARIS CEDEX 05 - France
Abstract
Transposable Elements (TEs) are mobile genetic elements present in most eukaryotic genomes. By mobilizing to new genomic locations (transposition), transposable elements can alter gene regulatory networks by mutating genes or gene-regulatory elements. Alternatively transposition can alter expression of genes through local epigenetic changes at sites of new transposition events. Transposition therefore plays an important role in evolution and disease, though the frequencies and effects of somatic transposition is not well understood. Detecting and quantifying somatic transposition from current generation short read sequencing technologies is challenging, since most somatic transposition events are rare and will be sparsely sampled when sequencing tissues, which are composed of a pool of cells with heterogenous transposition events.
Here we describe a Galaxy Workflow that can detect germline and somatic transposition events and intersect discovered transposition events with other structural variants. The workflow accurately quantifies the evidence for and against a transposition event from multiple samples and helps researchers evaluate the extent of somatic transposition that can be detected. We have applied this workflow to 19 tumor-normal pairs of
Drosophila Melanogaster, where males frequently lose an X-linked tumor suppressor gene (Siudeja et al., Cell Stem Cell, 2015). This leads to the formation of a clonally expanded cell-mass. Using our workflow we can (1) detect an overall increase of somatic transposition as compared to a control tissues, (2) detect new transposable element insertions at the breakpoints of deletion at the tumor suppressor gene.
This demonstrates theimportance of whole-genome sequencing approaches for detecting mutations in diseases.
