Whole genome sequencing (WGS) has enabled the discovery of genomic structural variants (SVs), including those targeting intergenic and intronic non-coding regions that eluded previous exome focused strategies. However, the field currently lacks an automated tool that analyzes SV candidates to identify recurrent SVs and their targeted sites (hotspot regions), visualizes these genomic events within the context of various functional elements, and evaluates their potential effect on gene expression. To address this, we developed SV-HotSpot, an automated tool that integrates SV candidates, copy number alterations, gene expression, and genome annotations (e.g. gene and regulatory elements) to discover, annotate, and visualize recurrent SVs and their targeted hotspot regions that may affect gene expression. We applied SV-HotSpot to WGS and matched transcriptome data from metastatic castration resistant prostate cancer patients and rediscovered recurrent SVs targeting coding and non-coding functional elements known to promote prostate cancer progression and metastasis. SV-HotSpot provides a valuable resource to integrate SVs, gene expression, and genome annotations for discovering biologically relevant SVs altering coding and non-coding genome. SV-HotSpot is available at https://github.com/ChrisMaherLab/SV-HotSpot.
Bibliographical noteFunding Information:
This work has been supported by a Prostate Cancer Foundation Challenge Award (to C.A.M., F.Y.F., and S.M.D.), a Prostate Cancer Foundation Young Investigator Award (to D.A.Q., R.Y., and S.G.Z.) and a BRCA Foundation Young Investigator Award (to D.A.Q.), an American Cancer Society Institutional Research Grant Number IRG-18-158-61 (to H.X.D.), and an NIH National Cancer Institute Grant Number R01CA174777 (to S.M.D.).
© 2020, The Author(s).
- DNA Copy Number Variations
- Genome, Human
- Genomic Structural Variation
- Prostatic Neoplasms, Castration-Resistant/genetics
- Whole Genome Sequencing
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural