Service Incident: New DOI registrations are working again. Re-registration of failed DOI registrations (~500) are still affected by the service incident at DataCite (our DOI registration agency).
Published May 30, 2017 | Version v1
Software Open

Integration of genetic and epigenetic alterations with tissue-specific network reveals regulatory drivers of prostate cancer

  • 1. Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.

Description

We report a novel computational method, RegNetDriver, to identify regulatory drivers of tumorigenesis using combined effects of coding and non-coding single nucleotide variants, structural variants (SVs) and DNA methylation changes in the DNase I hypersensitivity based regulatory network. Integration of whole-genome sequencing, RNA-Seq and methylation data from 521 prostate tumor samples revealed a stronger regulatory impact of SVs, as they effect more transcription factor (TF) hubs in the tissue-specific network. Moreover, a crosstalk between TF hub expression modulated by SVs and methylation levels likely leads to differential expression of target genes. Using RegNetDriver, we report known TFs (ERG and P53) and nominate novel TFs supported by functional validation (ERF, CREB3L1 and POU2F2) as prostate regulatory drivers.

Files

FSig-SNV.zip

Files (334.7 MB)

Name Size Download all
md5:1c28e68165ebb06b80e27dadfce910d5
32.0 kB Preview Download
md5:0b694b45532ca2ae0d9586951da3f410
12.2 MB Download
md5:fe005fa36b60b2735ddecfec4dce495e
5.3 kB Preview Download
md5:fa124e154e548ca7f1a1a2feee3e1623
322.5 MB Download