A wavelet-based method to exploit epigenomic language in the regulatory region

Bioinformatics. 2014 Apr 1;30(7):908-14. doi: 10.1093/bioinformatics/btt467. Epub 2013 Oct 4.

Abstract

Motivation: Epigenetic landscapes in the regulatory regions reflect binding condition of transcription factors and their co-factors. Identifying epigenetic condition and its variation is important in understanding condition-specific gene regulation. Computational approaches to explore complex multi-dimensional landscapes are needed.

Results: To study epigenomic condition for gene regulation, we developed a method, AWNFR, to classify epigenomic landscapes based on the detected epigenomic landscapes. Assuming mixture of Gaussians for a nucleosome, the proposed method captures the shape of histone modification and identifies potential regulatory regions in the wavelet domain. For accuracy estimation as well as enhanced computational speed, we developed a novel algorithm based on down-sampling operation and footprint in wavelet. We showed the algorithmic advantages of AWNFR using the simulated data. AWNFR identified regulatory regions more effectively and accurately than the previous approaches with the epigenome data in mouse embryonic stem cells and human lung fibroblast cells (IMR90). Based on the detected epigenomic landscapes, AWNFR classified epigenomic status and studied epigenomic codes. We studied co-occurring histone marks and showed that AWNFR captures the epigenomic variation across time.

Availability and implementation: The source code and supplemental document of AWNFR are available at http://wonk.med.upenn.edu/AWNFR.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Animals
  • Cell Line
  • Cluster Analysis
  • Embryonic Stem Cells / metabolism
  • Epigenomics / methods*
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Lung / metabolism
  • Mice
  • Software Design

Substances

  • Histones