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Author Notes:

To whom correspondence should be addressed. Tel: +1 404 727 8633; Fax: +404 727 1370; Email: hao.wu@emory.edu

Conflict of interest statement. None declared.

Subjects:

Research Funding:

Funding for open access charge: Departmental startup fund.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • DEPENDENT DNA METHYLATION
  • SEQ DATA
  • CANCER
  • EXPRESSION
  • METHYLOME
  • SOFTWARE
  • PACKAGE
  • MODEL

Detection of differentially methylated regions from whole-genome bisulfite sequencing data without replicates

Journal Title:

Nucleic Acids Research

Volume:

Volume 43, Number 21

Publisher:

, Pages e141-e141

Type of Work:

Article | Final Publisher PDF

Abstract:

DNA methylation is an important epigenetic modification involved in many biological processes and diseases. Recent developments in whole genome bisulfite sequencing (WGBS) technology have enabled genome-wide measurements of DNA methylation at single base pair resolution. Many experiments have been conducted to compare DNA methylation profiles under different biological contexts, with the goal of identifying differentially methylated regions (DMRs). Due to the high cost of WGBS experiments, many studies are still conducted without biological replicates. Methods and tools available for analyzing such data are very limited.We develop a statistical method, DSS-single, for detecting DMRs from WGBS data without replicates. We characterize the count data using a rigorous model that accounts for the spatial correlation of methylation levels, sequence depth and biological variation. We demonstrate that using information from neighboring CG sites, biological variation can be estimated accurately even without replicates. DMR detection is then carried out via a Wald test procedure. Simulations demonstrate that DSS-single has greater sensitivity and accuracy than existing methods, and an analysis of H1 versus IMR90 cell lines suggests that it also yields the most biologically meaningful results. DSS-single is implemented in the Bioconductor package DSS.

Copyright information:

© The Author(s) 2015.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

Creative Commons License

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