Statistical methods for detecting differentially methylated regions based on MethylCap-seq data

Deepak Nag Ayyala, David E. Frankhouser, Javkhlan Ochir Ganbat, Guido Marcucci, Ralf Bundschuh, Pearlly Yan, Shili Lin

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

DNA methylation is a well-established epigenetic mark, whose pattern throughout the genome, especially in the promoter or CpG islands, may be modified in a cell at a disease stage. Recently developed probabilistic approaches allow distributing methylation signals at nucleotide resolution from MethylCap-seq data. Standard statistical methods for detecting differential methylation suffer from 'curse of dimensionality' and sparsity in signals, resulting in high false-positive rates. Strong correlation of signals between CG sites also yields spurious results. In this article, we review applicability of highdimensional mean vector tests for detection of differentially methylated regions (DMRs) and compare and contrast such tests with other methods for detecting DMRs. Comprehensive simulation studies are conducted to highlight the performance of these tests under different settings. Based on our observation, we make recommendations on the optimal test to use. We illustrate the superiority of mean vector tests in detecting cancer-related canonical gene pathways, which are significantly enriched for acute myeloid leukemia and ovarian cancer.

Original languageEnglish (US)
Pages (from-to)926-937
Number of pages12
JournalBriefings in Bioinformatics
Volume17
Issue number6
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • Differentially methylated regions
  • High dimensionality
  • Mean vector test
  • MethylCap-seq

ASJC Scopus subject areas

  • Information Systems
  • Molecular Biology

Fingerprint Dive into the research topics of 'Statistical methods for detecting differentially methylated regions based on MethylCap-seq data'. Together they form a unique fingerprint.

  • Cite this

    Ayyala, D. N., Frankhouser, D. E., Ganbat, J. O., Marcucci, G., Bundschuh, R., Yan, P., & Lin, S. (2016). Statistical methods for detecting differentially methylated regions based on MethylCap-seq data. Briefings in Bioinformatics, 17(6), 926-937. https://doi.org/10.1093/BIB/BBV089