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Cited by 347

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

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

Open access
Wu, Hao, Xu, Tianlei, Feng, Hao, Chen, Li, Li, Ben, Yao, Bing, Qin, Zhaohui, Jin, Peng, Conneely, Karen N.·2015·Nucleic Acids Research

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.

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Metadata

Authors
Wu, H., Xu, T., Feng, H., Chen, L., Li, B., Yao, B., Qin, Z., Jin, P., & Conneely, K. N.
Venue
Nucleic Acids Research
Published
2015-07-15
Volume
43
Issue
21
Pages
gkv715
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W1678624296
Cited by
347
References
8
FWCI
6.95
Type
journal article
Language
en
Open access
gold

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