Coverage recommendations for methylation analysis by whole-genome bisulfite sequencing

Nat Methods. 2015 Mar;12(3):230-2, 1 p following 232. doi: 10.1038/nmeth.3152. Epub 2014 Nov 2.


Whole-genome bisulfite sequencing (WGBS) allows genome-wide DNA methylation profiling, but the associated high sequencing costs continue to limit its widespread application. We used several high-coverage reference data sets to experimentally determine minimal sequencing requirements. We present data-derived recommendations for minimum sequencing depth for WGBS libraries, highlight what is gained with increasing coverage and discuss the trade-off between sequencing depth and number of assayed replicates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / physiology
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / physiology
  • CpG Islands*
  • DNA Methylation*
  • Data Interpretation, Statistical
  • Databases, Genetic
  • Embryonic Stem Cells / physiology
  • Genome, Human
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods*
  • Sulfites


  • Sulfites
  • hydrogen sulfite