Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution

Nat Methods. 2010 Feb;7(2):133-6. doi: 10.1038/nmeth.1414. Epub 2010 Jan 10.


Bisulfite sequencing measures absolute levels of DNA methylation at single-nucleotide resolution, providing a robust platform for molecular diagnostics. We optimized bisulfite sequencing for genome-scale analysis of clinical samples: here we outline how restriction digestion targets bisulfite sequencing to hotspots of epigenetic regulation and describe a statistical method for assessing significance of altered DNA methylation patterns. Thirty nanograms of DNA was sufficient for genome-scale analysis and our protocol worked well on formalin-fixed, paraffin-embedded samples.

Publication types

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

MeSH terms

  • Base Sequence
  • Chromosome Mapping / methods*
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / genetics*
  • DNA Methylation / genetics*
  • DNA, Neoplasm / genetics*
  • Genetic Testing / methods*
  • Humans
  • Molecular Sequence Data
  • Nucleotides / genetics
  • Reproducibility of Results
  • Sensitivity and Specificity


  • DNA, Neoplasm
  • Nucleotides