Gu, HongcangBock, ChristophMikkelsen, Tarjei SJäger, NatalieSmith, ZacharyTomazou, EleniGnirke, AndreasLander, EricMeissner, Alexander2015-01-122010Gu, Hongcang, Christoph Bock, Tarjei S. Mikkelsen, Natalie Jäger, Zachary D. Smith, Eleni Tomazou, Andreas Gnirke, Eric Steven Lander, and Alexander Meissner. 2010. “Genome-Scale DNA Methylation Mapping of Clinical Samples at Single-Nucleotide Resolution.” Nature Methods 7 (2): 133–136.1548-70911548-7105http://nrs.harvard.edu/urn-3:HUL.InstRepos:13606766Bisulfite 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.en-USJournal Article2015-01-1210.1038/nmeth.1414