ERRBS is a slightly modified version of RRBS 36,37 . Libraries were prepared by MspI restriction enzyme digestion of high molecular weight genomic DNA , followed by end repair , size selection , bisulfite conversion and library amplification as previously described 38,39 . Libraries were sequenced on a HiSeq 2000 Illumina machine using 75 bp single - end reads . Data alignment was performed to human genome hg19 as previously described ( see data analysis description ) 38,39 . Average reads per sample were 138,596,488 with a mean alignment rate of unique reads of 63.7 % , covering on average 4,399,235 CpGs per sample at a minimum threshold coverage of 10X. Average coverage depth per CpG was 72.3 and average bisulfite conversion was 99.86 % determined as previously described 38,39 . See Supplementary Table 3 for detailed sequencing statistics . A subset of patient samples were processed using SeqCap Epi 4 M CpGiant Enrichment kit ( NimbleGen - Roche ) and SureSelect XT Human Methyl - Seq ( Agilent Technologies ) per manufacturer 's recommendations . These were sequenced using a paired - end 100bp approach on a HiSeq 2000 ( Illumina , Inc. ) .