Inspection of the concordance of methylation states in the five iPSC lines showed that 69% of the CG-DMRs were aberrant with respect to the ES cells in at least two iPSC lines, with 16% being confirmed in all five iPSC lines (Fig. 3c and Supplementary Table 3). The majority of CG-DMRs (80%) occurred at CG islands, and to a lesser extent near or within genes (62%), with 29% and 19% located within 2 kb of transcriptional start and end sites, respectively (Fig. 3d). Analysis of biological processes attributed to genes proximal to CG-DMRs in each line or common to all iPSC lines did not identify any enrichment of specific processes, indicating that disruption of the normal regulation of these genes could affect many aspects of cellular function. Closer inspection of the CG-DMRs confirmed in all five iPSC lines revealed that the vast majority of them (119 of 130, or 92%) were hypomethylated in the iPSC lines, indicating that the general deficiency in resetting DNA methylation patterns during reprogramming is insufficient methylation. Notably, the remaining 11 CG-DMRs hypermethylated in all iPSC
