Figure 1

Genome-wide DNA methylation analysis. (a) Schema for the extraction of probes for unsupervised two-way hierarchical cluster analysis. Problematic probes indicate probes with missing values due to inadequate hybridization with an extremely low signal and with the SNPs at minor allele frequency > 0.1. |Δβ|, absolute difference in the average β-value between recurrent miscarriage and artificial abortion. SD, standard deviation. (b) Heat maps of unsupervised two-way hierarchical cluster analysis of 10 samples (recurrent miscarriage (RM); n = 5, artificial abortion (AA); n = 5) using differentially methylated probes in the chorionic villi and the decidua. The cluster analysis was performed for differentially methylated probes on all regions (9073 and 4412 probes), and separately for promoter regions (1289 and 2009 probes) and enhancer regions (2960 and 829 probes) in chorionic villi and decidua, respectively. Colors correspond to β-values as indicated (zero means a site is completely unmethylated while one means it is completely methylated). In the sample column, beige and red indicate recurrent miscarriage and artificial abortion, respectively. (c) Consensus clustering matrix of 9073 differentially methylated probes in chorionic villi for k = 2. Consensus index values range from 0 (higher dissimilar) to 1 (higher similar). (d) Cumulative distribution function plots from the consensus matrices for k = 2 to k = 6.