Extended Data Fig. 3: Meningioma DNA methylation grouping using SeSAMe to control for the influence of CNVs on β values compared to approaches that do not control for the influence of CNVs on β values.
From: Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities
a, Unsupervised hierarchical clustering of meningiomas from the discovery cohort (n = 200) using 2,000 differentially methylated DNA probes from the minfi preprocessing pipeline, which does not control for the influence of CNVs on β values. SeSAME meningioma DNA methylation groups (21% altered by minfi) are shown beneath the vertical dendrogram. b, K-means consensus clustering of meningiomas from the discovery and validation cohorts (n = 565) using differentially methylated DNA probes and β values from SeSAMe or minfi. SeSAMe consensus clustering identifies 3 groups as the optimal number, but minfi consensus clustering is unable to discriminate between 3 and 4 clusters. c, Continuous distribution functions (CDFs) from K-means consensus clustering of meningiomas from the discovery and validation cohorts (n = 565) using differentially methylated DNA probes and β values from SeSAMe or minfi. SeSAMe CDFs validated 3 groups as the optimal number, which was quantitatively different from 3 minfi groups (p = 1.341 × 10−4) or 4 minfi groups (p < 2.2 × 10−6) (Kolmogorov-Smirnov test). d, Kaplan–Meier curves for meningioma local freedom from recurrence (n = 565) across minfi DNA methylation groups fails to identify a grouping scheme with non-redundant differences in clinical outcomes, in contrast to SeSAMe DNA methylation groups (Fig. 1c) (Log-rank tests). minfi meningioma DNA methylation grouping schemed comprised of 3, 4, 5, or 6 groups are designated by letters A-C, A-D, A-E, or A-F, respectively.
