Fig. 4: Identification of cancer-related disruption events by applying MR/MN to MethSig.
From: DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution
a, Schematic of the development of the MR/MN metric. (1) The DMP status is assigned for each CpG in the gene promoter across the cohort. (2) Each DMP is characterized as regulatory or nonregulatory based on whether hypermethylation of the CpG reduces gene expression of the cognate gene across the cohort. (3) MR and MN values for each gene are calculated based on the aggregated DNA methylation status of regulatory and nonregulatory CpGs in each gene promoter across the entire cohort. b, log–log scatter plot displaying the common calculable MR/MN ratios for each gene in LUAD (y axis) and LUSC (x axis). On the density plot, subtype-specific calculable MR/MN ratios according to genes are indicated. The formula for determining the MR/MN ratio for each gene is illustrated in the lower left corner. The colors in the log–log scatter plot represent the direction of deviation of MR/MN from 1 for each subtype and its significance. c, Functional enrichment analysis with Gene Ontology (GO) terms for MethSig genes with MR/MN > 1 (top) and MR/MN < 1 (bottom). d, Kaplan–Meier curves based on the expression of the MethSig cancer genes with an MR/MN > 1 (CYP4F2, MSC and EIF5A2) associated with worse DFS in the TRACERx cohort (multivariate Cox analysis). e, Odds ratio (OR) highlighting the co-occurrence of promoter DNA hypermethylation events for MR/MN > 1 MethSig cancer genes and driver mutations in canonical TSGs in LUAD. Significant co-occurrences are labeled.
