Figure 4. Association of aberrant methylation with clone-specific effects (see also Tables S1A, S1B, and S3A, and Figure S4).
A) Heat map showing hierarchical clustering of 9,310 aberrant CpGs, cells are colored according to whether they are not aberrant (None), iPSC loss, somatic memory, or iPSC gain in each of the 49 samples. B) Heatmap showing odds ratios (ORs) from Fisher’s exact test of overlap between CpGs in aberrant CpG classes (columns) and those in CpG predictor classes. For CpG predictor classes, the reference is sites not associated with any category (the “None” category). For aberrant CpG classes, the reference is sites showing no aberrant methylation in any sample (the “Not Aberrant” category). Cells are colored according to −logP-value with positive values indicating over-enrichment and negative indicating under-enrichment. Cells with non-significant results (FDR > 0.05) do not have an OR reported. C) Heatmap showing ORs for the overlap between gene-level aberrant CpG classes and gene-level CpG predictor classes. Cells are colored according to −logP-value. D) OR’s for the overlap of genes enriched for aberrant classification (columns) and genes where the expression values from RNA-seq were associated with each predictor classification (rows). Cells are colored according to −logP-value. (E) Venn diagram showing the intersection of genes in aberrant regions in Lister et al. and genes aberrantly methylated in this study. F) List of 60 genes that show overlap in aberrant methylation between Lister et al. and this study. Genes are annotated by whether they showed gene-level aberrant methylation for iPSC gain, somatic memory, iPSC loss, or gene-level clone-specific enrichment. MYC-like CpG indicates the gene carried one or more iPSC gain CpGs associated with a MYC or MYC-like binding site. Cells are black if the variable is present (overlaps a Lister et al region; shows gene-level enrichment for iPSC gain, somatic memory, or iPSC loss; shows gene-level enrichment for the clone-specific CpG predictor class, or carries at least one CpG with a predicted Myc bindings site), and grey if absent.