SeSAMe associates mouse strain-specific methylations to phenotypes. (A) t-SNE embedding of methylomes of tissue samples from 25 different strains. SNP-influenced probes are masked. (B) An UpSet plot of strain-specific differential methylated CpGs (SDMCs) showing strong dependence on tissue types. (C) Enrichment of SDMCs shared across tissues in CTCF binding sites (red), consistent intermediate methylation (IM, green) and variably methylated regions (VMR, blue). (D) Enrichment of tissue-specific SDMCs in enhancer regions among different chromatin states (from ENCODE ChromHMM). SDMCs from all strains are merged to perform enrichment test. (E) Example differentially methylated regions at the Nap1l5/Herc3 locus, specific to the BTBR strain. (F) The number of frontal lobe brain SDMCs in different strains. Only strains with both sexes represented are shown. Frontal lobe brain SDMCs with LP/J showed the most methylation loss. (G) Transcription factor binding site (TFBS) enrichment of LP/J-specific hypomethylation. nQ, nD and nO represent the size of query, database and overlap CpGs set. (H) The number of liver SDMCs in different strains. Liver SDMCs with wild-derived strains showed more hyper- than hypomethylation. (I) Enrichment of liver-specific SDMCs at Polycomb repressive complex targets and hepatocyte-associated transcription factors.