Fig. 2

Differential methylation within the stomach and between the stomach and adjacent tissues. A Displayed are the top 15 DM genes in all comparisons, ranked by the highest number of DM CpGs normalized to total CpGs/gene. Left: a heatmap of average DNA methylation (beta) values per gene. Color code ranges from 0 (unmethylated, blue) to 1 (methylated, red). Stars refer to (homeodomain) transcription factors (TFs). Right: the percentage of significantly DM CpGs out of the total number of interrogated CpGs per gene; color code ranges from white to dark green refer to percentage. B Table of selected gene ontology (GO) terms enriched in antrum vs. fundus, determined with StringDB [85]. C Average promoter methylation is plotted against the normalized gene expression values. The selected genes showed negative (GATA4, UPK1B, EYA2) and positive (CDX2) correlations between promoter methylation and gene expression. D Schematic representation of expression patterns of several DM TFs in different stomach regions, based on mucosoid and biopsy data sets (Additional files 3, 13: Fig. S3, Table S7). Asterisks indicate genes not differentially expressed in the mucosoid data set. E Enrichment and depletion of DM CpGs according to different genomic features—heatmap comparisons between stomach regions and between the stomach and adjacent tissues. Shown are significantly enriched (log odds ratio > 0.6) and depleted (log odds ratio <  − 0.6) histone modifications and TF binding sites (FDR < 0.05). Color code ranges from blue (depleted) to red (enriched); light gray refers to a log odds ratio between − 0.6 and 0.6; shaded squares display nonsignificant results; Pol2—Polymerase 2 subunit. F Stomach- and stomach cell-type-specific gene sets—percentages of DM genes between stomach regions (green) and between the stomach and adjacent tissues (purple)