Fig. 4: Allele-specific expression reveals interactions with fundamental cellular processes.

a Illustration of eQTL affected by cellular context. Left: Schematic of cellular contexts affecting a regulatory element containing an eQTL SNP, and thus affecting allele-specific expression. Right: Allele-specific expression variation for two exemplar eQTL SNPs that tag cancer GWAS variants and display GxE interactions (FDR < 10%). The eQTL for RNASET2 (rs2247315) tags a risk variant for basal cell carcinoma, and is responsive to cellular respiration, while that for SNRPC (rs9380455) tags a risk variant for prostate cancer and is responsive to the cell cycle G2/M transition (Table S13). Cellular contexts for each cell were inferred by GO annotations of coexpression modules (Methods). Shaded regions indicate standard error (+/− 1 SEM; Methods). b Results summary: numbers of eQTL (from Fig. 2; Methods) identified as displaying GxE interactions with pseudotime (purple), displaying GxE interactions with other cellular contexts but not with pseudotime, (after appropriately accounting for pseudotime, red), displaying GxE interactions with both pseudotime and at least one other cellular context (yellow), and displaying no GxE interactions at all (grey). Significance is assessed at FDR < 10%. c Higher order interaction example: an eQTL variant for EIF5A (rs7503161) is affected by a GxExE higher order interaction with both pseudotime and the G1/S transition. Left panel: Effects of respiration state on ASE for cells with low and high pseudotime. Lines shown are linear regressions with 95% confidence intervals for the 30% of cells with lowest and highest values for pseudotime. Right panel: Heatmap of averaged ASE for cells falling within the specified windows of pseudotime and respiration state. Only values for windows containing n > 30 cells are shown (n = 6423 cells in total).