Figure 3. Application of CellRegMap to iPSCs differentiating towards definitive endoderm.

• A
  Comparison of the CellRegMap GxC interaction test, either considering the first MOFA factor to define the cell context covariance (MOFA 1, x‐axis) or using the leading 10 cellular factors (MOFA 1:10, y‐axis). Shown is a scatter plot of negative log P‐values obtained from the respective tests applied to 4,470 eQTL variants and genes. Horizontal and vertical lines denote the FDR < 5% significance threshold (Benjamin‐Hochberg adjusted). Shown in each quadrant is the number of eQTL with evidence for a GxC effect (e.g., 239 GxC effects are exclusively detected by the model that uses 10 MOFA factors; FDR < 5%).
• B–D
  Representative examples of eQTL with GxC interaction. (B) Left: scatter plot of the first two MOFA factors (capturing cell differentiation as context) with color denoting the time point of collection (days 0, 1, 2 and 3 of endoderm differentiation); middle: identical scatter plot with color encoding the estimated allelic effect for the eQTL variant rs113520162 for the gene IER3; right: allelic effect for the eQTL at rs11180470 for the gene GLIPR1L1. Shown are total allelic effects (${\beta }_G+{\beta }_{\mathit{GxC}}$) for individual cells. The allelic effect size color bar is centered on the persistent genetic effect (${\beta }_G$). Panels on the top and right display marginal densities of cells that have either increased (high, red) or decreased (low, cyan) allelic effects (corresponding to the bottom and top 10% quantiles, respectively). Whereas the GxC effect for the eQTL for IER3 is primarily explained by the first MOFA component, the GxC effect for GLIPR1L1 is captured by the combination of the first two MOFA factors. (C) Analogous presentation as in (B), displaying a scatter plot between MOFA factors 3 and 6 with cells colored by alternative annotations. Left: inferred cell cycle phase (Materials and Methods); Right: allelic effects for an eQTL at rs506770 for HSPA1A (yellow). (D) As in (B, C) scatter plot of MOFA factors 4 and 1. Left: cells colored by cellular respiration (Materials and Methods); Right: allelic effects for the eQTL at rs11763367 for WBSCR27 (green).