Fig. 2. Multi-omics Factor Analysis reveals coordinated epigenetic and transcriptomic variation at enhancer elements during germ layer commitment.

a, Percentage of variance explained (R²) by each MOFA factor (rows) across data modalities (columns). b, Scatter plot of MOFA Factor 1 (x-axis) and MOFA Factor 2 (y-axis). Cells are coloured according to their lineage assignment (n=840). c, Scatter plots showing differential DNA methylation (%, x-axis) and chromatin accessibility (%, y-axis) at lineage-specific enhancers at E7.5. Comparisons are ectoderm vs non-ectoderm cells (left), endoderm vs non-endoderm cells (middle) and mesoderm vs non-mesoderm cells (right). Black dots depict gene-enhancer pairs with significant changes in RNA expression and methylation or accessibility (Pearson’s chi-squared test, FDR<10%). d, Transcription Factor (TF) motif enrichment at lineage-defining enhancers. Shown is motif enrichment (Fisher’s exact test, -log10 q-value, y-axis) versus differential RNA expression (log fold change, x-axis) of the corresponding TF. The analysis is performed separately for ectoderm- (left), endoderm- (middle) and mesoderm- (right) defining enhancers. TFs with significant motif enrichment (FDR<1%) and differential RNA expression (edgeR quasi-likelihood test, FDR<1%) are labelled.