Fig. 9

Alignment of allelic multimodal data during time course of ESC differentiation. A Embedding of allelic sci-RNA-seq and sci-ATAC-seq topic matrices (see Additional file 1: Fig. S8A, B, D, E) learned by MMD-MA, projected in 2D via PCA. In the left-hand panel, each data point represents a cell colored by assay type. In the right-hand panel, each data point represents a cell colored by time point and the mean curve (AUC) score is shown (Additional file 1: Table S5; see Methods). B Embedding of allelic sci-RNA-seq and sci-Hi-C topic matrices (see Additional file 1: Fig. S8A, C, D, F) learned by MMD-MA. Projection and panels as in A. C Embedding of allelic sci-ATAC-seq and sci-Hi-C topic matrices (see Additional file 1: Fig. S8B, C, E, F) learned by MMD-MA. Projection and panels as in A. D As in A, but only using chrX data. E As in B, but only using chrX data. F As in C, but only using chrX data. G Schematic representation of the onset of structural changes throughout the genome and the X chromosome during female ESC differentiation. The proportions of cells with a specific feature are shown for each time point (labeled at top) by shades of blue corresponding to % of cells with that feature (Fig. 4D, E; Fig. 8E). Specific features are listed at left from top to bottom. Three types of genome-wide nuclear configuration detected by sci-Hi-C are schematized to reflect fewer long-range contacts in ESCs, partially condensed chromatin in the intermediate stage, and condensed chromatin in differentiated cells. The X chromosomes (ovals) appear to change structure at the same time as the rest of the genome, and their structure remains similar to that of other chromosomes in ESCs and at the intermediate stage. At the differentiated stage the Xi condenses along with the rest of the genome, but very long-range contacts are further enhanced to form the highly condensed Xi bipartite structure (red). Loss of chromatin accessibility and silencing of genes on the Xi proceed ahead of the structural changes