To understand the relationship among different tissue/cell samples beyond the constraints of a tree representation, we also studied the full similarity matrix of each mark in relevant chromatin states (Fig. S9) and also visualized the principal dimensions of epigenomic variation using multidimensional scaling (MDS) analysis (Fig. S10). The pairwise similarity matrices of different marks were most effective in distinguishing different subsets of the samples, with H3K4me1 in Enh primarily capturing immune cell similarities, and H3K27me3 in ReprPC capturing pluripotent cell similarities (Fig. S9). In the MDS analysis, the first four dimensions of variation for most marks separated several major sample groups (Extended Data 7a-i), with some subtle differences between marks. For example, pluripotent cells and immune cells were two strong outliers in the first two dimensions of H3K4me1 variation in Enh (Fig. 6b), but H3K27me3 in ReprPC showed more uniform spreading of reference epigenomes (Fig. 6c), consistent with the coverage distributions of immune and pluripotent cells for the corresponding chromatin states (Fig. 5b). For most marks, the first five dimensions captured most of the variance, with additional dimensions capturing only 4-6% for each mark (Extended Data 7).
