Fig. 4

Inference of gene expression for drug-treated A549 lung cancer cells using chromatin accessibility. A Cell-wise Pearson correlation (y-axis) of inferred and measured gene expression by different methods (x-axis): CMOT (p = 25%, 50%, 75%, 100%), Seurat, MOFA+ (Additional File 1: Tables S17-S20). See Additional File 1: Fig. S4 A and Supplementary Methods for additional benchmarking. B Gene-wise correlation between the inferred (y-axis) and measured (x-axis) expression, comparing CMOT with MOFA + and Seurat. Dots: Genes; Numbers: Gene numbers above and below the dotted line. P-values are calculated by a one-sided Wilcoxon rank-sum test (Additional File 1: Table S21). C CMOT inferred normalized gene expression trend (y-axis) across treatment hours (x-axis). Key genes: PER1 and BIRC3 [23,24,25] are markers for glucocorticoid receptor (GR) activation seen later in treatment (3 h). ZSWIM6 [26] is a key gene of early events of DEX treatment (0 h, 1 h) (see Additional File 2 for top 100 highly predictive genes). D Enriched terms associated with CMOT inferred gene expression using 435 genes with a higher gene-wise Pearson correlation compared to MOFA+ ’s 748 genes (B, Additional File 1: Fig. S6B). E The measured (x-axis) versus inferred normalized expression (y-axis) of genes (dots) for three select cells. r is the Pearson correlation coefficient. p is the correlation p-value