ATRA and ATO exert synergistic effects on controlling SEPRTs in APL cells. (A) Clustering of SEPRTs after ATRA or ATO treatment using self-organizing map. The left panel shows 3 gene clusters color-coded on the map, with per-hexagon genes labeled (for example, genes in the insert with heatmap showing expression pattern). The right panel shows that each presentation indicates treatment- and time-specific changes, in which upregulated (red), downregulated (blue), and no changed (light yellow) genes are well separated. FC, fold change. (B) Functional enrichments in gene clusters. Gene Ontology Biological Process terms were used for enrichment analysis based on the Fisher exact test (1 sided), with odds ratios and 95% confidence interval calculated. FDR, false discovery rate. (C) Pathway crosstalk identified from integrative analysis of time course expression data and known pathway interaction data. The crosstalk illustrated in the same layout but nodes (genes) colored and sized in a treatment- and time-specific manner. Current approved drug therapeutics for crosstalk genes based on the ChEMBL database. ATC, anatomical therapeutic chemical; FDA, US Food and Drug Administration.