Fig. 4: GSEA and URA of FC- and EXT-associated differential expression across sexes.

a–c GSEA was used to test concordance of differential gene expression analyses results with gene expression signatures from the Molecular Signatures Database. Enrichment scores are calculated against background and they are also corrected for multiple comparisons based on FDR. Summarizing the GSEA results, the Venn diagram revealed unique, and shared positively (red ellipse) and negatively enriched (blue ellipse) gene sets in FC or EXT compared to TA in both sexes (a), while the bubble plots depict the uniquely FC-enriched gene sets (b), and uniquely EXT-enriched gene sets (c) with the lowest p value (top 20). Gene sets with negative normalized enrichment score (NES) are depicted with blue circles, while those with positive NES with red circles. The size of the circles corresponds to number of underlying DEGs. d DEGs together with their fold changes were used for the prediction of activation/deactivation of upstream regulator by URA based on Fisher’s exact test p value and activation z-score. Bubble plot for the significant FC- or EXT-associated upstream regulators based on DEGs or genes of differentially expressed modules uniquely associated with FC and EXT, respectively. Upstream regulators with negative z-score are depicted with blue circles, while those with positive z-score with red circles. The size of the circles corresponds to number of underlying DEGs. The predictions of CREB1 activity are highlighted with a red box.