Fig. 6: scMORE reveals sex-dependent aging-relevant eRegulons associated with PD in neurons.
a, Scatter-plot showing 22 aging-relevant eRegulons significantly associated with PD in neurons (Ns). Each dot represents an eRegulon, with the −log-transformed GRS P values (−log10(P)) shown on the y axis and the −log-transformed CTS P values (−log10(P)) shown on the x axis. Gray dots denote nonsignificant eRegulons, while red dots indicate significant eRegulons. The 22 aging-relevant eRegulons are highlighted in the boxed area. b, Representative examples exhibiting differential activity of three aging-related eRegulons across the young (n = 9), aged (n = 8) and PD groups (n = 14). A two-sided Wilcoxon test was used to assess statistical significance. Boxplot shows the median (center line), IQR (box) and 1.5 × IQR bounds (whiskers). Minima and maxima are represented by the whiskers. Outliers are shown as individual points. c, Heatmap displaying the top-ranked PD-associated eRegulons identified by scMORE across seven brain cell types. d, Representative examples of differential activity of four aging-relevant eRegulons across the young (n = 9), aged (n = 8) and PD groups (n = 14), stratified by sex (male: n = 21; female: n = 10). The two-sided Wilcoxon test was used to assess statistical significance. Boxplot shows the median (center line), IQR (box) and 1.5 × IQR bounds (whiskers). Minima and maxima are represented by the whiskers. Outliers are shown as individual points. e, Functional enrichment analyses of the BCL11A-eRegulon (n = 46 genes) based on GO BP using WebGestalt. f, Regulatory network of the BCL11A and ZEB1 eRegulons that contain PD-associated genes and risk SNPs (SNPs and corresponding P values from GWAS summary data; no multiple correction).
