Extended Data Fig. 6: Multimodal analysis for ovary and breast and up and downregulated functions with age.

A-B Multi-Omics Factor Analysis (MOFA) results for ovary (A) and breast (B): heatmaps show variance explained by 10 latent factors across modalities (bottom) and their correlation with donor age (top). Asterisks denote significance (*FDR < 0.05 & >0.005, **FDR < 0.005 & >0.0005, ***FDR < 0.0005). C Gene set enrichment analysis (GSEA) using Gene Ontology for ranked genes from pseudobulked menopausal-status-differential expression analyses per each myometrial cell type (FDR < 0.05). Bold terms are collagen or extracellular-matrix related terms. D Trajectory of the most weighted feature for Factor 4 in myometrium, showing the difference between low values in young donors (left) and high values in old donors (right); each dot corresponds to a sample; solid line represents locally estimated scatterplot smoothing (LOESS) fitted mean trajectories with 95% confidence intervals around the LOESS estimate (shaded regions). E Spatial gene expression counts of the top-ranked gene MFAP5 in Factor 4 of the uterus, comparing the expression in one peri (left) and one post-menopausal (right) samples. F Gene Set Enrichment Analysis (GSEA) of the top 7 pathways with positive (NES > 0) and negative (NES < 0) normalized enrichment scores using Gene Ontology for the genes contributing to Factor 4 in the uterus. Enrichment significance was assessed using a Kolmogorov-Smirnov-like running-sum statistic (one-sided test), FDR < 0.05.