Fig. 2: Transcriptome-wide predictability changes with age across tissues.

a, Computational approach used to identify predictability changes with age. Predictability is quantified as the Spearman correlation between the observed expression patterns (in the original data) and the predicted expression patterns (in the reconstructed data), corresponding to the expected pattern given the expression of regulatory neighbors. A high correlation indicates that the expression pattern of a gene fits the regulatory relationships captured by the model (top left), whereas a low correlation indicates the opposite. Predictability is quantified for groups of samples at six different age groups: the decades spanning 20–29 to 70–79. For each gene, predictability is modeled as a linear function of age. b, Distribution of P values for the regression of predictability values within each age group against the mean age of the age group. P values correspond to the two-sided t-test on regression coefficients, without multiple testing correction. Red line: P value distribution obtained from the real data. Gray background: average P value distribution across 100 permutations of the age groups. Black lines: five individual permutations randomly picked from the background. The dashed vertical line indicates the highest P value among the genes considered statistically significant in each tissue (orange and blue bars in e). The number of genes included in each tissue-specific analysis can be found in Supplementary Table 3. c, Heatmap of the predictability slopes across all 370 genes, independently of significance level, ordered by increasing average predictability across tissues. Only the 370 genes for which the regression analysis was performed in all eight tissues were included—that is, the genes with a high average predictability in all eight tissues (Supplementary Table 3). d, Hallmark gene sets enriched in age-related gene–gene relationship changes, captured by GSEA. The heatmap shows all hallmarks with statistically significant (FDR < 0.05) enrichment in at least one tissue. e, Number of genes with predictability increase (blue) and decrease (orange) among the top 100 most significant genes per tissue. ***FDR < 0.001; **FDR < 0.01; *FDR < 0.05; ^.FDR < 0.1. FDR, false discovery rate.