Fig. 4: Within-set and between-set regulatory relationships altered with age.

a, Contribution of within-set and between-set correlation changes to age-related predictability changes, represented as the weighted sum of age-related correlation changes between genes with increasing (top) or decreasing (bottom) predictability with age and their regulatory neighbors within (full color) or between (transparent) the same gene set. Correlation changes with age are quantified as the slope of the correlation ~ Age regression. These values are weighted with the coefficients of the regulatory model, so that correlation changes in strongly connected regulatory neighbors (higher coefficient) are prioritized. b,e, Subnetwork of the neighborhood of genes with age-related predictability changes. Nodes represent genes, colored by predictability slope in the respective tissue. Connections between nodes represent gene–gene relationships captured by the regulatory model. b, Neighborhood of LAMTOR5, colored by predictability slope with age in Artery – tibial. e, Neighborhood of ITIH2, colored by predicatability slope with age in Blood. c,f, Correlation between expression of genes with predictability changes (LAMTOR5 in c and ITIH2 in f) and regulatory neighbors across age groups. d,g, Comparison of expression of genes LAMTOR5 (d) and ITIH2 (g) in the original data (observed expression, x axis) and reconstructed expression based on the regulatory neighborhood (predicted expression, y axis). The linear regression fit to the trend is shown along with the 95% confidence interval bands. pred., predicted.