Fig. 6. Chaperones organization is conserved in organ development and brain aging.

a Organ specificity and organ time point specificity of protein-coding genes (16,955 genes) and chaperones (31 core and 156 variable genes). Specificity values ranged between 0 (non-specific expression) and 1 (specific expression). Across organs and time points, chaperones were more ubiquitously expressed than protein-coding genes, and core chaperones were more ubiquitously expressed than variable chaperones. Adjusted p-values for organ specificity and time point specificity in brain, cerebellum, heart, kidney, liver, ovary, and testis, in respective order: chaperones versus protein-coding genes: p = 4.8E−16, 3.24E−18, 7.26E−17, 8.16E−20, 1.48E−14, 3.2E−21, 3.27E−15, 1.9E−20; core versus variable chaperones: p = 5.39E−10, 4.5E−5, 1.4E−4, 2.5E−4, 1.4E−4, 6.44E−5, 3.53E−5, 1.23E−7 (one-sided Mann–Whitney test, Benjamini–Hochberg correction). Chaperones n = 187, 180, 171, 178, 176, 176, 177, 184; protein-coding genes n = 16,955, 14,517, 14,017, 13,828, 14,136, 13,854, 13,988, 15,712; core chaperones n = 31; variable chaperones n = 156, 149, 140, 147, 145, 145, 146, 153. b Expression correlation values in adult tissues for chaperone pairs whose pair-mates share, or do not share, a developmental module. Except for ovary, pairs belonging to the same developmental module were more highly correlated than other pairs. Adjusted p-values for brain, cerebellum, heart, liver, and testis, in respective order: p = 3.14E−14, 6.33E−8, 4.7E−79, 8.6E−27, 3.5E−231 (one sided Mann–Whitney test, Benjamini–Hochberg correction). Pairs in same module n = 916, 1204, 862, 694, 1818; pairs in other modules n = 16,851, 16,563, 16,904, 17,072, 15,948. c Consistency between chaperones that were highly correlated (r > 0.8) in adult brain (n = 2014 pairs) and in aging brain (n = 1193 pairs) is shown by their significant overlap (265 pairs, p = 1.4E−32, one-sided Fisher exact test). The distribution of the 265 consistent chaperone pairs by the number of non-brain tissues in which they were highly correlated reveals that most of them were brain-specific, i.e., were not highly correlated in any other tissue. d The correlation between chaperone expression levels in prefrontal cortex and age is shown for core chaperones (n = 26), variable chaperones that were upregulated in adult brain (n = 78), and variable chaperones that were not upregulated in brain (n = 73, other). Expression levels of core and brain-upregulated chaperones decreased with age. The expression levels of other variable chaperones did not change (see Supplementary Fig. 8B for additional brain regions). The difference between the two subsets of variable chaperones was statistically significant (p = 6.9E−6, one-sided Mann–Whitney test). e Relative expression levels of chaperones in patients with Alzheimer’s disease and controls is shown for core chaperones (n = 26), variable chaperones that were upregulated in adult brain (n = 78), and remaining variable chaperones (n = 73, other). Expression levels of core and brain-upregulated chaperones decreased in patients, whereas expression levels of remaining variable chaperones did not change. The difference between the two subsets of variable chaperones was statistically significant (p = 4.12E−6, one-sided Mann–Whitney test). In the boxplot representation, center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range; points, outliers. Source data are provided as a Source Data file.