Fig. 5. Lifespan-extending interventions increased proteomic profile conservation of specific modules potentially through cap-independent translation.
a–g Differential Rank Conservation (DIRAC) analysis of the LC-M001 and LC-M004 proteomics data (a–c, e, f) or DIRAC comparison analysis between the LC-M001 proteomics and M001-related transcriptomics data (d, g) using Gene Ontology Biological Process (GOBP)-defined modules (see Supplementary Data 7 (a–c, e, f) or 6 (d, g) for complete results, respectively). Control-1: control for Acarbose, 17α-Estradiol, and Rapamycin; Control-2: control for 4EGI-1. a Overall distribution of module rank conservation index (RCI). Data: median (center line), 95% confidence interval (CI) around median (notch), [Q1, Q3] (box limits), [xmin, xmax] (whiskers), where Q1 and Q3 are the 1st and 3rd quartile values, and xmin and xmax are the minimum and maximum values in [Q1 − 1.5 × IQR, Q3 + 1.5 × IQR] (IQR: the interquartile range, Q3 − Q1), respectively; n = 153 modules. ***P < 0.001 by two-sided Mann–Whitney U-tests after the Benjamini–Hochberg adjustment across four comparisons. b, e Venn diagram of the modules that exhibited (1) the significant intervention effect on module mean of RMSs under 4EGI-1 rank consensus (Analysis of Variance (ANOVA) after the Benjamini–Hochberg adjustment across 306 (153 modules × two rank consensus) tests) and (2) significantly lower (b) or higher (e) mean of RMSs in intervention group than control group (i.e., dissimilarly (b) or similarly (e) changed module to the 4EGI-1 group; the post hoc two-sided Welch’s t-tests after the Benjamini–Hochberg adjustment across six (three comparisons × two rank consensus) comparisons). c, d, f, g Sample rank matching score (RMS) distributions for an example of the dissimilarly tightened modules (c, d; GO:0044794, positive regulation by host of viral process) or the similarly tightened modules (f, g; GO:0006102, isocitrate metabolic process). Dashed line in c and f indicates the mean of RMSs for the rank consensus group (i.e., RCI). Data: the mean (dot) with 95% CI (bar); n = 8 (Control-2, 4EGI-1), 12 (the others) mice. *P < 0.05, **P < 0.01, ***P < 0.001 by two-sided Welch’s t-tests after the Benjamini–Hochberg adjustment across six (three comparisons × two rank consensus; c, f) or four (two comparisons × two omics datasets; d, g) comparisons.