An Integrated Whole-Body Normal-Tissue Proteomics Framework Maps Tissue Variation in Senescence-Associated and Ferroptosis-Related Protein Programs

Normal-tissue proteomics can contextualize senescence-associated and ferroptosis-related protein programs. We analyzed 580 normal human tissue specimens (466 adult and 114 fetal) representing 9 adult and 8 fetal Patient IDs. After excluding 748 all-missing proteins, 12,861 proteins were retained. The matrix contained 64.28% missing entries. Pathway scoring used 20 stochastic downshift completions as a model-conditional Monte Carlo ensemble, rather than formal multiple imputation. Across 41 adult tissue categories with at least three specimens, the senescence-associated proteomic proxy was highest in gall bladder and bone and lowest in spinal cord. Observed LGALS7, H1-3, MYH2, MYL1, and GFAP patterns largely reflected tissue identity. GPX4 and FTL were broadly detected, whereas SLC7A11 and CTHRC1 were sparsely detected, describing target presence rather than exposure or toxicity. Observed-only Welch diagnostics identified 5030 proteins with Benjamini-Hochberg false-discovery rates below 0.05 among 8497 testable proteins under specimen-independence assumptions. Extensive missingness, incomplete marker coverage, repeated donor sampling, and limited batch-stage overlap constrain developmental and mechanistic interpretation. Independent biological validation is required. Together, these findings provide a tissue-resolved proteomic reference and an accompanying local platform with a traceable analytical workflow for hypothesis generation and selection of follow-up tissues and proteins.