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

ABSTRACT

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.