Thermodynamic Operating Constraints of Mammalian Somatic Cell Architecture Classes — GAPE Validation Package

This repository contains the complete validation package for the paper "Thermodynamic Operating Constraints of Mammalian Somatic Cell Architecture Classes: A First-Principles Derivation from DNA Methylation Maintenance Information Costs" (Mahaffey 2026, preprint April 2026). What this work claims Every mammalian somatic cell class has a minimum thermodynamic cost for maintaining its epigenomic identity through cell division. This cost is derived from the Landauer principle applied to DNMT1-mediated CpG methylation maintenance at physiological temperature — the same first-principles thermodynamic law that governs information erasure in any physical system. The minimum cost defines a class-specific Shannon entropy floor, H_min, below which no cell of that architectural type can sustain its identity. The ratio of a cell's observed methylation entropy to that floor is a single dimensionless index — the A-score. In health, A ≈ 1.0. Cancer is a measurable departure from it. The detection threshold A > 1.05 was derived entirely from what healthy cells require. No cancer data was used to set it. Validation results G-002 MCMC: H_min posteriors for all 8 architecture classes validated against 37 published reference cell measurements. 5 independent emcee chains, R-hat < 1.001 for all 8 parameters, 800,000 posterior samples. Principal discovery: immune class correction from 0.795 to 0.8389 ± 0.004 (6.44σ tension resolved by neutrophil reference data). G-008 zero-free-parameter cancer prediction: A_tumor > A_normal correctly predicted for 27 of 28 TCGA cancer types across 4,304 matched tumor-normal pairs. Zero free parameters. No cancer data in the framework. TGCT architectural inversion (A_tumor < A_normal) predicted and confirmed. DCIS stratification: physics-derived threshold sits between low-grade DCIS (A = 1.045, below threshold) and high-grade DCIS (A = 1.101, above threshold) with zero cancer training data. Alzheimer's disease: terminal-class A-score elevation confirmed in De Jager 2014 (n=740, ROSMAP cohort) and Shireby 2022 (n=631, BDR cohort). Signal is 20–40× smaller than GBM — same floor, different failure mode. E(a_bio) activation function: fit to published DunedinPACE age-stratified data recovers biological actualization ceiling t_max = 120.3 ± 7.1 years, consistent with the Gompertz-Makeham human lifespan limit. n_bio ordering: Spearman ρ = 0.905 (p = 0.002) between engine estimates and published Seahorse OCR/ECAR data across 8 architecture classes. Files included Mahaffey_2026_cell_thermodynamics.pdf — preprint paper Mahaffey_2026_cell_thermodynamics.tex — LaTeX source gape_mcmc_g002.py — H_min MCMC validation (G-002) gape_mcmc_g008.py — zero-free-parameter cancer prediction (G-008) gape_mcmc_nbio_ordering.py — metabolic sensitivity ordering test gape_mcmc_e_a_bio.py — DunedinPACE activation function fit fig_thermodynamic_validation.py — figure generation script fig_thermodynamic_validation.png — validation figure evidence_summary.json — master evidence database with full provenance evidence_summary.tsv — flat table for statistical analysis README.md — evidence database documentation Reproducibility Every result in the paper is reproducible by cloning the GitHub repository and running the labeled script. All beta values are drawn from publicly available primary sources cited in the scripts and paper bibliography. Provenance hashes for each data entry are included in the evidence database. Relationship to IAM cosmological framework This work is a biological application of the Informational Actualization Model (IAM), an independent cosmological research program applying Landauer's principle universally across physical scales. The IAM cosmological validation package is archived separately at Zenodo DOI: 10.5281/zenodo.18702042. The biological and cosmological applications are independent — the cell paper stands on its own empirical validation and does not require the cosmological work to be evaluated. Patent status The analytical methodology is protected under U.S. Provisional Patent Applications 64/012,720 (filed March 21, 2026) and 64/014,568 (filed March 23, 2026). The derived results and biological tools are released as open science with no commercial restriction on research use. Keywords DNA methylation, Shannon entropy, Landauer principle, epigenomic fidelity, cell architecture, thermodynamics of information, MCMC, cancer detection, Alzheimer's disease, biological aging, GAPE, IAMPerformance