genetic_drift
I used the genome-scale CD4+ T-cell Perturb-seq atlas from Marson/Pritchard labs as an empirical genotype-phenotype map to ask how the architecture of the T-cell gene regulatory network shaped which Neanderthal variants
Core trick
Tests whether Perturb-seq regulator centrality predicts introgression frequency, using a matched null with a measured introgression-desert covariate instead of gene density.
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Description
I used the genome-scale CD4+ T-cell Perturb-seq atlas from Marson/Pritchard labs as an empirical genotype-phenotype map to ask how the architecture of the T-cell gene regulatory network shaped which Neanderthal variants survived in modern humans. Introgression frequencies came from the Li et al. 2024 IBDmix map across 1000 Genomes populations.
I set out expecting a clean enrichment story, i.e. that strong T-cell regulators would carry excess archaic ancestry, and I got the opposite. After a properly matched null (constraint, gene length, local gene density, and a directly-measured "introgression desert" covariate replacing a gene-density proxy), the regulator effect is indistinguishable from zero at every resolution tested. Network topology metrics were directionally consistent with hub constraint but statistically redundant with the desert, which inverts the usual reading: the desert is not a nuisance confound but the integral of the genotype-phenotype map: the stabilizing-selection imprint of 50,000 years, consistent with theoretical work.
Why it matters: it is a worked example of network-conditioned mutation-effect theory tested on real data, and an honest one: several hypotheses (context-dependence, three-way viral convergence, epistatic co-introgression) were tested and did not survive their controls, and the manuscript says so. The negative results constrain the field's expectations, and the 151 leads are a concrete, testable hypothesis set for follow-up.
README excerpt
# Network Architecture Conditions the Evolutionary Fate of Archaic Introgression in Human CD4⁺ T Cells > An empirical test of network-conditioned mutation effects on introgressed variation **Hackathon:** Built with Claude: Life Sciences (July 7–13, 2026) **Track:** Research **Author:** Alexandre Gouy (AlgoLife, France) **Dataset:** T-cell Perturb-seq (Marson & Pritchard labs, Gladstone/Stanford) --- > **⚠️ Disclaimer.** This is an experimental research project produced during the [Built with Claude: Life Sciences](https://cerebralvalley.ai/e/built-with-claude-life-sciences) hackathon (July 7–13, 2026). Most of the material — analysis code, figures, literature reviews, manuscript draft, and the *What Remains* resource — was generated using [Claude Science](https://science.anthropic.com). The work has not been extensively reviewed and should be treated as a work in progress. Results, claims, and citations may contain errors. See [Next steps](#next-steps) for what remains to be verified. ## Scientific question How does the architecture of the CD4⁺ T-cell gene regulatory network condition which archaic (Neanderthal/Denisovan) variants survived in modern humans? We use a genome-scale Perturb-seq atlas as an empirical genotype-phenotype map to test whether network topology predicts introgression patterns — and whether the "introgression desert" is a consequence of the GP map rather than an independent confound. ## Three predictions, three results 1. **Hub constraint.*