The chief dawgs
Built at Built with Claude: Life Sciences · Jul 7, 2026 · Remote

We investigated whether a genome-scale CD4+ T-cell Perturb-seq screen contains reproducible regulatory architecture beyond ranked hits, statistical noise and connectivity hubs We built a quality-audited regulator × gene × condition operator from a 1.8 TB public CRISPRi atlas using a laptop-scale pipeline. Spectral denoising reduced the operator to 92 empirically supported signal directions, and consensus community detection revealed structure 259 standard deviations above a matched null The strongest result was annotation-blind recovery of mitochondrial Complex I, identified only after clustering, at BH-FDR 1.4 × 10⁻⁷. A second SAGA-centered module was supported by convergent evidence across CORUM, tensor factors and an independent K562 screen, while cross-cell-type analysis across CD4, K562 and RPE1 separated universal from T-cell-specific regulation We also tested the predictive boundary of this structure. Real and shuffled regulator features performed identically for leave-regulator-out prediction, showing that recoverable structure does not imply inductive predictability The result is an open, reproducible analysis and manuscript that others can build on