CRISPR perturbation-direction coherence persists in scGPT's embedding space

Raju defines a perturbation-stability score, the mean cosine similarity between per-cell CRISPR shift vectors and the gene's mean perturbation direction, across 2,200+ perturbations from 5 datasets [raju-2026-geometric-coherence-of-single-cell-crispr-perturbations] In raw PCA space, magnitude-stability correlation is rho=0.75-0.97, with pleiotropic regulators (CEBPA) incoherent and lineage factors (KLF1) coherent [raju-2026-geometric-coherence-of-single-cell-crispr-perturbations] Recomputing the score inside scGPT's pretrained embedding space reproduces the structure (Norman rho=0.935, Dixit 0.712, Replogle 0.851; all p<1e-25) [raju-2026-geometric-coherence-of-single-cell-crispr-perturbations] The coherence is thus a genuine geometric property of the model's representation and predicts unfolded-protein-response activation beyond shift magnitude (p<1e-18) [raju-2026-geometric-coherence-of-single-cell-crispr-perturbations]