Direction Instability: A Magnitude-Invariant Metric for Cross-Cell-Line Drug Mechanism Transport

Direction instability (DI) scores and validation data for 8,949 drugs from the LINCS L1000 Connectivity Map (978 landmark genes, 167,266 signatures). DI quantifies the directional consistency of a drug's transcriptomic effects across cell lines (DI = 1 - mean pairwise cosine similarity of unit-normalized signatures). Because DI operates on normalized directions, it is invariant to effect magnitude by construction. Biological validity is established through three independent non-cosine channels: Jaccard gene-set overlap (AUROC = 0.957), CCLE target expression breadth (p = 1.1e-5), and PRISM viability concordance (p = 0.019). The scorer and validation labels were frozen under pre-registered commit SHAs (1dc20a2 and 43d7f8a) before any real data were analyzed. This deposit contains per-drug DI scores with population-null p-values (JSON), leave-one-out holdout predictions (JSON), geometric validity test results and plots (JSON/PNG), pre-registration documents (frozen before analysis), and the analysis codebase (Python).