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Author SHA1 Message Date
fd4591949c Week 3: CMap connectivity scoring engine + ranked candidates
Implement the matching engine (PLAN §6 Week 3):
- src/scoring.py: weighted-KS/GSEA enrichment, weighted connectivity
  score (WTCS, Lamb 2006 / Subramanian 2017), signed NCS normalization,
  rank_drugs, and a sickle-pathway mechanistic prior
- tests/test_scoring.py: real reference tests for the scorer (perfect
  reversal<null<mimic, same-sign->0, absent-gene invariance) + prior
- week3_scoring.py: score 300 drugs -> ranked_candidates_v1.csv with a
  raw ranking and a secondary mechanistic-prior-weighted ranking

Preliminary (formal recovery test is Week 4): hydroxyurea raw rank
40/300 (top 13%, just misses pre-registered top-10%), blended rank 7;
L-glutamine WTCS=0 (ambiguous). Notably anti-inflammatory SCD drugs
cluster in the raw top tier — the engine reverses the inflammation axis,
not the erythroid axis, traceable to the 12% landmark-overlap caveat.

Co-Authored-By: Claude Opus 4.8 (1M context) <noreply@anthropic.com>
2026-06-23 22:34:56 +02:00