Post-hoc improvement after the pre-registered v1 recovery test failed.
Two changes, diagnosing v1's failure:
- score on the full 12,328-gene LINCS space (week2_lincs_extract.py),
lifting signature overlap from 12% to 85% (brings erythroid markers in)
- src/scoring.py: KS connectivity + per-drug specificity z-score
(spec_z = SDs below a 1,000 random-query null). Primary ranking is
now spec_z. (Textbook tau saturated at +/-100 for a coherent query —
documented; needs a reference-signature library, a v2 item.)
- week3_scoring.py: spec_z primary + WTCS reference + prior-blended
- tests: tau/spec_z calibration test; 19 passing
- scripts/exp_genespace.py: the BING vs all-12,328 comparison
Result: hydroxyurea recovers (rank 40 -> 18, top 6%, passes top-10%),
confirming the v1 failure was the landmark bottleneck not the algorithm.
Overall STILL FAILS: L-glutamine does not reverse (rank 213, metabolite),
and negative controls (norethindrone, ciprofloxacin) rank top-3 —
connectivity != therapeutic relatedness. v1.1 is post-hoc/exploratory,
not a confirmatory test; reported as such in recovery_test_report.md.
Co-Authored-By: Claude Opus 4.8 (1M context) <noreply@anthropic.com>
Run the formal recovery test against the pre-registered criteria and
write the deliverable report (PLAN §6 Week 4):
- week4_recovery_test.py: evaluate hydroxyurea/L-glutamine + 5
pre-specified negative controls vs the committed criteria
- recovery_test_report.md: methodology, FAIL result with diagnosis,
top-10, lisinopril as the non-obvious candidate, limitations, v2
- known_limitations.md: L-glutamine coverage resolved, 12%-overlap
driver, recovery outcome table
Outcome: FAIL on all 3 criteria (hydroxyurea top 13%, L-glutamine
WTCS=0, 1/5 negative controls bottom-half). Root cause is signature/
assay data limitations (lost erythroid+HbF axis, 12% landmark overlap),
not the matching algorithm — reported straight per the project ethos.
Co-Authored-By: Claude Opus 4.8 (1M context) <noreply@anthropic.com>
