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Week 2: 300-drug profiles with LINCS signatures + ChEMBL

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Build the drug profile dataset (PLAN §6 Week 2):
- week2_curate_drugset.py: 300-drug set (2 ground-truth + 32 related-
  mechanism + 26 negative-control + 240 random), restricted to
  LINCS-scorable compounds, seed=42
- week2_chembl.py: InChIKey->ChEMBL match (145/300), MoA + targets
- week2_lincs_extract.py: cmapPy-slice both Level-5 GCTX phases to 978
  landmark genes, mean-aggregate per drug to one consensus signature
- week2_assemble.py: join into drug_profiles_v1.parquet, Tier B (LINCS
  single-source), scored flag per PLAN §6 Week 3 task 2
- docs/data_sources.md: drug set composition + LINCS/ChEMBL provenance

Results (all gitignored data): 300/300 drugs scored, both ground-truth
drugs present (hydroxyurea Phase II = CHEMBL467, L-glutamine Phase I).
Key caveat recorded: only 56/477 (12%) of the disease signature genes
are LINCS landmarks, so Week-3 scoring uses a 30-up/26-down query.

Co-Authored-By: Claude Opus 4.8 (1M context) <noreply@anthropic.com>
This commit is contained in:
Junior B.
2026-06-23 22:25:00 +02:00
parent c7b6649d31
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docs/data_sources.md
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| OMIM | https://omim.org | Free for academic | License for commercial | Disease genetics | TBD | TBD |
| GEO (GSE35007) | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35007 | GEOparse, FTP | Public domain | Disease signature (study 1) | GPL10558 | 2026-06-23 |
| GEO (GSE16728) | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16728 | GEOparse, FTP | Public domain | Disease signature (study 2) | GPL570 | 2026-06-23 |
| ChEMBL | https://www.ebi.ac.uk/chembl | Python client, bulk SQLite | CC BY-SA 3.0 | Drug structures, targets | TBD | TBD |
| LINCS L1000 | https://clue.io/data | Bulk download | Restricted academic free | Drug expression signatures | TBD | TBD |
| ChEMBL | https://www.ebi.ac.uk/chembl | chembl_webresource_client | CC BY-SA 3.0 | Drug structures, MoA, targets | API (live) | 2026-06-23 |
| LINCS L1000 Phase I | GSE92742 (GEO) | GEOparse/FTP + cmapPy | CC0 (GEO) | Drug signatures (incl. L-glutamine) | GSE92742 | 2026-06-23 |
| LINCS L1000 Phase II | GSE70138 (GEO) | GEOparse/FTP + cmapPy | CC0 (GEO) | Drug signatures (incl. hydroxyurea) | GSE70138 | 2026-06-23 |
| ClinicalTrials.gov | https://clinicaltrials.gov | API | Public domain | Trial history | TBD | TBD |
| FDA DailyMed | https://dailymed.nlm.nih.gov | API | Public domain | Approved labels | TBD | TBD |
| Reactome | https://reactome.org | API, bulk | CC0 | Pathway data (Week 3 prior) | TBD | TBD |
@@ -42,6 +43,30 @@ robustness.
Reproduce with `scripts/week1_explore.py` (download + DE + concordance) then
`scripts/week1_finalize.py` (mygene mapping + persist).
## Drug profiles (Week 2)
300-drug set (`drug_set_v1.csv`), composed and restricted to LINCS-scorable compounds:
| Inclusion reason | n | Notes |
|---|---|---|
| ground_truth | 2 | hydroxyurea (Phase II), L-glutamine = "glutamine" (Phase I) |
| related_mechanism | 32 | HbF inducers (decitabine, azacitidine, vorinostat, panobinostat, romidepsin…), NO donors, antioxidants, anti-inflammatories |
| negative_control | 26 | antifungals, antihistamines, antibiotics, hormones |
| general_sample | 240 | random from LINCS catalog, seed=42 |
- **LINCS signatures:** per-drug consensus = mean of Level-5 MODZ z-scores across the drug's
sig_ids (cell lines/doses/times), restricted to the 978 landmark genes. Drawn from BOTH
phases (hydroxyurea is Phase-II-only; L-glutamine is Phase-I-only). All 300 drugs scored.
- **ChEMBL:** matched by InChIKey — 145/300 (curated drugs ~90%, random research compounds
38%, as expected). 43 drugs carry target annotations; 46 carry mechanism-of-action.
- **Tier:** all signature-backed drugs are Tier B (LINCS is a single source → fails Tier A's
not-single-source rule).
- **Signature↔landmark overlap:** only 56/477 (12%) of the disease signature genes are LINCS
landmarks, so connectivity scoring (Week 3) uses a 30-up/26-down query. The erythroid hallmark
genes (CA1, AHSP, SLC4A1, HBG) are NOT landmarks. This is a key limitation for the recovery test.
- Reproduce: `week2_curate_drugset.py` → `week2_chembl.py` → download Level-5 GCTX →
`week2_lincs_extract.py` → `week2_assemble.py`.
## Licensing note for LINCS
Read the LINCS data use terms before commercial use. For the MVP (research / proof-of-concept)