§01 — The wedge
Methylation predicts drug response. Nobody has curated it.
Three facts make pharmaco-epigenomics a real, defensible frontier: the signal is proven, the curated resource doesn't exist, and the existing authorities openly contradict each other. Here's the evidence — caveats included.
§02 — The signal is real
Methylation alone predicts cytotoxic drug response.
Across 987 GDSC cell lines and 8 drugs, DNA-methylation-only models reached AUROC up to 0.97 — and transferred to temozolomide response in low-grade glioma patients. The canonical, clinically deployed pharmaco-epigenomic biomarker — MGMT promoter methylation → temozolomide (the Hegi/Stupp glioblastoma lineage) — is the proof that this generalizes from bench to bedside.
§03 — The white space
Two worlds of drug-response data. Neither curates methylation.
MethylGKB owns the empty quadrant: methylation as a first-class, curated, queryable drug-response predictor. And unlike biophysical claims, these come pre-graded — clinical truth here exists and is scored — so the database is validatable by construction.
§04 — Contradiction as signal
When the authorities disagree, that's the data.
The FDA's Table of Pharmacogenetic Associations and CPIC's guidelines cover ~106 vs ~59 drugs, overlap on 39, and are fully concordant on dosing for only 5. Most knowledge bases would force a winner. MethylGKB keeps both as a first-class CONTRADICTS edge — a flag for a hidden conditioning variable nobody has named yet.
§05 — Sources
Verified references
From a deep-research sweep — 23 of 25 claims survived adversarial verification. The two that failed (specific consortium gene-drug counts; an over-strong "no methylation features" claim) are excluded here.