METHYLGKB by Polymer Genomics

§01 — Pharmaco-epigenomics

Everyone's getting sequenced. Almost no one gets an answer.

Whole-genome sequencing is everywhere — and mostly inert. The actionable layer isn't the sequence you inherited; it's the methylome: the regulatory state your cells are in right now. MethylGKB reads it from a single whole-blood methylation array and turns it into pharmacogenomic insight — what will work, what won't, what's toxic.

Whole-blood methylation readout · chr10 · MGMT promoter window β = 0.00 → 1.00
0.0 — unmethylated 0.5 1.0 — methylated

§02 — The white space

There is no PharmGKB for methylation. We're building it.

Drug-response knowledge splits into two worlds that rarely touch — germline variant guidelines and cancer cell-line screens — and neither curates methylation. The one portal that integrates it isn't a knowledge base. That empty quadrant is the product.

0.97
Best-case AUROC for methylation-only drug-response prediction across 987 GDSC cell lines, transferring to patient temozolomide response.
PLOS ONE 2021
5 / 39
Drugs where the FDA and CPIC fully agree on dosing — out of 39 they share. Two authoritative sources, in open contradiction.
Hertz, AJHP 2022
0
Curated, queryable pharmaco-epigenomic knowledge bases in existence. The field is named but has no operational resource.
Field survey, verified

§03 — Why sequence isn't enough

The genome says who you are. The methylome says what to do about it.

Sequence layer · static

What WGS gives you

A fixed inheritance. Powerful for rare-disease and a handful of germline pharmacogenes — but for most patients it returns variants of uncertain significance and little a clinician can act on today. It can't see regulatory state, environment, or how a cell is actually behaving.

Methylation layer · dynamic

What the methylome gives you

A live regulatory readout from whole blood. Methylation already carries the canonical, clinically deployed drug biomarker (MGMT → temozolomide), predicts cytotoxic response on its own, and changes with disease and exposure. It's the layer where the actionable signal lives — and it's cheap to read.

§04 — What MethylGKB is

A curated knowledge base of methylation → drug-response associations.

Every association is a structured, evidence-graded claim: a methylation locus that predicts response to a drug, with its grade, provenance, and the contradictions it lives among — retained, not smoothed over.

§05 — Where it goes

A knowledge base that grows itself.

MethylGKB sits on Polymer's formal-claims substrate. Contradictions — like FDA vs CPIC — aren't errors to resolve; they're the richest seed. An agent walks the base, finds tensions and gaps, proposes the conditioning variable that reconciles them, verifies each new claim against its own evidence, and integrates it. Knowledge accumulates instead of evaporating.