METHYLGKB by Polymer Genomics

§01 — Strata v3 · three structural gates

Start from the molecular state, not the disease.

Start from molecular state, not disease taxonomy. Surface opportunities an expert is structurally unable to reach.

An expert evaluates a handful of taxonomy-shaped hypotheses about genes they already know. Strata evaluates the taxonomy-free, prior-free, confound-controlled space — then validates the survivors in independent screens.

§02 — The three structural gates

Three priors the expert cannot drop.

Each gate is a constraint baked into how the field is trained, funded, and regulated. The agent doesn't out-think the expert inside a gate — it operates without the gate.

§03 — The discovery funnel

17,181 genes → externally replicated.

Every promoter gene enters. Each stage strips a structural prior or demands harder evidence, narrowing an unbiased genome-wide pass to a short list of replicated leads.

§04 — Hero leads

The leads no domain prior would surface.

Each lead is a methylation state whose association with drug response survives tissue + methylome-PC adjustment, is confirmed by functional silencing, and replicates in independent screens. The gene names are the point: these are not the genes an expert would have tested.

§05 — Honesty rails

What this is, and what it isn't.

The caveats are a feature, not a disclaimer. They define the claim precisely enough to be falsifiable.