Wayfinder

Wayfinder is a hypothesis referee. Literature-based discovery (LBD) overproduces hypotheses and tests almost none — the critique that has dogged the field for decades. Wayfinder answers it: it pairs LBD generation with a deterministic referee that tests each machine-generated gene→program→disease hypothesis against a genome-scale CRISPRi Perturb-seq resource, and returns a verdict with a receipt at every hop — including a confident, receipt-backed "no." A failed knockdown comes back untested, not a false negative: an artifact caught, not a discovery missed. The whole loop ran inside Claude Science, whose independent reviewer model flagged and cut the project's own overclaims. On the Marson lab's CD4+ T-cell Perturb-seq data, 22,039 hypotheses were culled to a small set of receipt-backed candidates; the standout — NAB2→Th1/Th2→atopic eczema — is a connection the literature had never drawn (the eczema label is a genetic-association nomination). Measured as a predictor on held-out post-2016 links, the method returns a null at its primary metric — reported straight. Why it matters: it makes machine-generated hypotheses triage-able and trustworthy — every claim carries an experimental receipt, and the system is willing to abstain and to refute.

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