The Public Repurposing Index (PRI) 2.0 Strategic Enhancement and Operational Roadmap for Regulatory-Grade AI Drug Discovery
Abstract
The Public Repurposing Index (PRI) 2.0 Strategic Enhancement and Operational Roadmap for Regulatory-Grade AI Drug Discovery AuthorBrewtanius Ink LLC · The CollectiveOS- Immortal Tek Abstract The Public Repurposing Index (PRI) 2.0 transforms a general data aggregator into a regulatory-grade hypothesis engine for rare-disease drug repurposing. Grounded in the BioLink Model for semantic interoperability, PRI consolidates curated evidence into a transparent knowledge graph compatible with federal research ecosystems. A geometric, rewired heterogeneous GNN—augmented by zero-shot ranking—prioritizes repurposing candidates and returns explainable rationales via Captum/GNNExplainer. PRI’s Context of Use (COU) is scoped to support preclinical prioritization and non-binding patient stratification proposals; outputs are accompanied by a credibility plan aligned to the FDA’s model-credibility framework, a digital thread from source data to receipt, calibration and uncertainty reporting, and continuous monitoring. A pilot on GSD1b (ORPHA:365) uses empagliflozin as a retrospective positive control and preregisters prospective hypotheses for expert adjudication. Emphasizing openness, metabolic specialization, and a public-utility funding posture, PRI 2.0 delivers auditable AI: not only ranked candidates, but a defensible evidence trail regulators and clinicians can evaluate. Executive Summary Problem. More than 30 million Americans live with one of 7,000+ rare diseases; roughly 95% lack an…
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