# PESTO (Prior Evidence Status from Text and Ontologies)

Rare-variant studies now yield more significant gene-phenotype associations than teams can place against prior evidence, and that placement has become the tighter bottleneck. PESTO combines large language model literature curation with structured Open Targets genetic evidence in one agentic pipeline that assigns Novel, Hypothesized, Existing or Established with supporting citations. Across 940 unique associations from two rare-variant studies, 7% were called Novel and 21% Hypothesized; 86% of 50 randomly paired negative controls fell into those two tiers.

Rare-variant studies now yield more significant gene-phenotype associations than teams can place against prior evidence, and that placement has become the tighter bottleneck. PESTO combines large language model literature curation with structured Open Targets genetic evidence in one agentic pipeline that assigns Novel, Hypothesized, Existing or Established with supporting citations. Across 940 unique associations from two rare-variant studies, 7% were called Novel and 21% Hypothesized; 86% of 50 randomly paired negative controls fell into those two tiers.