IDAP: an integrated literature- and knowledge-graph-driven evidence prioritization pipeline for precision oncology.

Abstract

Advances in tumor sequencing enable routine detection of dozens to hundreds of somatic alterations per patient, yet only a minority can be linked to established therapeutic evidence. Curated resources such as OncoKB provide high-quality variant-drug annotations but remain limited in coverage, particularly for rare or low-frequency variants. This coverage gap motivates computational frameworks that can integrate curated, literature-derived, graph-based, and clinical-trial evidence to prioritize therapeutic hypotheses for expert review. We developed the Integrated Drug Annotation Pipeline (IDAP), a modular framework that combines four complementary evidence streams: curated variant-drug associations from OncoKB, literature-derived gene-drug mention counts from PubMed abstracts, graph-based drug prioritization using a TxGNN-derived biomedical knowledge graph, and cancer-specific clinical-trial evidence from ClinicalTrials.gov. Given a cancer type and a MAF file, IDAP generates patient-level reports summarizing detected variants, ranked therapeutic hypotheses, supporting evidence layers, and relevant clinical trials. Evaluated across five cancer types (n = 50 samples), IDAP expanded evidence-linked therapeutic hypotheses beyond curated databases alone. Among patients without OncoKB recommendations (26/50), IDAP identified a median of 87 candidate drugs (range: 2-473). To reduce cross-source scale imbalance, the final ranking used within-sample percentile normalization with fixed bonuses for curated evidence, multi-source support, and trial linkage. Under this revised ranking, 24/50 top-ranked candidates were supported by at least two evidence sources and 44/50 had associated ClinicalTrials metadata. In an exploratory external CIViC comparison, IDAP recovered at least one matched CIViC-supported therapy in 28/41 eligible samples, with 13/41 appearing within the top 10 candidates. These outputs are intended to support evidence triage and translational interpretation rather than direct treatment recommendation. IDAP is freely available at https://github.com/joonan-lab/IDAP-pipeline, with full documentation at https://joonan-lab.github.io/IDAP-pipeline. An archived snapshot of the code used in this study is deposited on Zenodo (DOI: https://doi.org/10.5281/zenodo.19301367).