{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T21:08:24Z","timestamp":1779484104983,"version":"3.53.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health & Welfare, Republic of Korea","award":["RS-2025-02303925"],"award-info":[{"award-number":["RS-2025-02303925"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korea government","award":["RS-2025-16652968"],"award-info":[{"award-number":["RS-2025-16652968"]}]},{"name":"Korea University BK21 FOUR Academic Writing"},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2009=\u200950 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\u2013473). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>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)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag300","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:46:53Z","timestamp":1778154413000},"source":"Crossref","is-referenced-by-count":0,"title":["IDAP: an integrated literature- and knowledge-graph-driven evidence prioritization pipeline for precision oncology"],"prefix":"10.1093","volume":"42","author":[{"given":"Yebin","family":"Ryu","sequence":"first","affiliation":[{"name":"Department of Integrated Biomedical and Life Science, Korea University , Seoul, 02841,","place":["Republic of Korea"]},{"name":"L-HOPE Program for Community-Based Total Learning Health Systems, Korea University , Seoul, 02841,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha-Eun","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Integrated Biomedical and Life Science, Korea University , Seoul, 02841,","place":["Republic of Korea"]},{"name":"Korea University National Research Laboratory for Convergence Degradation Biology, , Seoul, 02841,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8839-6297","authenticated-orcid":false,"given":"Joon-Yong","family":"An","sequence":"additional","affiliation":[{"name":"Department of Integrated Biomedical and Life Science, Korea University , Seoul, 02841,","place":["Republic of Korea"]},{"name":"L-HOPE Program for Community-Based Total Learning Health Systems, Korea University , Seoul, 02841,","place":["Republic of Korea"]},{"name":"Korea University National Research Laboratory for Convergence Degradation Biology, , Seoul, 02841,","place":["Republic of Korea"]},{"name":"College of Health Science School of Biosystem and Biomedical Science, , Korea University, Seoul, 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"2026052216592151400_btag300-B1","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1002\/ajh.25125","article-title":"Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials","volume":"93","author":"Bussel","year":"2018","journal-title":"Am J Hematol"},{"key":"2026052216592151400_btag300-B2","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The cancer genome atlas Pan-Cancer analysis project","volume":"45","author":"Cancer Genome Atlas Research Network","year":"2013","journal-title":"Nat Genet"},{"key":"2026052216592151400_btag300-B3","doi-asserted-by":"publisher","first-page":"264","DOI":"10.3322\/caac.21825","article-title":"Interpreting and integrating genomic tests results in clinical cancer care: overview and practical guidance","volume":"74","author":"Casolino","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"2026052216592151400_btag300-B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/PO.17.00011","article-title":"OncoKB: A precision oncology knowledge base","volume":"2017","author":"Chakravarty","year":"2017","journal-title":"JCO Precis Oncol"},{"key":"2026052216592151400_btag300-B5","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13073-017-0424-2","article-title":"Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden","volume":"9","author":"Chalmers","year":"2017","journal-title":"Genome Med"},{"key":"2026052216592151400_btag300-B6","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1182\/blood-2009-08-236471","article-title":"Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia","volume":"115","author":"Friedberg","year":"2010","journal-title":"Blood"},{"key":"2026052216592151400_btag300-B7","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","article-title":"Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer","volume":"173","author":"Hoadley","year":"2018","journal-title":"Cell"},{"key":"2026052216592151400_btag300-B8","doi-asserted-by":"publisher","first-page":"3601","DOI":"10.1038\/s41591-024-03233-x","article-title":"A foundation model for clinician-centered drug repurposing","volume":"30","author":"Huang","year":"2024","journal-title":"Nat Med"},{"key":"2026052216592151400_btag300-B9","doi-asserted-by":"publisher","first-page":"djv253","DOI":"10.1093\/jnci\/djv253","article-title":"Impact of a biomarker-based strategy on oncology drug development: A meta-analysis of clinical trials leading to FDA approval","volume":"107","author":"Fontes Jardim","year":"2015","journal-title":"JNCIJ"},{"key":"2026052216592151400_btag300-B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/PO.18.00213","article-title":"Use of a targeted exome next-generation sequencing panel offers therapeutic opportunity and clinical benefit in a subset of patients with advanced cancers","volume":"3","author":"Kopetz","year":"2019","journal-title":"JCO Precision Oncology"},{"key":"2026052216592151400_btag300-B11","doi-asserted-by":"publisher","first-page":"D1230","DOI":"10.1093\/nar\/gkac979","article-title":"CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase","volume":"51","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2026052216592151400_btag300-B12","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s40487-017-0055-1","article-title":"Current status and study progress of recombinant human endostatin in cancer treatment","volume":"6","author":"Li","year":"2018","journal-title":"Oncol Ther"},{"key":"2026052216592151400_btag300-B13","doi-asserted-by":"publisher","first-page":"3921","DOI":"10.1016\/j.cell.2023.07.014","article-title":"Pan-cancer proteogenomics connects oncogenic drivers to functional states","volume":"186","author":"Li","year":"2023","journal-title":"Cell"},{"key":"2026052216592151400_btag300-B14","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.annonc.2021.02.006","article-title":"High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types","volume":"32","author":"McGrail","year":"2021","journal-title":"Ann Oncol"},{"key":"2026052216592151400_btag300-B15","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1007\/s00280-013-2091-3","article-title":"A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas","volume":"71","author":"Park","year":"2013","journal-title":"Cancer Chemother Pharmacol"},{"key":"2026052216592151400_btag300-B16","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/1477-7819-10-170","article-title":"Systematic review and meta-analysis of endostar (rh-endostatin) combined with chemotherapy versus chemotherapy alone for treating advanced non-small cell lung cancer","volume":"10","author":"Rong","year":"2012","journal-title":"World J Surg Oncol"},{"key":"2026052216592151400_btag300-B17","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev-genom-090413-025552","article-title":"Translating genomics for precision cancer medicine","volume":"15","author":"Roychowdhury","year":"2014","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2026052216592151400_btag300-B18","doi-asserted-by":"publisher","first-page":"D20","DOI":"10.1093\/nar\/gkae979","article-title":"Database resources of the national center for biotechnology information in 2025","volume":"53","author":"Sayers","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"2026052216592151400_btag300-B19","doi-asserted-by":"publisher","first-page":"10164","DOI":"10.1038\/s41467-024-54434-4","article-title":"Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment","volume":"15","author":"Song","year":"2024","journal-title":"Nat Commun"},{"key":"2026052216592151400_btag300-B20","doi-asserted-by":"publisher","first-page":"6373","DOI":"10.1158\/1078-0432.CCR-12-1627","article-title":"Personalized medicine in a phase I clinical trials program: the MD Anderson cancer center initiative","volume":"18","author":"Tsimberidou","year":"2012","journal-title":"Clin Cancer Res"},{"key":"2026052216592151400_btag300-B21","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/s41588-020-0603-8","article-title":"A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer","volume":"52","author":"Wagner","year":"2020","journal-title":"Nat Genet"},{"key":"2026052216592151400_btag300-B22","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1056\/NEJMsa1012065","article-title":"The ClinicalTrials.gov results database\u2014update and key issues","volume":"364","author":"Zarin","year":"2011","journal-title":"N Engl J Med"},{"key":"2026052216592151400_btag300-B23","doi-asserted-by":"publisher","first-page":"D1180","DOI":"10.1093\/nar\/gkad1004","article-title":"The ChEMBL database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods","volume":"52","author":"Zdrazil","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2026052216592151400_btag300-B24","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/nm.4333","article-title":"Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients","volume":"23","author":"Zehir","year":"2017","journal-title":"Nat Med"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btag300\/68261073\/btag300.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/42\/5\/btag300\/68261073\/btag300.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/42\/5\/btag300\/68261073\/btag300.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T20:59:28Z","timestamp":1779483568000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btag300\/8675120"}},"subtitle":[],"editor":[{"given":"Virginie","family":"Uhlmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,3]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btag300","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,5]]},"article-number":"btag300"}}