Comparative Analysis of Public Knowledge Bases for Precision Oncology

作者：Steffen Pallarz, Manuela Benary, Mario Lamping, Damian Tobias Rieke, Johannes Starlinger, Christine Sers, David Luis Wiegandt, Marc A. Seibert, Jurica Ševa, Reinhold Schäfer, Ulrich Keilholz, Ulf Leser · 发表于：JCO Precision Oncology · 年份：2019 · DOI：10.1200/po.18.00371 · 被引用次数：68 · 研究领域：Cancer Genomics and Diagnostics、Bioinformatics and Genomic Networks、Genomics and Rare Diseases

PURPOSE: Precision oncology depends on the availability of up-to-date, comprehensive, and accurate information about associations between genetic variants and therapeutic options. Recently, a number of knowledge bases (KBs) have been developed that gather such information on the basis of expert curation of the scientific literature. We performed a quantitative and qualitative comparison of Clinical Interpretations of Variants in Cancer, OncoKB, Cancer Gene Census, Database of Curated Mutations, CGI Biomarkers (the cancer genome interpreter biomarker database), Tumor Alterations Relevant for Genomics-Driven Therapy, and the Precision Medicine Knowledge Base. METHODS: We downloaded each KB and restructured their content to describe variants, genes, drugs, and gene-drug associations in a common format. We normalized gene names to Entrez Gene IDs and drug names to ChEMBL and DrugBank IDs. For the analysis of clinically relevant gene-drug associations, we obtained lists of genes affected by genetic alterations and putative drug therapies for 113 patients with cancer whose cases were presented at the Molecular Tumor Board (MTB) of the Charité Comprehensive Cancer Center. RESULTS: Our analysis revealed that the KBs are largely overlapping but also that each source harbors a notable amount of unique information. Although some KBs cover more genes, others contain more data about gene-drug associations. Retrospective comparisons with findings of the Charitè MTB at the gene level showed...