CTDdgv: a comprehensive database for the identification and clinical interpretation of ctDNA driver genes and variants in cancer

Circulating tumor DNA (ctDNA) variants hold significant promise as cancer biomarkers in liquid biopsies, owing to their minimally invasive testing approach and capacity to capture the comprehensive tumor landscape. However, a comprehensive resource for studying ctDNA variants is still lacking. Here, we developed CTDdgv, which aims to identify ctDNA variants and interpret their clinical relevance systematically. We manually curated 1674 experimentally validated clinical interpretations for ctDNA variants, concerning prognostic significance, drug resistance, associations with tumor characteristics, metastasis monitoring, therapy guiding, prospect for detection, and others. Furthermore, we developed and integrated a pipeline that identifies tumor driver genes (TDGs) and variants (TDVs) and evaluates the prognostic significance of potential TDGs. Using publicly available ctDNA mutation spectra, we identified potential TDGs and TDVs from 38 datasets across 17 cancer types. Based on these data sets, we provide the multi-dimensional analysis of TDG gene sets in specific cancer types, providing insights into their driving effects. Collectively, CTDdgv has significant potential to serve as a valuable resource for molecular diagnostics and therapeutic decision-making in cancer via liquid biopsy.