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.

循环肿瘤DNA（ctDNA）变异体作为液体活检中的癌症生物标志物具有重要前景，这得益于其微创检测方式及捕捉全面肿瘤图谱的能力。然而，目前仍缺乏用于研究ctDNA变异体的综合性资源。为此，我们开发了CTDdgv数据库，旨在系统识别ctDNA变异体并阐释其临床相关性。我们手动整理了1674条经实验验证的ctDNA变异体临床解读，涵盖预后意义、耐药性、与肿瘤特征的关联、转移监测、治疗指导、检测前景等方面。此外，我们开发并整合了一套分析流程，用于识别肿瘤驱动基因（TDGs）和变异体（TDVs），并评估潜在TDGs的预后意义。利用公开可用的ctDNA突变谱，我们从17种癌症类型的38个数据集中识别出潜在的TDGs和TDVs。基于这些数据集，我们提供了特定癌症类型中TDG基因集的多维分析，以深入了解其驱动效应。总体而言，CTDdgv有望作为液体活检在癌症分子诊断和治疗决策中的宝贵资源。