HCDT 2.0: A Highly Confident Drug-Target Database for Experimentally Validated Genes, RNAs, and Pathways

Drug-target interactions constitute the fundamental basis for understanding drug action mechanisms and advancing therapeutic discovery. While existing drug-target databases have contributed valuable resources, they exhibit structural and functional fragmentation due to heterogeneous data sources and annotation standards. Building upon the high-confidence drug-gene interactions curated in HCDT 1.0, we present HCDT 2.0, a comprehensive and standardized resource that expands the scope through multiomics data integration. This update incorporates three-dimensional interactions including drug-gene, drug-RNA and drug-pathway interactions. The current version contains 1,284,353 curated interactions: 1,224,774 drug-gene pairs (678,564 drugs × 5,692 genes), 11,770 drug-RNA mappings (316 drugs × 6,430 RNAs), and 47,809 drug-pathway links (6,290 drugs ×3,143 pathways), alongside 16,317 drug-disease associations. To enhance biological interpretability, we further integrated pathway-gene and RNA-gene regulatory relationships. In addition, we integrated 38,653 negative DTIs covering 26,989 drugs and 1,575 genes. This integrative framework not only addresses critical gaps in cross-scale data representation but also establishes a robust foundation for systems pharmacology applications, including drug repurposing, adverse event prediction, and precision oncology strategies.

药物-靶点相互作用是解析药物作用机制、推动治疗性药物发现的核心基础。现有药物-靶点数据库虽已贡献诸多宝贵资源，但由于数据源异质性与注释标准不统一，仍存在结构与功能层面的碎片化问题。本研究基于HCDT 1.0中经人工整理的高置信度药物-基因相互作用数据集，推出HCDT 2.0——一款通过多组学数据整合实现范围拓展的全面标准化资源。本次更新纳入了包括药物-基因、药物-RNA以及药物-通路在内的三维相互作用数据。当前版本共包含1,284,353条经人工整理的相互作用数据：其中1,224,774条药物-基因配对（涉及678,564种药物与5,692个基因）、11,770条药物-RNA映射关系（涉及316种药物与6,430条RNA）、47,809条药物-通路关联（涉及6,290种药物与3,143条通路），此外还包含16,317条药物-疾病关联数据。为提升生物学可解释性，本研究进一步整合了通路-基因与RNA-基因调控关系数据。此外，本研究还整合了38,653条阴性药物-靶点相互作用（Drug-Target Interaction, DTI）数据，涉及26,989种药物与1,575个基因。该整合框架不仅填补了跨尺度数据表征领域的关键空白，同时也为系统药理学相关应用，包括药物重定位、不良事件预测以及精准肿瘤学策略开发，奠定了坚实基础。