Qu Shoufang, Liu Rongzhi, Li Shisen, Huang Chuanfeng, Zhang Yingqian, Gao Xuan, Dai Pingping, Xu Chao, Yang Rutao, Li Xuchao, Ouyang Guojun, Shao Kang, Chang Xiaoyan, Mu Feng, Yang Meng, Huang Jie
Department of in Vitro Diagnostic Reagent, National Institutes for Food and Drug Control (NIFDC), No.2 Tiantanxili, Dongcheng District, Beijing, 10050, China.
Center for Medical Device Evaluation (CMDE), National Medical Products Administration (NMPA), No.50, Qixiang Road, Haidian District, Beijing, 100081, China.
Hum Genet. 2025 Aug 31. doi: 10.1007/s00439-025-02764-8.
High-quality, regulatory-grade databases for precise genetic variant interpretation are critically needed for Chinese populations, where existing fragmented databases impede clinical effectiveness evaluations. We developed BRCA-CN, a consortium blockchain-based governance framework specifically designed for BRCA gene variant interpretation in Chinese populations. Our framework compiled 66,485 variants from 6,031 samples across six Chinese laboratories. A 15-expert panel conducted systematic variant curation using unified interpretation standards based on ACMG/AMP guidelines. Smart contracts ensured data integrity and accountability throughout the consensus process. After deduplication, we established a comprehensive database of 950 unique variants (BRCA1: 365, BRCA2: 585), completing consensus reviews for 607 sites with 462 achieving definitive interpretations. Comparison with ClinVar revealed 83.6% concordance, with AI validation (PrimateAI, REVEL, EVE) confirming high interpretation accuracy. The blockchain framework successfully enabled secure cross-institutional collaboration while maintaining data sovereignty and regulatory compliance. BRCA-CN demonstrates the transformative potential of blockchain technology in genomic medicine, addressing critical challenges in data sharing, standardization, and regulatory oversight. This framework provides a robust foundation for clinical decision-making and establishes a replicable model for population-specific genomic databases. Access to the BRCA-CN portal, user guides, and test data is provided in the supplementary materials, available at: https://oxygen-chamber.mgi-tech.com/sdb2.
中国人群迫切需要高质量、符合监管要求的数据库来进行精确的基因变异解读,因为现有的碎片化数据库阻碍了临床疗效评估。我们开发了BRCA-CN,这是一个基于联盟区块链的治理框架,专门为中国人群的BRCA基因变异解读而设计。我们的框架整合了来自中国六个实验室的6031个样本中的66485个变异。一个由15名专家组成的小组根据ACMG/AMP指南使用统一的解读标准进行了系统的变异整理。智能合约在整个共识过程中确保了数据的完整性和可追溯性。经过去重后,我们建立了一个包含950个独特变异的综合数据库(BRCA1:365个,BRCA2:585个),完成了对607个位点的共识审查,其中462个位点获得了明确的解读。与ClinVar的比较显示一致性为83.6%,人工智能验证(PrimateAI、REVEL、EVE)证实了解读的高准确性。区块链框架成功地实现了安全的跨机构合作,同时保持了数据主权和监管合规。BRCA-CN展示了区块链技术在基因组医学中的变革潜力,解决了数据共享、标准化和监管监督方面的关键挑战。该框架为临床决策提供了坚实的基础,并建立了一个针对特定人群的基因组数据库的可复制模型。补充材料中提供了对BRCA-CN门户、用户指南和测试数据的访问,网址为:https://oxygen-chamber.mgi-tech.com/sdb2 。