Clinical Research-Oriented Gene Sequencing Projects: Rationale, Management and Quality Control Standards

doi:10.3969/j.issn.1673-5765.2022.03.003

Abstract

Abstract: Objective To develop the standards for clinical research-oriented gene sequencing project management and data quality control pipeline, and provide technical support for cohort-based omics analysis, disease mechanism exploration, and drug target development. Methods Based on the gene sequencing protocol of small samples in biomedical research and with reference to international large-scale sequencing cohorts, a clinical research-oriented gene sequencing project framework was constructed. The management process was designed and optimized in terms of multiple procedures, such as sample processing, sequencing data generation, bioinformatics analysis, project quality assurance, data safety and biobank safety. Results The rationale of clinical research oriented-gene sequencing projects was determined, and the management pipeline was established. By applying this pipeline to the China national stroke registry-Ⅲ (CNSR-Ⅲ) cohort, data quality control standards were established, including DNA extraction and library preparation standards, sequencing and genetic variants identification standards, sample clinical information inference standards, mutual verification of genetic testing data standards, etc. Conclusions The application of genetic testing in clinical research, with its standardized

management pipeline, data analysis, and unified quality control standards, could meet the scalability,

traceability and reproducibility requirements of scientific research. The gene sequencing project management and data quality control standards established in this study has been successfully verified in the CNSR-Ⅲ cohorts, and can be used as a reference standard for gene sequencing projects in other clinical studies.

Key words: Genetic testing; Whole genome sequencing; Clinical research; Quality control

摘要：

目的开发并搭建适用于临床研究的基因测序项目管理和数据质量控制流程，为基于队列的组学分析、疾病机制探索、药物靶标开发等提供技术保障。

方法基于生物医学研究中小样本的测序流程，参考国际大规模测序队列，形成面向临床研究的基因测序项目框架。从样本处理、测序数据生成、生物信息学分析、项目的质量保证、数据安全与生物样本安全等多个环节，进行管理流程的搭建和优化。

结果确定了面向临床研究的基因测序项目的设计原则，搭建了系统性管理流程。通过将此流程应用于中国国家卒中登记Ⅲ（China national stroke registry-Ⅲ，CNSR-Ⅲ）队列，建立了数据质控标准，包括DNA提取和文库制备质控、测序和遗传变异鉴定质控、样本临床信息推断质控和基因检测数据的相互验证等。

结论在临床研究中将基因检测纳入试验设计，并采用标准化的管理流程、数据分析方案和统一的质控标准，能够满足科学研究的可扩展性、可重复性、可溯源性的需求。本研究搭建的基因测序项目管理流程和质控标准已在CNSR-Ⅲ队列上验证成功，可以作为其他临床研究中此类项目的参考标准。

关键词: 基因检测; 全基因组测序; 临床研究; 质量管理

LIU Yang, XU Zhe, CHENG Si, SHI Yanfeng, LIN Jinxi, MENG Xia, JIANG Yong, LI Hao. Clinical Research-Oriented Gene Sequencing Projects: Rationale, Management and Quality Control Standards[J]. Chinese Journal of Stroke, 2022, 17(03): 227-235.

刘阳, 许喆, 程丝, 石延枫, 林金嬉, 孟霞, 姜勇, 李昊. 面向临床研究的基因测序项目的设计原则、管理流程与质量控制标准[J]. 中国卒中杂志, 2022, 17(03): 227-235.

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