Comprehensive Somatic Variant Characterization at the HGSC

HGSC 的综合体细胞变异表征

• 批准号: 10662645
• 负责人: RUI CHEN
• 金额: $ 250万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662645
• 关键词: Aging; Benchmarking; Biological Assay; Biology; Calibration; Catalogs; Collaborations; Common Core; Communication; Data; Data Analyses; Detection; Development; Developmental Process; Disease; Ecosystem; Elements; Ensure; Epigenetic Process; Evaluation; Event; Future; Generations; Genetic; Genome; Health; Human; Individual; Knowledge; Laboratories; Life; Link; Malignant Neoplasms; Medicine; Methods; Modeling; Monitor; Mosaicism; Mutagenesis; Mutation; Nitrites; Normal tissue morphology; Nuclear RNA; Pathogenicity; Pattern; Performance; Phase; Predisposition; Procedures; Process; Production; Protocols documentation; Research Design; Research Personnel; Role; Sampling; Software Tools; Somatic Mutation; Standardization; Statistical Models; Structure; Technology; Testing; Tissue Sample; Tissues; Validation; Variant; Work; college; data exchange; data format; data harmonization; data repository; design; genome sequencing; genomic variation; human disease; human genome sequencing; human tissue; improved; insight; member; new technology; novel; programs; sequencing platform; software development; success; tool; transcriptome sequencing; variant detection; web interface; whole genome

Studies of somatic mutations have so far focused on pathogenic variation, leading to cancer or severe disease. The Somatic Mosaicism Across Human Tissues (SMaHT) program will now expand knowledge of this critical class of genomic variation in normal tissues and build a comprehensive understanding of the biology of somatic variation in all contexts. The Genome Characterization Center at the Baylor College of Medicine Human Genome Sequencing Center (HGSC) will characterize variation in 750 tissue samples - 1/3 of the Program’s 15 samples from each of 150 individuals. Novel steps have been incorporated into our study design to enable comprehensive discovery of somatic mutations. Both common core assay types (WGS short-read, long read and bulk RNAseq) and two additional assays (nanoSeq and snRNAseq) that our group specializes will be used for data generation. Benchmark standards, harmonized data structures and SOPs will be created in collaboration with other Network members using established state-of-the-art methods for discovery and orthogonal approaches for technical validation. New technologies that satisfy performance criteria will be introduced into production. Statistical models will guide tissue-subsampling and sequencing strategies, set the current thresholds with further room for improvement. NanoSeq and single nuclear RNA procedures will each be modified for enhanced performance and close collaboration with investigators developing additional tools will ensure optimal discovery. Local analyses will generate lists of putative variants, with a particular focus upon characterization of long read sequence data. The latter will enable modelling of transposition events, revealed within evidence for structural variation, as well as changes in patterns of epigenetic marks. All data will be subjected to rigorous QA/QC, in collaboration with the DAC, and mirrored in the centralized data repository.

迄今为止，体细胞突变的研究主要集中在导致癌症或严重疾病的致病变异上。 人体组织中的体细胞镶嵌（SMaHT）计划现在将扩展对疾病的认识。 正常组织中这一类关键的基因组变异，并建立对 贝勒学院基因组表征中心的体细胞变异生物学。 医学人类基因组测序中心 (HGSC) 将表征 750 个组织样本的变异 - 1/3 该计划的 15 个样本均来自 150 个人，新颖的步骤已纳入我们的研究中。 设计以实现体细胞突变的全面发现两种常见的检测核心类型（WGS）。 短读长、长读长和批量 RNAseq）以及我们小组的另外两种检测（nanoSeq 和 snRNAseq） 专家将用于数据生成、统一数据结构和SOP。 将使用既定的最先进方法与其他网络成员合作创建 满足性能的新技术的发现和正交方法。 标准将被引入生产中。统计模型将指导组织二次采样和测序。 策略，设定当前的阈值，并具有进一步改进的空间。 每个程序都将进行修改，以提高性能并与调查人员密切合作 开发额外的工具将确保最佳的发现。本地分析将生成假定的列表。 变体，特别关注长读序列数据的表征。 转座事件的建模，在结构变异的证据中揭示，以及变化 表观遗传标记的模式将与 DAC 合作接受严格的 QA/QC，以及 镜像在集中式数据存储库中。