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.

到目前 疾病。人类组织（SMAHT）计划的躯体镶嵌化现在将扩大知识 正常组织中的这种关键基因组变异和对 在所有情况下体细胞变异的生物学。贝勒学院的基因组特征中心 医学人类基因组测序中心（HGSC）将表征750个组织样品的变化-1/3 该计划的15个个人中的15个样本中。新的步骤已纳入我们的研究 设计以全面发现体细胞突变。两种通用核心测定类型（WGS） 短阅读，长阅读和批量rnaseq）和两个其他分析（nanoseq和snrnaseq） 专业化将用于数据生成。基准标准，统一的数据结构和SOP 将使用既定的最新方法与其他网络成员合作创建 技术验证的发现和正交方法。满足性能的新技术 标准将引入生产。统计模型将指导组织取样和测序 策略，设定当前阈值，并进一步改进空间。 Nanoseq和单核RNA 将修改程序以提高性能并与调查人员进行密切合作 开发其他工具将确保最佳发现。本地分析将生成推定的列表 变体，特别关注长读序列数据的表征。后来将启用 在结构变化的证据中揭示了转置事件的建模以及变化 表观遗传标记的模式。所有数据将与DAC合作进行严格的QA/QC，并 在集中式数据存储库中镜像。