UNITS: The UNC / UT National Clinical Trials Network Group Integrated Translational Science Production and Consultation Center

单位：北卡罗来纳大学/德克萨斯大学国家临床试验网络集团综合转化科学生产和咨询中心

• 批准号: 10581560
• 负责人: David N Hayes
• 金额: $ 72.84万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-13 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10581560
• 关键词: Acceleration; Accreditation; Address; Adjuvant Study; Adoption; B-Cell Antigen Receptor; Base Sequence; Big Data; Biological Assay; Biological Markers; CLIA certified; Cancer Patient; Cells; Center for Translational Science Activities; Clinic; Clinical; Clinical Data; Clinical Trials; Clinical Trials Cooperative Group; Clonality; Complex; Consultations; DNA; DNA Sequence; DNA Sequence Alteration; DNA copy number; DNA sequencing; Data; Data Analyses; Data Mart; Diagnosis; Disease; Expression Profiling; Formalin; Freezing; Funding; Gene Expression; Gene Expression Profiling; Genomic medicine; Genomics; Genotype; Goals; Grant; Head; Hereditary Malignant Neoplasm; Human; Immune; Immune system; Immunotherapy; Infrastructure; Institution; Laboratories; Laboratory Study; Location; Malignant Neoplasms; Massive Parallel Sequencing; Measures; Methods; Molecular Target; Mutation; Mutation Detection; National Clinical Trials Network; Neoadjuvant Therapy; Nucleic Acids; Paraffin Embedding; Patients; Pharmaceutical Preparations; Pharmacogenomics; Ploidies; Precision Medicine Initiative; Predisposition; Privacy; Process; Production; RNA; Reproducibility; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Sampling; Science; Selection for Treatments; Specimen; Speed; Staging System; Standardization; Syndrome; T-Lymphocyte; Technical Expertise; Techniques; Technology; The Cancer Genome Atlas; Time; Translational Research; United States National Institutes of Health; Variant; analysis pipeline; biomarker development; cancer clinical trial; cancer genome; clinical decision-making; clinically relevant; cost efficient; data access; data dissemination; data sharing; data submission; database of Genotypes and Phenotypes; exome; experience; genome-wide; genomic data; human subject; human subject protection; immune cell infiltrate; improved; mRNA sequencing; malignant breast neoplasm; nano-string; neoantigens; next generation; next generation sequencing; novel; open data; personalized medicine; precision medicine; privacy protection; prognostic; receptor; single-cell RNA sequencing; therapeutic enzyme; transcriptome; transcriptome sequencing; tumor; tumor microenvironment; whole genome

In the current era of Precision Medicine, laboratory studies are an integral component of cancer clinical trials. Amongst the most powerful techniques connecting therapies to specific patients are assays that interrogate nucleic acids (DNAseq and/or RNAseq), which are now most typically done using massively parallel sequencing (MPS). RNAseq now offers an extremely powerful approach for querying the tumor genome, where gene expression profiles have proven value in providing prognostic information, predictive information, and also critical information on the tumor microenvironment including quantitative measures of immune infiltrations. In addition, DNA based approaches can also be clinically informative in detecting somatic sequence alterations (mutations), structural variations (fusions), loss of normal DNA sequences (deletions), or sequence gains (amplifications). Alternatively, sequencing assays can target DNA from noncancerous cells to address additional questions including identification of familial predisposition, and genotyping of drug metabolizing enzymes of therapeutic importance. Through this Project, the UNC / UTHSC UNITS team will provide high volume clinical grade sequencing in a regulatory compliant manner from day one of the grant. As a world leader in the production of human RNA- based cancer data, from both frozen and FFPE, including RNA sequencing and targeted RNA quantification, RNA-based assays are offered within a compliant setting. We are also highly experienced with common, and complex, DNA-based assays and offer these as well. Aims 1 and 2 of this proposal involve providing an FDA- and CAP- compliant mechanism for high sample throughput for RNA- and DNA-sequencing from samples provided from multi-institutional cooperative group trials. RNA sequencing will be offered in 3 formats, RNA- Seq, NanoString, and Q-rt-PCR, to allow both comprehensive coverage and inexpensive targeted RNA profiling. DNA sequencing will be offered for both whole exome and targeted capture by MPS, as well as quantitative DNA measures by NanoString. The third aim is to develop and provide data sharing formats and an infrastructure for the proper dissemination of clinical trial sequence-based patient information, which is needed is this era of Big Data.

在当今精准医学时代，实验室研究是癌症临床试验不可或缺的组成部分。 将治疗与特定患者联系起来的最强大的技术之一是询问的检测 核酸（DNAseq 和/或 RNAseq），现在通常使用大规模并行技术来完成 测序（MPS）。 RNAseq 现在提供了一种极其强大的方法来查询肿瘤基因组， 基因表达谱已被证明在提供预后信息、预测信息、 以及肿瘤微环境的关键信息，包括免疫的定量测量 渗透。此外，基于 DNA 的方法还可以为检测体细胞提供临床信息。 序列改变（突变）、结构变异（融合）、正常 DNA 序列丢失（缺失），或 序列增益（放大）。或者，测序分析可以将非癌细胞的 DNA 靶向 解决其他问题，包括识别家族易感性和药物基因分型 具有治疗重要性的代谢酶。 通过该项目，北卡罗来纳大学/UTHSC UNITS 团队将在 从拨款的第一天起就遵循监管合规的方式。作为人类 RNA 生产领域的世界领先者 来自冷冻和 FFPE 的基于癌症数据，包括 RNA 测序和靶向 RNA 定量， 基于 RNA 的检测在合规环境中提供。我们在常见问题和 复杂的、基于 DNA 的检测并提供这些检测。该提案的目标 1 和 2 涉及提供 FDA- 和 CAP 兼容机制，可实现样品 RNA 和 DNA 测序的高样品通量 由多机构合作小组试验提供。 RNA测序将以3种形式提供，RNA- Seq、NanoString 和 Q-rt-PCR，可实现全面覆盖和廉价的靶向 RNA 分析。 MPS 将为全外显子组和靶向捕获提供 DNA 测序，以及 通过 NanoString 进行定量 DNA 测量。第三个目标是开发和提供数据共享格式和 用于正确传播基于临床试验序列的患者信息的基础设施，该信息是 这个时代需要的是大数据。