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.

在当前的精准医学时代，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检测， 核酸（DNAseq和/或RNAseq），其现在最典型地使用大规模平行测序来完成。 测序（MPS）。RNAseq现在提供了一种非常强大的查询肿瘤基因组的方法， 其中基因表达谱在提供预后信息，预测信息， 以及有关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的方法也可以在检测体细胞癌中提供临床信息。 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（扩增）。或者，测序测定可以靶向来自非癌细胞的DNA， 解决其他问题，包括确定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，USC-UTHSC UNITS团队将提供高容量的临床级测序， 从授予的第一天起就遵守法规。作为人类RNA生产的世界领先者- 基于冷冻和FFPE的癌症数据，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。我们也有丰富的经验， 复杂的、基于DNA的分析，并提供这些。本提案的目标1和2涉及提供FDA- 和CAP兼容机制，可实现高样本通量，用于样本的RNA和DNA测序 由多机构合作组试验提供。RNA测序将提供3种格式，RNA- Seq、NanoString和Q-rt-PCR，以实现全面覆盖和廉价的靶向RNA 侧写DNA测序将提供整个外显子组和MPS的靶向捕获，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， 用于正确传播基于临床试验序列的患者信息的基础设施， 这是一个大数据时代。