METEOR-BioLogical Specimen Translation (METEOR-BLST)

METEOR-生物样本翻译 (METEOR-BLST)

• 批准号: 10715024
• 负责人: Michael Benjamin Major
• 金额: $ 42.26万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715024
• 关键词: Adherence; Aftercare; Atlases; Bioinformatics; Biological; Biological Assay; Biological Response Modifier Therapy; Blood specimen; Cataloging; Cervix Neoplasms; Clinical; Collaborations; Comprehensive Cancer Center; Computer Analysis; Core Facility; Custom; Data; Data Analyses; Data Reporting; Development; Disease; Educational process of instructing; Ensure; Extramural Activities; Faculty; Feedback; Foundations; Funding; Human; Image; Institution; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Measures; Mentorship; Mission; Modeling; Molecular; Nuclear; Patients; Pre-Clinical Model; Procedures; Process; Proteins; Proteomics; Quality Control; Radiation therapy; Radiobiology; Reproducibility; Resource Sharing; Sampling; Scientist; Signal Pathway; Specimen; Statistical Data Interpretation; Technology; Testing; Time; Training; Translations; United States National Institutes of Health; Universities; Washington; cancer genomics; chemoradiation; data management; data quality; design; empowerment; exome sequencing; experience; innovation; insight; instrumentation; medical schools; metabolomics; mid-career faculty; multimodality; multiple omics; neoplastic cell; operation; pancreatic neoplasm; patient derived xenograft model; personalized medicine; protein function; radiomics; radioresistant; sample collection; standard of care; transcriptome sequencing; tumor; tumor microenvironment; tumor-immune system interactions

The BioLogical Specimen Translation (BLST) Shared Resource of the METEOR ROBIN Center was designed in concert with the leaders of both Projects, the METEORITE cross straining core and the CRATR Molecular Characterization Trial. The BLST shared resource provides expertise, instrumentation, and computational analyses for the full multimodal molecular characterization of cervical and pancreas tumor specimens before treatment, in-treatment and after treatment with radiation therapy. In doing so, the BLST will empower the projects and CRATR to test the global hypothesis that standard of care chemo-radiation therapy (CRT) remodels the tumor microenvironment to support the survival and expansion of radiation resistant tumor cells. We will provide instrumentation and proven experience for the following characterizations: 1) RNAseq and whole exome sequencing, 2) single nuclear snRNAseq and single nuclear snATACseq, 3) targeted SureQuant protein mass spectrometry, 4) NIMS-based spatial metabolomics and 5) spatial proteomics by CODEX. The BLST is not a stand-alone core facility, but rather functions integratively and synergistically across METEOR. Tumor and blood samples originate within the CRATR molecular characterization trial and from pre-clinical models within the Projects. The BLST will ensure sample quantity, quality, storage and tracking before analysis. Through a suite of pipelined commercial and custom computation, raw data produced in the BLST will be searched, statistically scored, integrated and bioinformatically analyzed. Raw and processed data will be transferred to the Data Management DST shared resource for further integration with clinical annotation and radiomics, as well as for storage and dissemination across the ROBIN consortium. Reciprocally, the DST shared resource will provide real-time feedback to the BLST for on-the-fly prioritization and pipeline adjustments. A direct line between the BLST and Projects enables real-time integration in guiding biological insight. Finally, the BLST will directly empower the Cross Training Core through associated faculty teaching and mentorship, as well as by providing various datatypes for trainee processing, integration and interpretation. To accomplish these objectives, we thematically organized the BLST across two Specific Aims. In Specific Aim #1, we will leverage optimized workflows to extract and comprehensively detect and quantify biomolecules from the METEOR CRATR clinical samples. As planned, the BLST will process: 15 samples for combined scRNAseq and scATACseq, 155 samples for scRNAseq, 70 samples for SureQuant targeted MS, 115 samples for NIMS metabomic imaging, and 85 for CODEX spatial proteomics. In Specific Aim #2, we will ensure adherence to principles of rigor and reproducibility and transparency. Data points will be integrated across platforms, space and time. Bioinformatic enrichment analyses will be used to annotate the resulting maps, including responding signaling pathways, protein functions, druggability, and disease associations. Finally, the BLST will collaborate across ROBIN centers to share its expertise and for continued optimization, data reporting and discovering of radiation biology.

设计了METEOR ROBIN中心的生物标本翻译（BLST）共享资源 与这两个项目的领导人，METEORITE交叉应变核心和CRATR分子 表征试验。BLST共享资源提供专业知识、仪器和计算能力。 分析之前宫颈和胰腺肿瘤标本的完整多模式分子特征 治疗、治疗中和放射治疗后。在这样做的时候，BLST将赋予 项目和CRATR，以检验护理标准化放疗（CRT）重塑 肿瘤微环境，以支持抗辐射肿瘤细胞的存活和扩增。我们将 为以下表征提供仪器和经验证的经验：1）RNAseq和全外显子组 测序，2）单核snRNAseq和单核snATACseq，3）靶向SureQuant蛋白质质量 光谱法，4）基于NIMS的空间代谢组学和5）CODEX的空间蛋白质组学。BLST不是一个 独立的核心设施，而是在整个METEOR中集成和协同运作。肿瘤和血液 样本来源于CRATR分子表征试验和临床前模型 项目分析前，BLST将确保样本数量、质量、储存和跟踪。通过一套 流水线的商业和定制计算，在BLST中产生的原始数据将被搜索，统计 评分、整合和生物信息学分析。原始数据和处理后的数据将传输至数据 管理DST共享资源，用于进一步与临床注释和放射组学集成， ROBIN联盟的存储和分发。反过来，DST共享资源将提供 实时反馈到BLST，以进行实时优先级排序和流水线调整。之间成直线 BLST和项目能够实时集成指导生物学洞察。最后，BLST将直接 通过相关的教师教学和指导，以及通过提供 用于学员处理、整合和解释的各种数据库。为了实现这些目标，我们 按照两个具体目标，对BLST进行了专题组织。在具体目标#1中，我们将利用优化的 从METEOR CRATR临床中提取、全面检测和定量生物分子的工作流程 样品按照计划，BLST将处理：15份scRNAseq和scATACseq组合样本，155份样本 对于scRNAseq，70个样本用于SureQuant靶向MS，115个样本用于NIMS代谢组学成像，85个样本用于 CODEX空间蛋白质组学在具体目标#2中，我们将确保遵守严格性和可重复性原则 和透明度。数据点将跨平台、跨空间和跨时间进行整合。生物信息富集 分析将用于注释所得到的图谱，包括响应信号通路，蛋白质功能， 药物性和疾病关联。最后，BLST将在ROBIN中心之间开展合作， 专业知识和持续优化，数据报告和发现辐射生物学。