METEOR-BioLogical Specimen Translation (METEOR-BLST)

设计了流星知更鸟中心生物标本翻译(BLST)共享资源 在这两个项目的领导下，陨石交叉应变核心和CRATR分子 定性试验。BLST共享资源提供专业知识、工具和计算 宫颈和胰腺肿瘤标本的全多峰分子特征分析 治疗、治疗中和治疗后均采用放射治疗。通过这样做，BLST将赋予 项目和CRATR以检验全球假说，即标准护理放化疗(CRT)重塑 肿瘤微环境支持抗辐射肿瘤细胞的生存和扩张。我们会 为以下特征提供工具和成熟的经验：1)RNAseq和整个外显子组 测序，2)单核SnRNAseq和单核SnATACseq，3)靶向SureQuant蛋白质量 基于NIMS的空间代谢组学和5)Codex的空间蛋白质组学。BLST不是 独立的核心设施，而是跨流星的综合和协同功能。肿瘤与血液 样本来自CRATR分子特征试验和临床前模型 项目。BLST将在分析前确保样品的数量、质量、存储和跟踪。通过套间 在流水线商业和定制计算中，将从统计上搜索在BLST中产生的原始数据 评分、综合和生物信息分析。原始数据和处理后的数据将被传输到数据 管理DST共享资源，以进一步集成临床注释和放射组学，以及 在罗宾财团之间的存储和传播。反过来，DST共享资源将提供 向BLST提供实时反馈，以便即时确定优先顺序和调整管道。两者之间的直接联系 BLST和项目实现了在指导生物学洞察方面的实时集成。最后，BLST将直接 通过联合教员授课和指导，以及通过提供 用于学员处理、集成和解释的各种数据类型。为了达到这些目标，我们 在两个具体目标上有主题地组织了BLST。在具体目标1中，我们将利用优化 从流星CRATR临床中提取、全面检测和量化生物分子的工作流 样本。按计划，BLST将处理：scRNAseq和scATACseq组合的15个样本，155个样本 对于scRNAseq，70个样本用于SureQuant靶向MS，115个样本用于NIMS代谢组成像，85个样本用于 食典空间蛋白质组学。在具体目标2中，我们将确保遵守严谨和可重复的原则 和透明度。数据点将跨平台、跨空间、跨时间整合。生物信息学浓缩 分析将被用于注释结果图，包括响应信号通路，蛋白质功能， 可药性，和疾病的联系。最后，BLST将在罗宾中心之间协作，共享其 该中心将继续提供辐射生物学方面的专门知识和持续优化、数据报告和发现服务。

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.