METEOR-BioLogical Specimen Translation (METEOR-BLST)
METEOR-BioLogical Specimen Translation (METEOR-BLST)
批准号:
10715024
负责人:
Michael Benjamin Major
金额:
$42.26万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-01 至 2028-08-31
关键词:
AdherenceAftercareAtlasesBioinformaticsBiologicalBiological AssayBiological Response Modifier TherapyBlood specimenCatalogingCervix NeoplasmsClinicalCollaborationsComprehensive Cancer CenterComputer AnalysisCore FacilityCustomDataData AnalysesData ReportingDevelopmentDiseaseEducational process of instructingEnsureExtramural ActivitiesFacultyFeedbackFoundationsFundingHumanImageInstitutionMalignant NeoplasmsMapsMass Spectrum AnalysisMeasuresMentorshipMissionModelingMolecularNuclearPatientsPre-Clinical ModelProceduresProcessProteinsProteomicsQuality ControlRadiation therapyRadiobiologyReproducibilityResource SharingSamplingScientistSignal PathwaySpecimenStatistical Data InterpretationTechnologyTestingTimeTrainingTranslationsUnited States National Institutes of HealthUniversitiesWashingtoncancer genomicschemoradiationdata managementdata qualitydesignempowermentexome sequencingexperienceinnovationinsightinstrumentationmedical schoolsmetabolomicsmid-career facultymultimodalitymultiple omicsneoplastic celloperationpancreatic neoplasmpatient derived xenograft modelpersonalized medicineprotein functionradiomicsradioresistantsample collectionstandard of caretranscriptome sequencingtumortumor microenvironmenttumor-immune system interactions
中文摘要
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
样品按计划,BLST将处理:组合scRNAseq和scATACseq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。
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:10064849
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负责人:Michael Benjamin Major
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批准号:10117197
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资助金额:$50.37万
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Role of FOXP1 and WNT signaling in B-cell Lymphoma
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批准号:10025735
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资助金额:$29.83万
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财政年份:2015
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依托单位:
Role of FOXP1 and WNT signaling in B-cell Lymphoma
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批准号:9304063
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资助金额:$30.75万
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财政年份:2015
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Mass spectrometry-coupled hypermorphic functional genomics
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批准号:8917142
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资助金额:$16.44万
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依托单位:
Mass spectrometry-coupled hypermorphic functional genomics
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批准号:8692117
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资助金额:$19.74万
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负责人:Michael Benjamin Major
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依托单位:
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批准号:9044453
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资助金额:$2.05万
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财政年份:2010
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负责人:Michael Benjamin Major
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依托单位:
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批准号:10247138
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资助金额:$4.67万
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Exploitation of Near-Haploid Human Cells for Functional Gene Discovery
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批准号:7981207
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资助金额:$222.0万
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财政年份:--
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