Omics Core
Omics Core
批准号:
10494096
负责人:
Yunlong Liu
金额:
$37.56万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
未结题
起止时间:
2015-09-01 至 2026-08-31
关键词:
AddressBioinformaticsBiologicalBiologyCell ProliferationCell SurvivalCellsChemicalsCollaborationsComputational BiologyConsultationsCustomDataData AnalysesData SetDevelopmentDiseaseFRAP1 geneFundingGene ExpressionGeneticGenetically Engineered MouseGenomeGenomicsGenotypeGoalsGroup MeetingsHumanInformaticsKnowledgeLaboratoriesMEKsMalignant NeoplasmsMedical centerMethodologyMethodsModelingMolecularMolecular AnalysisMolecular ProfilingMorbidity - disease rateMusMutationMutation SpectraNF1 geneNeoplasmsNeurofibromatosis 1PathologyPathway AnalysisPathway interactionsPerformancePhosphotransferasesProcessProteomicsProto-Oncogene Proteins c-aktResearchResearch DesignResearch PersonnelResearch Project GrantsResearch SupportResourcesSamplingServicesSignal PathwaySignal TransductionSpecimenSynapsesSystemTechnologyTherapeuticbasedata and analysis portaldata exchangedata managementdesigneffective therapyexome sequencingexperimental studyfunctional losshyperactive Rasinformatics infrastructureinhibitorloss of functionmolecular targeted therapiesmortalitymultiple omicsneurofibromanext generation sequencingnovelnovel therapeuticspatient derived xenograft modelras GTPase-Activating Proteinsresponseresponse biomarkersingle-cell RNA sequencingtargeted exome sequencingtargeted treatmenttherapeutic candidatetherapeutic targettherapy resistanttranscriptometranscriptome sequencingtreatment responsetumortumor initiationtumor progressionweb portalworking group
中文摘要
项目总结/摘要-OMICS核心
发育和过度活跃Ras肿瘤(DHART)孢子旨在整合多种
研究项目,所有的目标是确定新的分子治疗策略NF 1相关的
恶性肿瘤1型神经纤维瘤病(NF1)是一种常染色体显性遗传疾病,其特征是基因突变
编码神经纤维蛋白的NF1基因。神经纤维蛋白(一种Ras-GT酶激活剂)的功能丧失
GAP蛋白导致Ras信号过度活跃和多种细胞信号通路失调
影响细胞增殖和存活,如Raf-MEK-ERK和PI3K-AKT-mTOR。的总体目标
组学核心(核心B)是为研究设计咨询提供最先进的支持,
基因组学和运动组学实验,以及DHART研究人员的综合数据分析,
NF 1相关肿瘤发展期间和对治疗反应的变化。基于机构基因组学
核心(医学基因组学中心),一个新成立的激酶组实验室,和一个生物信息学研究
核心B还与其他核心进行了密切的互动
支持DHART的调查员在收到跟踪样本(包括小鼠和人)后
神经纤维瘤、JMML、GBM和NF1相关的后续肿瘤模型)。
生物标本/病理学核心C,将采用以下技术和信息学平台:1.核心
B将处理用于批量RNA测序、单细胞RNA测序、全外显子组测序或
靶向外显子组测序。2.组学核心将分析和注释所有RNAseq和外显子组测序
将数据传输到Synapse,Sage数据分析门户2. Kinome Core将利用现有的
化学蛋白质组学方法,以提供NF 1相关的功能性、基于活性的全局激酶组谱
样本,定义基线激酶组状态,特定基因型或遗传扰动的影响,以及应答
靶向抑制剂。3.与行政核心A和Sage Bionetworks合作,
将进行分析,以提供基因型驱动的基因表达的全面分子概况
和功能性激酶组谱。将研究推定的反应生物标志物和
候选治疗靶点。由Sage维护的门户网站Synapse将允许SPORE访问
研究者对组学和生物标本/病理学核心获得的所有数据进行分析,
注释,并使其对参与SPORE的所有研究者更广泛地有用。本数据管理
门户网站将提供一个独特的资源,用于访问和解释这三个项目产生的数据,
生物标本和病理学核心和组学核心。
英文摘要
PROJECT SUMMARY/ABSTRACT – OMICS CORE
The Developmental and Hyperactive Ras Tumor (DHART) SPORE was designed to integrate multiple
research projects, all with the goal of identifying novel molecular therapeutic strategies for NF1-related
malignancies. Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, characterized by mutations
in the NF1 gene, which encodes neurofibromin. Functional loss of neurofibromin, a Ras-GTPase activating
protein (GAP) leads to hyperactive Ras signaling and dysregulation of multiple cell signaling pathways
impacting cell proliferation and survival, such as Raf-MEK-ERK and PI3K-AKT-mTOR. The overall goal of the
Omics Core (Core B) is to provide state-of-the-art support for research design consultation, performance of
genomics and kinomics experiments, and integrated data analysis to DHART investigators to elucidate
changes during NF1-related tumor development and in response to therapy. Built upon institutional genomics
cores (Center for Medical Genomics), a newly established kinome laboratory, and a bioinformatics research
center (Center for Computational Biology and Bioinformatics), Core B also interacts intensively with other cores
for supporting the DHART investigators. Upon receipt of tracked samples (including mouse and human
neurofibromas, JMML, GBM, and models of NF1-related subsequent neoplasms) from the
Biospecimen/Pathology Core C, the following technologies and informatics platforms will be employed: 1. Core
B will process samples for bulk RNA sequencing, single-cell RNA sequencing, whole exome sequencing, or
targeted exome sequencing. 2. The Omics Core will analyze and annotate all RNAseq and exome sequencing
data for transfer to Synapse, the Sage portal for data analysis 2. The Kinome Core will utilize established
chemical proteomics methodology to provide functional, activity-based, global kinome profiles of NF1-related
specimens, defining baseline kinome state, effects of specific genotype or genetic perturbations, and response
to targeted inhibitors. 3. In collaboration with the Administrative Core A and Sage Bionetworks, integrative
analyses will be performed to provide comprehensive molecular profiles of genotype-driven gene expression
and functional kinome profiles. The profiles will be studied for both putative response biomarkers and for
candidate therapeutic targets. Synapse, a web portal maintained by Sage will allow access by SPORE
investigators of all data obtained by the Omics and Biospecimen/Pathology Cores, where findings will be
annotated and made more broadly useful to all investigators involved in the SPORE. This data management
portal will provide a unique resource for accessing and interpreting data generated by the three projects,
Biospecimens and Pathology Core and Omics Core.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:10477070
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批准号:10247606
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批准号:9793157
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资助金额:$12.0万
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财政年份:--
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负责人:Yunlong Liu
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依托单位:
海外基金