Omics Core

组学核心

• 批准号: 10494096
• 负责人: Yunlong Liu
• 金额: $ 37.56万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10494096
• 关键词: Address; Bioinformatics; Biological; Biology; Cell Proliferation; Cell Survival; Cells; Chemicals; Collaborations; Computational Biology; Consultations; Custom; Data; Data Analyses; Data Set; Development; Disease; FRAP1 gene; Funding; Gene Expression; Genetic; Genetically Engineered Mouse; Genome; Genomics; Genotype; Goals; Group Meetings; Human; Informatics; Knowledge; Laboratories; MEKs; Malignant Neoplasms; Medical center; Methodology; Methods; Modeling; Molecular; Molecular Analysis; Molecular Profiling; Morbidity - disease rate; Mus; Mutation; Mutation Spectra; NF1 gene; Neoplasms; Neurofibromatosis 1; Pathology; Pathway Analysis; Pathway interactions; Performance; Phosphotransferases; Process; Proteomics; Proto-Oncogene Proteins c-akt; Research; Research Design; Research Personnel; Research Project Grants; Research Support; Resources; Sampling; Services; Signal Pathway; Signal Transduction; Specimen; Synapses; System; Technology; Therapeutic; base; data and analysis portal; data exchange; data management; design; effective therapy; exome sequencing; experimental study; functional loss; hyperactive Ras; informatics infrastructure; inhibitor; loss of function; molecular targeted therapies; mortality; multiple omics; neurofibroma; next generation sequencing; novel; novel therapeutics; patient derived xenograft model; ras GTPase-Activating Proteins; response; response biomarker; single-cell RNA sequencing; targeted exome sequencing; targeted treatment; therapeutic candidate; therapeutic target; therapy resistant; transcriptome; transcriptome sequencing; treatment response; tumor; tumor initiation; tumor progression; web portal; working group

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.

项目概要/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（NF 1）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NF 1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PI 3 K-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， 在NF 1相关肿瘤发展过程中以及对治疗的反应中的变化。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NF 1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 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。