Omics Core

组学核心

• 批准号: 10270579
• 负责人: Yunlong Liu
• 金额: $ 36.08万
• 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/10270579
• 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/antagonist; 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.

项目摘要/摘要 - OMICS核心 设计的发育和多动性RAS肿瘤（DHART）孢子旨在整合多个 研究项目的目的是确定与NF1相关的新分子理论策略 Malignancys。神经纤维瘤病1型（NF1）是一种常染色体显性疾病，其特征是突变 在编码神经纤维蛋白的NF1基因中。神经纤维蛋白的功能丧失，一种激活的Ras-GTPase 蛋白质（GAP）导致多活跃RAS信号传导和多个细胞信号通路的失调 影响细胞增殖和生存，例如Raf-Mek-ERK和PI3K-AKT-MTOR。总体目标 Omics Core（核心B）是为研究设计咨询提供最新的支持， 基因组学和激活实验，以及对DHART研究者的综合数据分析，以阐明 与NF1相关的肿瘤发展和对治疗的响应期间的变化。建立在制度基因组上 核心（医学基因组学中心），一个新成立的Kinome实验室和生物信息学研究 中心（计算生物学和生物信息学中心），核心B也与其他核心进行密切相互作用 支持Dhart的调查人员。收到追踪样品（包括小鼠和人类）后 神经纤维瘤，JMML，GBM和NF1相关的随后肿瘤的模型） 生物测量/病理核心C，将聘请以下技术和信息平台：1。核心 B将处理样品进行大量RNA测序，单细胞RNA测序，整个外显子组测序或 靶向外观测序。 2。轨道核心将分析和注释所有RNASEQ和外显子组测序 传输到突触的数据，用于数据分析的鼠尾草门户2。 化学蛋白质组学方法论可提供基于功能，基于活性的，全局的活性组合谱。 标本，定义基线活性状态，特定基因型或遗传扰动的影响以及反应 3。与行政核心A和Sage Bionetworks合作，集成 将进行分析以提供基因型驱动基因表达的综合分子谱。 和功能性活性谱。这些配置文件将用于推定的响应生物标志物和 候选治疗靶标。 Synapse，Sage维护的Web门户将允许孢子访问 OMICS和Biospecimen/病理核心获得的所有数据的研究者，发现将是 对孢子中参与的所有研究人员进行注释并更广泛地有用。此数据管理 门户网站将提供独特的资源，用于访问和解释由三个项目生成的数据， 生物测量和病理学核心和OMICS核心。