Omics Core

组学核心

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要 – 组学核心发育性和过度活跃的 Ras 肿瘤 (DHART) SPORE 旨在整合多个研究项目，所有目标都是确定 NF1 相关的新型分子治疗策略 1 型神经纤维瘤病 (NF1) 是一种常染色体显性遗传疾病，其特征为突变。 NF1 基因编码神经纤维蛋白，一种 Ras-GTP 酶激活剂，功能丧失。蛋白 (GAP) 导致 Ras 信号传导过度活跃和多个细胞信号传导途径失调影响细胞增殖和存活，例如 Raf-MEK-ERK 和 PI3K-AKT-mTOR 的总体目标。 Omics Core（核心 B）旨在为研究设计咨询、执行基因组学和运动学实验，以及整合数据分析以供 DHART 研究人员阐明 NF1相关肿瘤发展过程中的变化以及对治疗的反应建立在机构基因组学的基础上。 cores（医学基因组学中心）、新成立的激酶组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也与其他核心密切互动用于支持 DHART 研究人员收到跟踪样本（包括小鼠和人类）。神经纤维瘤、JMML、GBM 和 NF1 相关后续肿瘤模型）生物样本/病理学核心C，将采用以下技术和信息学平台： 1. 核心 B 将处理样品进行批量 RNA 测序、单细胞 RNA 测序、全外显子组测序，或 2. Omics Core 将分析和注释所有 RNAseq 和外显子组测序。数据传输到 Synapse（用于数据分析的 Sage 门户） 2. Kinome Core 将利用已建立的化学蛋白质组学方法提供 NF1 相关功能性、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反应 3. 与行政核心 A 和 Sage Bionetworks 合作，整合。将进行分析以提供基因型驱动的基因表达的全面分子谱和功能激酶组谱将研究假定的反应生物标志物和功能激酶组谱。由 Sage 维护的门户网站 Synapse 将允许 SPORE 访问。研究人员对组学和生物样本/病理学核心获得的所有数据进行研究，结果将对参与 SPORE 数据管理的所有研究人员进行了注释并使其更广泛地有用。门户网站将提供独特的资源来访问和解释这三个项目生成的数据，生物样本和病理学核心和组学核心。