Omics Core

项目摘要/摘要-OMICS核心 发育和高度活跃的RAS肿瘤(DHART)孢子被设计成整合多个 研究项目，所有项目的目标都是确定NF1相关的新分子治疗策略 恶性肿瘤。1型神经纤维瘤病(NF1)是一种常染色体显性遗传病，以突变为特征 在NF1基因中，它编码神经纤维素。激活Ras-GTP酶的神经纤维蛋白功能丧失 蛋白质(GAP)导致RAS信号过度活跃和多个细胞信号通路的失调 影响细胞增殖和存活的基因，如Raf-MEK-ERK和PI3K-AKT-mTOR。该计划的总体目标 组学核心(核心B)是为研究设计咨询提供最先进的支持，性能 基因组学和运动学实验，以及集成的数据分析，以帮助DHART调查人员阐明 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基础上 CORES(医学基因组学中心)，一个新成立的基因组实验室和一个生物信息学研究 中心(计算生物学和生物信息学中心)，核心B也与其他核心密切交互 支持DHART的调查人员。在收到跟踪样本时(包括老鼠和人 神经纤维瘤、JMML、GBM和NF1相关后续肿瘤的模型)来自 将采用以下技术和信息学平台：1.核心 B将对样本进行批量RNA测序、单细胞RNA测序、整个外显子组测序或 靶向外显子组测序。2.Omics Core将分析和注释所有RNAseq和外显子组序列 将数据传输到用于数据分析的Sage门户网站Synapse 2.Kinome Core将利用已建立的 提供NF1相关功能、基于活性的全球基因组图谱的化学蛋白质组学方法学 样本，定义基线染色体状态，特定基因或遗传扰动的影响，以及反应 到靶向抑制剂。3.与行政核心A和圣贤生物网络合作，综合 将进行分析，以提供由基因型驱动的基因表达的全面分子图谱 和功能上的染色体组特征。将对推测的反应生物标志物和 候选治疗靶点。Sage维护的门户网站Synapse将允许孢子访问 OMICS和Biospecimen/病理核心获得的所有数据的调查人员，调查结果将在那里 并使其更广泛地适用于参与该孢子的所有调查人员。此数据管理 门户网站将为访问和解释这三个项目产生的数据提供独特的资源， 生物化学与病理学核心和全基因组学核心。

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.