Core 2: Applied Meta'Omics Core

核心 2：应用元组学核心

• 批准号: 10259875
• 负责人: Mark James Cameron
• 金额: $ 33.14万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259875
• 关键词: Address; Animal Model; Artificial Intelligence; Big Data; Bioinformatics; Biological Assay; Biological Markers; Cell model; Clinical; Data; Data Analyses; Data Set; Databases; Development; Diagnostic; Disease; Drug Targeting; Evaluation; Event; FDA approved; Future; Gene Expression; Gene Expression Profile; Gene Targeting; Generations; Genes; Genetic; Genetic Transcription; Genomics; Goals; Grant; Human; Immune response; Immunologics; Individual; Inflammation; Inflammatory; Inflammatory Response; Lead; Literature; Machine Learning; Mediating; Methodology; Modernization; Multiomic Data; Mus; Mutation; Outcome; Pathogenesis; Pathologic; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Pre-Clinical Model; Preparation; Psoriasis; RNA analysis; Reporting; Research Project Grants; Resolution; Resources; Sampling; Services; Skin; Systems Biology; Techniques; Technology; Testing; Therapeutic; Translating; Translational Research; Validation; bioinformatics pipeline; candidate marker; clinical application; clinical care; cohort; comorbidity; data mining; data modeling; deep sequencing; design; differential expression; drug candidate; efficacy testing; experimental study; high throughput technology; human model; indexing; individualized medicine; innovation; insight; metabolomics; microbiome; mouse model; mycobiome; new therapeutic target; novel; potential biomarker; targeted biomarker; targeted treatment; transcriptome sequencing; transcriptomics

To date, most existing cellular or immunological evaluations of psoriasis inflammation have been limited by the low-resolution data used for analysis and often rely on gross clinical endpoints. The overall goal of the CORT is to combine new bioinformatic methodologies with advanced murine and human experimental approaches to translate scientific findings into clinical applications that more nimbly advance therapy for psoriasis and related inflammatory comorbidities. Systems biology provides an unbiased approach to generating a comprehensive assessment of the host responses involved in psoriasis-mediated inflammation that may lead to new therapy targets for psoriasis and ideally, those tailored for the specific patient. This evolving investigative paradigm driven by modern high-throughput technologies that generate enormous datasets (“Big Data”) has engendered the need for a centralized ‘omics core service and analysis platforms that the CORT Applied Meta’Omics Core (AMC) will provide. The AMC is designed to serve as an innovative collaborative resource with bidirectional experimental ties to the Collaborative Research Project (CRP) and Preclinical Modeling Core (PMC). The AMC will receive samples from the CRP and PMC, generate transcriptomic, metabolomic, microbiome and mycobiome datasets, and provide the bioinformatic pipelines to analyze those datasets in conjunction with clinical outcomes and/or other data types, including incorporation of artificial intelligence, data mining, network techniques and machine learning to enable identification of novel pathways and differentially-expressed gene targets that will allow for identification of new and/or re-purposed drugs. The AMC supports the CORT CRP’s overall objectives via the following aims: (1) perform SOP-driven sample acquisition, sample preparation, and ‘omic assays for the PMC and CRP; (2) identify differential metabolomic, gene and pathway expression signatures, as well as changes in the micro/mycobiome, between psoriatic involved, uninvolved and control skin from human and psoriasiform murine models for the CRP; (3) (i) identify systems biology donor profiles (endotypes) and candidate biomarkers that may define the pathogenesis of psoriasis in humans and mouse models and (ii) identify FDA-approved drugs that are predicted to target the biomarkers and/or pathways associated with psoriasis. Highly interactive Cores synergistically interacting with the central CRP, the AMC team's expertise, innovation and extensive resources will drive the CORT's transforming and sustainable impact on psoriasis understanding and clinical care. The AMC will shed deeper insight into the pathological events in psoriasis, which can be translated into targeted diagnostic and therapeutic strategies to manage psoriasis at the individual level. By combining myco/microbiome, metabolomic, and transcriptomic analyses to identify pathological or protective correlates that are perturbed in disease, as well as their predicted drug targets, the AMC is envisioned to be critical in supporting the PMC and CRP in their goals of targeted therapeutics and precision, individualized treatments.

迄今为止，大多数现有的银屑病炎症的细胞或免疫学评价受到以下因素的限制： 用于分析的低分辨率数据通常依赖于总体临床终点。的总体目标 CORT将联合收割机新的生物信息学方法与先进的小鼠和人类实验方法相结合， 将科学发现转化为临床应用的方法， 银屑病和相关炎性共病。系统生物学提供了一种公正的方法， 对银屑病介导的炎症中涉及的宿主反应进行全面评估 这可能会导致新的治疗目标牛皮癣和理想的，那些为特定的病人。这 由现代高通量技术驱动的不断发展的调查范式， 数据集（“大数据”）的发展，产生了对集中式“组学”核心服务和分析平台的需求 CORT应用Meta'组学核心（AMC）将提供。AMC旨在作为一个创新的 与合作研究项目（CRP）有双向实验联系的合作资源， 临床前建模核心（PMC）。AMC将从CRP和PMC接收样本，生成 转录组学、代谢组学、微生物组和真菌组数据集，并提供生物信息学管道， 结合临床结局和/或其他数据类型分析这些数据集，包括纳入 人工智能、数据挖掘、网络技术和机器学习， 途径和差异表达的基因靶点，这将允许识别新的和/或重新用途的 毒品AMC通过以下目标支持CORT CRP的总体目标：（1）执行SOP驱动 PMC和CRP的样本采集、样本制备和组学测定;（2）鉴别差异 代谢组学、基因和途径表达特征，以及微生物/真菌组的变化， 来自人和银屑病样鼠模型的银屑病受累、未受累和对照皮肤的CRP;（3）（i） 确定系统生物学供体概况（内型）和候选生物标志物， 银屑病的发病机制在人类和小鼠模型和（ii）确定FDA批准的药物， 预测靶向与银屑病相关的生物标志物和/或途径。高度互动的核心 与中央CRP、AMC团队的专业知识、创新和广泛的资源协同互动 将推动CORT对银屑病理解和临床护理的转变和可持续影响。的 AMC将更深入地了解银屑病的病理事件，这可以转化为有针对性的 诊断和治疗策略，以管理银屑病在个人层面。通过组合 真菌/微生物组、代谢组学和转录组学分析，以确定病理或保护相关性 在疾病中受到干扰，以及它们预测的药物靶点，AMC被认为是至关重要的， 支持PMC和CRP实现其靶向治疗和精确的个体化治疗目标。