Core 2: Applied Meta'Omics Core

到目前为止，大多数现有的银屑病炎症的细胞或免疫学评估都受到以下因素的限制 用于分析的低分辨率数据，通常依赖于粗略的临床终点。该计划的总体目标 CORT将把新的生物信息学方法与先进的老鼠和人类实验相结合 将科学发现转化为临床应用的方法，以更灵活地推进治疗 牛皮癣和相关的炎症性并存。系统生物学提供了一种公正的方法来 对银屑病介导的炎症中涉及的宿主反应进行全面评估 这可能会导致牛皮癣的新治疗目标，理想情况下，是为特定患者量身定做的目标。这 由现代高通量技术推动的不断发展的调查范式，产生了巨大的 数据集(“大数据”)催生了对集中的‘组学核心服务和分析平台’的需求 CORT应用Meta‘Omics Core(AMC)将提供的。AMC旨在作为一种创新的 具有双向实验的协作资源与协作研究项目(CRP)和 临床前建模核心(PMC)。AMC将从CRP和PMC接收样本，生成 转录组、代谢组、微生物组和真菌组数据集，并提供生物信息管道 结合临床结果和/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使识别新奇事物成为可能 将允许识别新的和/或重新用途的途径和差异表达的基因靶点 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的样品采集、样品制备和组学分析；(2)识别差异 代谢、基因和途径表达特征，以及微生物/真菌生物群的变化 银屑病患者、非银屑病患者和对照皮肤中CRP的检测；(3)(I) 确定系统生物学供体轮廓(内型)和可能定义 牛皮癣在人和小鼠模型中的发病机制以及(Ii)确定FDA批准的药物 预计将针对与牛皮癣相关的生物标记物和/或途径。高度交互的核心 与中央CRP、AMC团队的专业知识、创新和广泛资源协同互动 将推动CORT对牛皮癣的理解和临床护理产生变革和可持续的影响。这个 AMC将更深入地了解牛皮癣的病理事件，这可以转化为靶向 在个人层面上管理牛皮癣的诊断和治疗策略。通过组合 真菌/微生物组、代谢组和转录组分析以确定病理或保护性相关因素 以及他们预测的药物靶点，AMC被设想在 支持PMC和CRP实现靶向治疗和精确、个性化治疗的目标。

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.