Micro-TeACH (Microbiome Technology and Analytic Center Hub)

摘要 尽管该领域取得了许多进展，但自身免疫和免疫介导性疾病的发病机制 (AIMDS)仍不完全了解，但似乎是多因素的；遗传和环境因素 与许多AIMD的异常炎症反应有关，包括狼疮、类风湿性关节炎(RA)、 银屑病谱系疾病(PSD)和干燥综合征(SS)。在这些疾病的潜在诱因中 是人类的微生物群落，即生活在大多数身体部位和表面的微生物群落。 已知皮肤、口腔和肠道微生物群的扰动会诱导宿主免疫细胞激活， 下游炎症和持续的组织损伤，促进了各种AIMD的发展。 在过去的三十年里，AIMD疗法也取得了根本性的进步。例如, 甲氨蝶呤的使用和随后的生物治疗的结合导致了实质性的改善 在RA和PSD临床结果方面，提高了数百万患者的生活质量。然而尽管如此， 进展一个重要的问题仍然没有得到回答：为什么超过50%的中到重度患者 疾病对这些药物没有适当的反应吗？药物微生物学--一个新兴的研究领域 研究人类肠道微生物群的变异对药物的影响--有望克服这些 障碍和促进AIMD的精准医学方法。进一步地，研究海洋中的微生物群 AMP-AIM网络通过高维分析重建疾病的目标的背景 组织活检和样本将创造一个独特的机会，将潜在的免疫激活触发因素结合在一起 以及药物反应的预测因子。 拥有一个由计算生物学家、风湿学家、遗传学家和 微生物组研究人员，我们建议创建Microteach(微生物组技术和分析 Center Hub)，正式扩展了Scher博士、Hguy博士(纽约大学)之间在纽约的长期合作 格罗斯曼医学院)和克莱门特(西奈山医学院)将整合 AIMD(类风湿性关节炎、PSD和炎症性肠病)、广泛且表型良好的生物样本，以及 最先进的微生物学方法用于AMP目的最终目的：1)鉴定微生物和微生物 作为疾病发病机制潜在决定因素的途径；2)询问宿主-微生物空间 在受影响的组织中的相互作用；以及3)发现基于微生物组的精确医学方法。 为了实现这些目标，我们将利用我们集团可用的独特资源，并整合我们的 软件管道、微生物专业知识以及所有AMP收集的生物样本和数据的数据/元数据 目标疾病团队，技术和分析核心，系统生物学核心和知识门户。这 方法应提升AMP AIM计划的总体目标，该计划寻求获得全面的 了解分子和细胞疾病的途径，并确定新的干预目标。

ABSTRACT Despite many advances in the field, the pathogenesis of autoimmune and immune-mediated diseases (AIMDs) remains incompletely understood but appears to be multifactorial; genetic and environmental factors are implicated in the aberrant inflammatory responses in many AIMDs, including lupus, rheumatoid arthritis (RA), psoriatic spectrum diseases (PSD) and Sjogren’s syndrome (SS). Among potential triggers for these disorders is the human microbiome, the communities of microorganisms that inhabit most body sites and surfaces. Perturbations in the the skin, oral and gut microbiome are known to induce host immune cell activation, downstream inflammation, and persistent tissue damage, contributing to the development of various AIMDs. The last three decades have also witnessed fundamental advances in AIMD therapeutics. For example, the use of methotrexate and subsequent incorporation of biologic treatments has led to substantial improvements in RA and PSD clinical outcomes, enhancing the quality of life for millions of patients. However, despite this progress a significant question remains unanswered: why do over 50% of patients with moderate to severe disease fail to respond appropriately to these agents? Pharmacomicrobiomics – an emerging field of study that investigates the effects of variations of the human gut microbiome on drugs – promises to overcome these barriers and facilitate precision medicine approaches in AIMDs. Further, studying the microbiome in the context of the AMP-AIM Network’s goal of disease reconstruction through high dimensional analytics of tissue biopsies and samples will create a unique opportunity to incorporate potential triggers of immune activation and predictors of drug response. With a multidisciplinary team composed of computational biologists, rheumatologists, geneticists, and microbiome researchers, we propose the creation of Micro-TeACH (Microbiome Technology and Analytic Center Hub), a formal expansion of a longstanding NYC-based collaboration between Drs. Scher, Heguy (NYU Grossman School of Medicine) and Clemente (Mount Sinai School of Medicine) that will integrate expertise in AIMDs (RA, PSD and inflammatory bowel disease), extensive and well-phenotyped biosamples, and state-of- the-art microbiomics methods to AMP AIM with the ultimate goals of: 1) identifying microbes and microbial pathways as potential determinants of disease pathogenesis; 2) interrogating host-microbe spatial interactions in affected tissues; and 3) discovering microbiome-based precision medicine approaches. To achieve these goals, we will utilize the unique resources available to our groups and integrate our software pipelines, microbiomics expertise, and data/metadata with biosamples and data accrued by all AMP AIM Disease Teams, Technology and Analytic Cores, System Biology Cores and Knowledge Portal. This approach should elevate the overarching aim of the AMP AIM Program, which seeks to gain a comprehensive understanding of molecular and cellular disease pathways and to identify novel targets for intervention.