Micro-TeACH (Microbiome Technology and Analytic Center Hub)

摘要 尽管在该领域取得了许多进展，但自身免疫和免疫介导的疾病的发病机制仍不清楚。 （AIMD）仍然不完全了解，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， 是人体微生物组，即栖息在大多数身体部位和表面的微生物群落。 已知皮肤、口腔和肠道微生物组的扰动会诱导宿主免疫细胞活化， 下游炎症和持续的组织损伤，导致各种AIMD的发展。 在过去的三十年里，AIMD治疗也取得了根本性的进展。比如说， 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的临床结果，提高数百万患者的生活质量。不过尽管如此 一个重要的问题仍然没有答案：为什么超过50%的中度至重度患者 疾病对这些药物没有适当的反应？药物微生物学-一个新兴的研究领域， 研究人类肠道微生物组的变化对药物的影响-有望克服这些问题 并促进AIMD中的精准医学方法。此外，研究微生物组在 AMP-AIM网络通过高维分析进行疾病重建的目标背景 组织活检和样本将创造一个独特的机会， 和药物反应的预测因子。 由计算生物学家、风湿病学家、遗传学家和 微生物组研究人员，我们建议创建微教（微生物组技术和分析 中心枢纽），正式扩大了一个长期的纽约市为基础的合作博士Scher，赫盖伊（纽约大学 格罗斯曼医学院）和克莱门特（西奈山医学院），将整合专业知识， AIMD（RA、PSD和炎症性肠病）、广泛且表型良好的生物样本以及 AMP AIM的最先进的微生物组学方法的最终目标是：1）鉴定微生物和微生物 途径作为疾病发病机制的潜在决定因素; 2）询问宿主-微生物空间 受影响组织中的相互作用;以及3）发现基于微生物组的精准医学方法。 为了实现这些目标，我们将利用我们集团的独特资源， 软件管道、微生物生物学专业知识以及生物样本的数据/元数据和所有AMP积累的数据 AIM疾病团队，技术和分析核心，系统生物学核心和知识门户。这 这种方法应该提升AMP AIM计划的总体目标，该计划旨在获得全面的 了解分子和细胞疾病途径，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.