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InSIGHT: Integrating Statistical methods, Immunology and Genomics for Healthcare Translation

InSIGHT：整合统计方法、免疫学和基因组学进行医疗保健翻译

基本信息

批准号：
MR/W018861/1
负责人：
Kenneth Smith
金额：
$ 284.9万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FW018861%2F1
关键词：
InSIGHT Integrating Statistical methods Immunology

项目摘要

Diseases caused by a malfunction of the immune system are common and can be severe. They include multiple sclerosis (MS) and inflammatory bowel disease (IBD: Crohn's and ulcerative colitis), among many others. They are incurable, often occur in young adulthood, and effect up to 10% of the population at some time in their lives. We are now able to analyse samples from patients with these diseases, and produce datasets of unprecedented detail. Our challenge is to use this information to increase our understanding of disease, and to deliver tests to help guide patient treatment and improve outcome. Our previous MRC programme grant had begun this process through analysis of patient data collected since 2004, which led to a test which predicts long-term outcome in IBD - this is now available to patients to inform them of their likely disease behaviour and to help guide treatment. This grant also funded the development of new, enlarged patient cohorts encompassing different immune diseases: MS, IBD (both Crohn's and UC), SLE, ANCA-associated vasculitis and idiopathic pulmonary fibrosis. We now propose to exploit this newly created resource by developing "integrative analysis" methods to make sense of the data we have collected. These use AI (artificial intelligence, or machine learning) to analyse across different sorts of data (including things such as immune cell numbers, blood protein levels and disease activity scores) and different diseases over time, drawing strength from the complexity of the data collected. In addition to the diseases listed above, for comparison we have also included a cohort of patients with severe COVID-19, all of whom have severe inflammation and over 10% of whom also have autoimmunity (evidence of the immune system directly targeting the patient). This promises to lead to new insights into what drives disease, and importantly also to the development of further tests to help predict disease outcome and help guide patient treatment. This work will produce publicly available data and new analysis pipelines to support future research by the scientific community, will train young researchers in cutting edge methods, but should also tests of practical value to patients in the clinic - hoping to achieve "personalised medicine" by allowing patient management to be tailored to individual patient needs.

由免疫系统故障引起的疾病很常见，而且可能很严重。它们包括多发性硬化症（MS）和炎症性肠病（IBD：克罗恩病和溃疡性结肠炎）等。它们是不可治愈的，通常发生在年轻的成年人，并在他们生命中的某个时候影响高达10%的人口。我们现在能够分析这些疾病患者的样本，并生成前所未有的详细数据集。我们面临的挑战是利用这些信息来增加我们对疾病的理解，并提供测试来帮助指导患者治疗和改善结果。我们之前的MRC计划拨款已经通过分析自2004年以来收集的患者数据开始了这一过程，这导致了一项预测IBD长期结果的测试-现在患者可以告知他们可能的疾病行为并帮助指导治疗。这笔赠款还资助了新的、扩大的患者队列的开发，包括不同的免疫疾病：MS、IBD（克罗恩病和UC）、SLE、ANCA相关血管炎和特发性肺纤维化。我们现在建议通过开发“综合分析”方法来利用这一新创建的资源，以使我们收集的数据有意义。这些技术使用人工智能（人工智能或机器学习）来分析不同类型的数据（包括免疫细胞数量、血液蛋白水平和疾病活动评分等）以及随着时间的推移而发生的不同疾病，从收集的数据的复杂性中汲取力量。除上述疾病外，为了进行比较，我们还纳入了一组患有严重COVID-19的患者，所有患者均患有严重炎症，其中超过10%还患有自身免疫（免疫系统直接靶向患者的证据）。这有望导致对疾病驱动因素的新见解，重要的是还可以开发进一步的测试，以帮助预测疾病结果并帮助指导患者治疗。这项工作将产生公开可用的数据和新的分析管道，以支持科学界未来的研究，将培训年轻的研究人员掌握尖端方法，但也应该对临床患者进行具有实用价值的测试-希望通过允许患者管理来实现“个性化医疗”，以适应个体患者的需求。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

B cell receptor repertoire kinetics after SARS-CoV-2 infection and vaccination.

SARS-CoV-2 感染和疫苗接种后 B 细胞受体库动力学。

DOI：
10.17863/cam.82380
发表时间：
2022
期刊：
影响因子：
0
作者：
Kotagiri P
通讯作者：
Kotagiri P

The impact of hypoxia on B cells in COVID-19.

DOI：
10.1016/j.ebiom.2022.103878
发表时间：
2022-03
期刊：
EBioMedicine
影响因子：
11.1
作者：
Kotagiri P;Mescia F;Hanson AL;Turner L;Bergamaschi L;Peñalver A;Richoz N;Moore SD;Ortmann BM;Dunmore BJ;Morgan MD;Tuong ZK;Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration;Göttgens B;Toshner M;Hess C;Maxwell PH;Clatworthy MR;Nathan JA;Bradley JR;Lyons PA;Burrows N;Smith KGC
通讯作者：
Smith KGC

miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.

miR-374a-5p 调节炎症性肠病患者的炎症基因和单核细胞功能。