Semantic integration of protein epitopes and functional features for infectious and autoimmune disease knowledge discovery

项目摘要 免疫表位--被抗体和T细胞受体识别的抗原部分--是免疫系统的关键。 了解健康和异常的免疫反应。免疫表位数据库（IEDB）是一个免费的 由国家过敏和传染病研究所（NIAID）资助的可用资源， 在人类、非人类和哺乳动物中研究的超过一百万个抗体和T细胞表位的实验数据 灵长类动物和其他动物物种在感染性疾病、变态反应、自身免疫和 移植同样，在其他生物医学数据库中捕获的大量信息可以 可能应用于免疫学研究。这项工作的目标是整合免疫表位 从IEDB的信息与丰富的额外的生物医学数据在人类和模式生物，从而 为假说的产生和发现提供了新的机会。我们将无缝连接表位， UniProtKB中的蛋白质信息，包含丰富的功能注释和显示手段 蛋白质序列特征，以及蛋白质本体（PRO），它提供了同源信息和 Proteoforms的详细描述我们将进一步连接到专门研究蛋白质的资源 翻译后修饰（PTM），蛋白质-蛋白质相互作用，人类遗传变异，疾病， 毒品在UniProt ProtVista环境中以及通过IEDB网站显示此信息将使其 免疫学和疾病研究人员的大社区很容易获得。我们的工作将使小说 翻译研究人员高度感兴趣的查询，例如：（1）什么PTM和/或遗传变异重叠 与感兴趣的抗原表位结合确定这种重叠可以深入了解影响 自身抗原性或病原体的免疫逃避;（2）是否存在于 模式生物中的正向/同源蛋白质或反之亦然？这将使感兴趣的研究人员 人类疾病，充分利用来自模式生物的知识，反过来，改善疾病 非人类生物的模型。它还将能够识别内部的潜在交叉反应性， （3）在与自身抗原相互作用的蛋白质中是否有任何可药物靶点？ 与自身免疫性疾病相关的蛋白质这项工作的具体目标如下： 目标1.数据交换：在用例的指导下，我们将IEDB中的表位连接到PRO，UniProt， 和其他信息学资源;（二）目标2。信息获取：在用户输入的指导下，我们将加强 导航、数据可视化和应用程序接口，并在每个资源之间创建连接 （三）目标3。社区参与：我们将建立社区对互联资源的认识 并确保利益攸关方的需求得到反映。这是多个主要国家之间的合作努力， 资源将克服IEDB数据消费的障碍，从而支持调查的作用， 免疫系统在人类疾病中的作用

PROJECT SUMMARY Immune epitopes--the portions of an antigen that are recognized by antibodies and T-cell receptors--are key to understanding healthy and abnormal immune responses. The Immune Epitope Database (IEDB) is a freely available resource funded by the National Institute of Allergy and Infectious Diseases (NIAID) that catalogs experimental data on more than one million antibody and T cell epitopes studied in humans, non-human primates, and other animal species in the context of infectious disease, allergy, autoimmunity and transplantation. As well, there is a wealth of information captured in other biomedical databases that could potentially be applied to immunological research. The goal of this work is to integrate immune epitope information from IEDB with the wealth of additional biomedical data in humans and model organisms, thereby enabling novel opportunities for hypothesis generation and discovery. We will seamlessly connect epitopes to the protein information in UniProtKB, which contains rich functional annotation and the means to display protein sequence features, and the Protein Ontology (PRO), which provides orthology information and the explicit representation of proteoforms. We will make further connections to resources specializing in protein post-translational modifications (PTMs), protein-protein interactions, human genetic variation, diseases, and drugs. Display of this information in the UniProt ProtVista environment and via the IEDB website will make it easily accessible to the large community of immunology and disease researchers. Our work will enable novel queries of high interest to translational researchers, such as: (1) What PTMs and/or genetic variants overlap with an epitope of interest? Identification of such overlaps can provide insight into factors that affect auto-antigenicity or immune evasion by pathogens; (2) Is a human epitope of interest found in orthologous/homologous proteins in model organisms or vice-versa? This will allow researchers interested in human disease to fully exploit knowledge derived from model organisms, and conversely, improve disease models in non-human organisms. It will also enable identification of potential cross-reactivities within and across organisms; and (3) Are there any druggable targets among the proteins that interact with autoantigenic proteins associated with an autoimmune disease of interest? This work entails the following specific aims: (i) Aim 1. Data exchange: Guided by use cases, we will connect epitopes within IEDB to data from PRO, UniProt, and other informatics resources; (ii) Aim 2. Information access: Guided by user input, we will enhance navigation, data visualization, and application interfaces at each resource and create connections between them; and (iii) Aim 3. Community engagement: We will build community awareness of the connected resources and ensure that the needs of stakeholders are reflected. This collaborative effort among multiple major resources will overcome barriers to consumption of IEDB data, thereby supporting inquiry into the role of the immune system in human disease.