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

项目总结 免疫表位--被抗体和T细胞受体识别的抗原部分--是关键 了解健康和异常的免疫反应。免疫表位数据库是一个免费的数据库 由国家过敏和传染病研究所(NIAID)资助的可用资源，该目录 在人类和非人类中研究的100多万个抗体和T细胞表位的实验数据 灵长类和其他动物物种在传染病、过敏、自身免疫和 移植。此外，在其他生物医学数据库中捕获的大量信息也可能 有可能应用于免疫学研究。这项工作的目标是整合免疫表位 来自IEDB的信息和丰富的人类和模型生物的额外生物医学数据，从而 为假说的产生和发现提供了新的机会。我们将把表位无缝连接到 UniProtKB中的蛋白质信息，包含丰富的功能标注和展示手段 蛋白质序列特征，以及蛋白质本体论(PRO)，它提供正构学信息和 蛋白质形式的显式表示。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、疾病和 毒品。在UniProt ProtVista环境中和通过IEDB网站显示这些信息将使 对于免疫学和疾病研究人员的大型社区来说，很容易获得。我们的工作将使小说 翻译研究人员非常感兴趣的问题，例如：(1)PTM和/或基因变体有哪些重叠 带着感兴趣的表位？识别这样的重叠可以提供对影响 自身抗原性或病原体的免疫逃避；(2)是人类感兴趣的表位，发现于 模式生物中的同源/同源蛋白质还是反之亦然？这将使研究人员对 人类疾病，充分利用来自模型生物的知识，反过来，改善疾病 在非人类生物体中的模型。它还将使识别潜在的交叉反应在和 跨生物体；以及(3)在与自身抗原相互作用的蛋白质中是否存在可用药的靶点 与感兴趣的自身免疫性疾病相关的蛋白质？这项工作的具体目标如下：(I) 目标1.数据交换：在用例的指导下，我们将IEDB中的表位与来自PRO、UniProt、 和其他信息学资源；(2)目标2.信息获取：以用户意见为导向，我们将加强 每个资源的导航、数据可视化和应用程序接口，并在 目标3.社区参与：我们将建立社区对相关资源的认识 并确保利益相关者的需求得到反映。多家主要企业之间的协作努力 资源将克服使用研究所数据的障碍，从而支持对研究所的作用的调查 人类疾病中的免疫系统。

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.