Influenza host specific glycan motif identification through systems biology

通过系统生物学鉴定流感宿主特异性聚糖基序

• 批准号: 9895377
• 负责人: XIUFENG HENRY WAN
• 金额: $ 23.97万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895377
• 关键词: Affect; Animals; Antibodies; Area; Avian Influenza A Virus; Binding; Binding Sites; Biological; Biological Assay; Biosensor; Birds; Canis familiaris; Code; Complex; Computing Methodologies; Data; Data Set; Development; Domestic Fowls; Equus caballus; Family suidae; Goals; Growth; Hemagglutinin; Human; Immune Sera; Infection; Influenza; Influenza A virus; Influenza prevention; Knowledge; Learning; Lectin; Life; Link; Mammals; Methods; Molecular; Monitor; Mutation; National Institute of Allergy and Infectious Disease; Natural History; Pathogenesis; Performance; Play; Polysaccharides; Property; Proteins; Public Health; Research; Resources; Risk; Role; Sea; Sialic Acids; Signal Transduction; Slide; Strategic Planning; Streptavidin; Structure; Systems Biology; Technology; Testing; Tissues; Trees; Tropism; United States National Institutes of Health; Validation; Variant; Virus Diseases; Zoonoses; base; carbohydrate receptor; carbohydrate structure; computerized tools; design; experimental study; flu transmission; improved; in silico; influenza virus vaccine; influenzavirus; large datasets; learning strategy; machine learning method; microorganism; multi-task learning; multitask; novel; pathogen; prevent; protein profiling; receptor; receptor binding; respiratory; response; swine influenza; tissue tropism; tool; transmission process; universal influenza vaccine; viral transmission; wild bird

Project Summary Influenza A viruses (IAVs) have caused large losses of life around the world and continue to present a great public health challenge. IAVs can cause infections in birds, sea mammals, lower mammals (e.g., pigs, dogs, and horses), and humans. Previous studies have demonstrated that the structures of the carbohydrate receptors determine influenza host and tissue tropisms. Thus, it is necessary to understand the receptor- binding properties for IAVs and monitor changes to them, especially for IAVs at the animal–human interface. However, this understanding is hampered by our lack of detailed knowledge of IAV glycan substructures; most of our knowledge is limited to SA2,3Gal-like and SA2,6Gal-like structures. The goals of this project are to develop and validate a machine learning method to identify host-specific glycan substructures for IAVs by using glycan array data and to identify and validate the glycan motifs associated with the host tropisms of IAVs, including those for zoonotic IAVs. The study will focus on natural hosts of IAVs: humans, swine, canines, equines, and various avian species, including common domestic poultry species and wild bird species. We expect to identify structural determinants for receptor binding with human-, swine-, canine-, and avian-origin IAVs. Such knowledge will help us understand the factors that contribute to influenza infection and transmission and thereby facilitate development of an effective influenza vaccine to prevent virus infection and block virus transmission. This knowledge will also help us develop rapid assays for monitoring emerging influenza threats at the animal–human interface. We also expect to develop a computational method for identifying glycan motifs associated with influenza host tropisms; this method will be able to be adapted to determine functional glycan motifs for other proteins, lectins, antibodies, antisera, and microorganisms, including those of other infectious pathogens, by using glycan arrays.

项目摘要 流感病毒（IAVS）在世界范围内造成了巨大的生活损失，并继续呈现出伟大的 公共卫生挑战。 IAV可以引起鸟类，海哺乳动物，下哺乳动物（例如猪，狗， 和马）和人类。先前的研究表明，碳水化合物的结构 受体确定影响Za宿主和组织的偏向主义。那是有必要理解受体的 IAVS的结合特性并监测其变化，尤其是对于动物 - 人类界面处的IAV。 但是，由于缺乏对IAV聚糖子结构的详细了解，这种理解受到了阻碍。最多 我们的知识仅限于SA2,3Gal样和SA2,6Gal样结构。该项目的目标是 开发和验证一种机器学习方法，以通过 使用聚糖阵列数据并识别和验证与IAVS宿主向Tropism相关的聚糖基序， 包括人畜共患病。该研究将重点关注IAV的自然寄主：人类，猪，犬， 马和各种鸟类，包括常见的家禽和野生鸟类。 期望鉴定与人，猪，犬和鸟素结合的受体结合的结构决定剂 IAVS。这些知识将帮助我们了解导致影响力感染的因素和 传播，从而喜欢开发有效影响疫苗，以防止病毒感染和 阻断病毒传播。这些知识还将帮助我们开发快速的测定法以监视新兴 影响力 - 人类界面的影响力威胁。我们还期望为 识别与影响力宿主往流相关的聚糖基序；此方法将能够适应 确定其他蛋白质，凝集素，抗体，抗血清和微生物的功能性聚糖基序， 包括其他传染病病原体，包括使用聚糖阵列。