Rapid and Precise Molecular Pathway Modelling of the SARS-CoV-1 and SARS-CoV-2 Infection Cycle with Human Host Protein and Therapeutic Interactions

SARS-CoV-1 和 SARS-CoV-2 与人类宿主蛋白的感染周期和治疗相互作用的快速、精确的分子途径建模

• 批准号: 10165320
• 负责人: PETER G DEUSTACHIO
• 金额: $ 31.03万
• 依托单位: ONTARIO INSTITUTE FOR CANCER RESEARCH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10165320
• 关键词: 2019-nCoV; Authorship; Biological Process; COVID-19; Cells; Code; Collaborations; Communicable Diseases; Communities; Computer software; Consensus; Coronavirus; Coupled; Data; Data Analyses; Data Display; Data Set; Disease; Disease Pathway; Drug Design; Drug Targeting; Ensure; Future; Genomics; Human; Immune response; Infection; Innate Immune Response; Institutes; International; Link; Literature; Manuals; Maps; Mediating; Mining; Modeling; Molecular; Natural Immunity; Natural Language Processing; Network-based; Paper; Pathogenicity; Pathway interactions; Peer Review; Pharmaceutical Preparations; Process; Proteins; Proteome; Publishing; Reaction; Research; Resources; SARS coronavirus; Severities; Source; System; Systems Biology; Therapeutic; Therapeutic Effect; Therapeutic Monoclonal Antibodies; Variant; Viral; Viral Proteins; Virus; Virus Diseases; Work; adaptive immunity; data integration; data structure; data tools; data visualization; experimental analysis; knowledge base; open source; protein expression; small molecule; structured data; tool; virology

Project Summary The Reactome Knowledgebase is a widely used and internationally recognized expert-curated, open-source resource of a broad array of human biological processes and their disease counterparts, coupled to powerful tools for data analysis and display, and integrated with diverse community genomics resources. The work proposed here will add molecular annotations of the COVID-19 infection process mediated by the SARS-CoV-2 coronavirus, interactions between viral components and human host proteins that mediate the severity of viral infection, and the effects of therapeutics and drug-like compounds on both viral and host proteins. The resulting SARS-CoV-2 pathway annotations will provide a framework for pathway- and network-based data analysis and visualization, which will be critical for the interpretation of numerous COVID-19 studies now and in the future. In collaboration with a team of community experts in virology, drug design, and infectious disease, we will assemble information in two stages. First, a draft annotation will associate relevant SARS-CoV-1 and SARS-CoV- 2 viral and host cell proteins with each stage of the infection process and the host response to it. These annotations will be immediately useful for identifying additional relevant interacting proteins, for assessing possible effects of variation in the host or viral proteins on specific steps of viral infection, and for identifying possible drug targets. In the second stage, the SARS-CoV-2 map will be annotated more extensively to fill in molecular details of each step in these processes and to highlight differences in the processes mediated by SARS- CoV-2 virus and related coronaviruses. This annotation process will continue for the duration of the project to incorporate newly validated molecular details as they are uncovered by the research community. All the data, code and tools developed by this project will be open source and open.

项目摘要 Reactome知识库是一个广泛使用和国际公认的专家策划的开源 人类生物过程及其疾病对应物的广泛资源，加上强大的工具， 用于数据分析和显示，并与不同的社区基因组学资源相结合。工作提出的 这里将添加SARS-CoV-2介导的COVID-19感染过程的分子注释 冠状病毒，病毒成分和人类宿主蛋白质之间的相互作用，介导病毒的严重性， 感染，以及治疗剂和药物样化合物对病毒和宿主蛋白的作用。所得 SARS-CoV-2途径注释将为基于途径和网络的数据分析提供框架， 可视化，这将是至关重要的许多COVID-19研究的解释现在和未来。 与病毒学、药物设计和传染病方面的社区专家团队合作，我们将 将信息分为两个阶段。首先，一份注释草案将相关的SARS-CoV-1和SARS-CoV-1联系起来， 2病毒和宿主细胞蛋白与感染过程的每个阶段和宿主对其的反应。这些 注释将立即用于识别额外的相关相互作用蛋白，用于评估 宿主或病毒蛋白质的变异对病毒感染的特定步骤的可能影响， 可能的药物靶点在第二阶段，SARS-CoV-2图谱将被更广泛地注释以填充 这些过程中每个步骤的分子细节，并强调SARS介导的过程中的差异， CoV-2病毒和相关冠状病毒。这一注释过程将在项目期间继续进行， 结合新验证的分子细节，因为它们是由研究界发现的。 该项目开发的所有数据、代码和工具都将是开源和开放的。

项目成果

Biomedical Informatics on the Cloud: A Treasure Hunt for Advancing Cardiovascular Medicine.

云上的生物医学信息学：一种用于推进心血管医学的寻宝活动。

• DOI: 10.1161/circresaha.117.310967
• 发表时间: 2018-04-27
• 期刊: Circulation research
• 影响因子: 20.1
• 作者: Ping P;Hermjakob H;Polson JS;Benos PV;Wang W
• 通讯作者: Wang W

VaximmutorDB: A Web-Based Vaccine Immune Factor Database and Its Application for Understanding Vaccine-Induced Immune Mechanisms.

• DOI: 10.3389/fimmu.2021.639491
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Berke K;Sun P;Ong E;Sanati N;Huffman A;Brunson T;Loney F;Ostrow J;Racz R;Zhao B;Xiang Z;Masci AM;Zheng J;Wu G;He Y
• 通讯作者: He Y

Installing a Local Copy of the Reactome Web Site and Knowledgebase.

• DOI: 10.1002/0471250953.bi0910s50
• 发表时间: 2015-06-19
• 期刊: Current protocols in bioinformatics
• 作者: McKay SJ;Weiser J
• 通讯作者: Weiser J

ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis.

ReactomeGSA-有效的多摩斯比较途径分析。

• DOI: 10.1074/mcp.tir120.002155
• 发表时间: 2020-12
• 期刊: Molecular & cellular proteomics : MCP
• 作者: Griss J;Viteri G;Sidiropoulos K;Nguyen V;Fabregat A;Hermjakob H
• 通讯作者: Hermjakob H

Evaluating the predictive accuracy of curated biological pathways in a public knowledgebase.

• DOI: 10.1093/database/baac009
• 发表时间: 2022-03-28
• 期刊: Database : the journal of biological databases and curation