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知识基础是广泛使用且具有国际认可的专家策划的开源 广泛的人类生物过程及其疾病的资源，与强大的工具相结合 用于数据分析和显示，并与各种社区基因组学资源集成。提出的工作 这里将添加由SARS-COV-2介导的COVID-19感染过程的分子注释 冠状病毒，病毒成分与人类宿主蛋白之间介导病毒严重程度的相互作用 感染，以及治疗剂和类似药物的化合物对病毒和宿主蛋白的影响。结果 SARS-COV-2途径注释将为基于途径和网络的数据分析和 可视化，这对于现在和将来的众多Covid-19研究至关重要。 与病毒学，药物设计和传染病的社区专家团队合作，我们将 在两个阶段组装信息。首先，注释草案将使相关的SARS-COV-1和SARS-COV与 2病毒和宿主细胞蛋白具有感染过程的每个阶段以及宿主对其的反应。这些 注释将立即用于识别其他相关的相互作用蛋白，以评估评估 宿主或病毒蛋白变异对病毒感染的特定步骤的可能影响，并用于识别 可能的药物靶标。在第二阶段，SARS-COV-2地图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，并突出由SARS介导的过程中的差异 COV-2病毒和相关冠状病毒。该注释过程将在项目期间继续 在研究界发现了新近验证的分子细节。 该项目开发的所有数据，代码和工具将是开源和打开的。

项目成果

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

• 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

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

ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis.

• 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