实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (4): 357-373.DOI: 10.12300/j.issn.1674-5817.2024.008

• 人类疾病动物模型 • 上一篇    下一篇

冠状病毒感染动物模型组学数据集成分析

吴玥1(), 李璐2, 张阳2, 王珏1, 冯婷婷1, 李依桐1, 王凯2, 孔琪1()()   

  1. 1.中国医学科学院医学实验动物研究所, 国家人类疾病动物模型资源库, 国家动物模型技术创新中心, 国家卫生健康委员会比较医学重点实验室, 新发再发传染病动物模型研究北京市重点实验室, 北京市人类重大疾病实验动物模型工程技术研究中心, 北京 100021
    2.上海宇道生物技术有限公司, 上海 201210
  • 收稿日期:2024-01-16 修回日期:2024-04-10 出版日期:2024-09-06 发布日期:2024-08-25
  • 通讯作者: 孔琪(1978—),男,博士,研究员,研究方向:比较医学及生物信息学。E-mail: kongqi@cnilas.org。ORCID: 0000-0003-2867-7382
  • 作者简介:吴玥(1993—),女,硕士,助理研究员,研究方向:比较医学及相关数据库建设。E-mail: wuyue@cnilas.org。ORCID: 0000-0001-5874-8263
    孔 琪,医学博士,研究员,硕士生导师。现任中国医学科学院医学实验动物研究所生物信息研究中心负责人、课题组长,曾任所长助理。兼任中国实验动物学会实验动物标准化技术委员会秘书长、全国实验动物标准化技术委员会前任秘书长暨现任委员。长期从事实验动物大数据、标准化和学科体系建设,主持或参与国家863项目、科技重大专项、卫生行业专项、北京市自然科学基金面上项目等20余项课题研究,组织开发12个实验动物与比较医学大数据平台或数据库,发表科技文章60余篇,其中SCI论文18篇。同时,参与策划编写国家统编研究生教材、医学八年制教材、北京协和医学院特色研究生教材、实验动物科学系列丛书等,作为副主编或编委参编教材或专著23部;主编或参编国家标准12项,团体标准20项。获得教育部、中国实验动物学会等科技奖励8项,以及中国实验动物学会科学技术奖优秀青年人才奖、中国标准化战略联盟标准化专家等荣誉。(ORCID: 0000-0003-2867-7382), E-mail: kongqi@cnilas.org
  • 基金资助:
    北京市自然科学基金资助项目“基于大数据的新型冠状病毒肺炎动物模型数据库建立”(M21027);国家重点研发计划重点项目“国家实验动物资源库服务科技创新能力提升关键技术研究与示范”(2021YFF0702800)

Integrative Analysis of Omics Data in Animal Models of Coronavirus Infection

WU Yue1(), LI Lu2, ZHANG Yang2, WANG Jue1, FENG Tingting1, LI Yitong1, WANG Kai2, KONG Qi1()()   

  1. 1.Institute of Laboratory Animal Science, CAMS & PUMC, National Human Diseases Animal Model Resource Center, National Center of Technology Innovation for Animal Model, NHC Key Laboratory of Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China
    2.Nutshell Therapeutics Co. , Ltd. , Shanghai 201210, China
  • Received:2024-01-16 Revised:2024-04-10 Published:2024-08-25 Online:2024-09-06
  • Contact: KONG Qi (ORCID: 0000-0003-2867-7382), E-mail: kongqi@cnilas.org

摘要:

目的 分析各个公共数据库中可感染人的冠状病毒感染动物模型的组学数据资源情况,包括数据分布、数据集数量、数据类型、物种、品系、研究内容等,从而深入理解冠状病毒的生物学特征和致病机制,为研究有效的治疗方案和预防措施奠定基础。 方法 定义特定病毒名称、时间范围和物种等检索策略与纳入排除标准,检索GEO、ArrayExpress等大型公共组学数据库。根据不同字段类型进行二次过滤,获取更精确的数据列表。建立组学数据文本库,进行文献计量学分析,构建共现网络图,分析不同研究主题、技术方法和涉及物种之间的关联强度。同时,分析研究涉及的细胞类型、器官和参与的生物途径,以进一步阐明病原体与宿主之间的致病相互作用。 结果 含有冠状病毒组学数据的公共数据库有20余个,以新型冠状病毒感染组学数据为主。常用物种为人、小鼠、仓鼠和猴,常用病毒株为Wuhan-Hu-1和USA-WA1/2020。此外,人类相关研究主要集中于气道上皮细胞和Calu-3细胞,动物模型(如小鼠、猕猴与雪貂)则多采用肺组织。表达谱数据显示感染后参与炎症、细胞因子反应、补体途径、细胞损伤、增殖和分化等通路基因显著上调。蛋白组学研究揭示,在不同感染阶段的患者样本中磷酸化蛋白质组、泛素组和全蛋白质组具有显著变化。特定蛋白质类别,包括病毒受体和蛋白酶、转录因子、细胞因子、凝血系统相关蛋白、血管生成相关蛋白及纤维化标志物等六类蛋白均在冠状病毒感染后发生改变。此外,代谢组数据提示磷酸胆碱、磷酸乙醇胺、花生四烯酸和油酸可作为潜在的代谢标志物。表观组学研究结果显示,m6A甲基化在新冠病毒复制、感染和传播过程中发挥作用,并且对宿主细胞-病毒互作产生影响。N、S、非结构蛋白2和3泛素化最为显著。微生物组学研究趋势表明,肠道和废水中的微生物群落正在成为新的研究重点。 结论 冠状病毒组学数据类型丰富,模型与细胞类型多样。根据不同病毒的特征,造模物种和技术方法的选择具有差异性。研究冠状病毒感染动物模型的多组学数据可以揭示宿主-病原体之间的关键相互作用,发现生物标志物和潜在的治疗靶点,为深入理解冠状病毒的生物学特性和感染机制提供丰富信息。

关键词: 冠状病毒感染, 动物模型, 组学数据, SARS-CoV-2, SARS-CoV, MERS-CoV, 集成分析

Abstract:

Objective This study analyzes the omics data resources in human-infecting coronavirus animal models collected from various public databases, focusing on data distribution, dataset quantity, data types, species, strains, and research content. It aims to enhance our understanding of biological characteristics and pathogenic mechanisms of coronaviruses, thereby providing a solid foundation for devising effective therapeutic strategies and preventive measures. Methods Query strategies, including specific virus names, time ranges, and inclusion and exclusion criteria, were defined to retrieve data from major public omics databases such as GEO and ArrayExpress. Secondary filtering was performed based on different field types to obtain a more accurate data list. An omics data text database was established for bibliometric analysis. Co-occurrence networks were constructed for the analysis of the correlation strengths between different research themes, technical methods, and involved species. The cell types, organs, and biological pathways involved in studies were examined to further elucidate the pathogenic interplay between pathogens and hosts. Results About twenty public databases containing coronavirus-related omics data were identified, with a primary focus on novel coronavirus infection. Commonly used species include humans, mice, hamsters, and monkeys, while the commonly used virus strains are Wuhan-Hu-1 and USA-WA1/2020. Lung tissues are primarily used in animal models such as mice, macaques, and ferrets, while airway epithelial cells and Calu-3 cells are predominantly employed in human-related studies. Expression profiling data indicate that gene pathways involved in inflammation, cytokine response, complement pathway, cell damage, proliferation, and differentiation are significantly upregulated after infection. Proteomics studies reveal significant changes in phosphoproteome, ubiquitinome, and total proteome of patient samples at different infection stages. Specific protein categories, including viral receptors and proteases, transcription factors, cytokines, proteins associated with coagulation system, angiogenesis-related proteins, and fibrosis markers, show alterations after coronavirus infection. In addition, metabolomics data suggest that phosphocholine, phosphoethanolamine, arachidonic acid, and oleic acid could serve as potential metabolic markers. Epigenomics research indicates m6A methylation plays a role in SARS-CoV-2 replication, infection, and transmission, affecting host cell-virus interactions. Among these, N, S, and non-structural proteins 2 and 3 exhibit the most significant ubiquitination. Trends in microbiomics research suggest that microbial communities in the gut and wastewater are emerging as new research focuses. Conclusion The data types of coronavirus omics are diverse, with a wide variety of models and cell types used. The selection of species and technical methods for modelling varies based on the characteristics of different viruses. Multi-omics data from animal models of coronavirus infection can reveal key interactions between hosts and pathogens, identifying biomarkers and potential therapeutic targets, and provide valuable information for a deeper understanding of biological characteristics and infection mechanisms of coronaviruses.

Key words: Coronavirus infection, Animal models, Omics data, SARS-CoV-2, SARS-CoV, MERS-CoV, Integrative analysis

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