ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways.
ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways.
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ViralLink：研究SARS-CoV-2对细胞内信号传导和调控途径影响的综合工作流程。
DOI：
10.1371/journal.pcbi.1008685
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发表时间：
2021-03
影响因子：
4.3
通讯作者：
Korcsmaros T
中科院分区：
文献类型：
--
作者：
Treveil A;Bohar B;Sudhakar P;Gul L;Csabai L;Olbei M;Poletti M;Madgwick M;Andrighetti T;Hautefort I;Modos D;Korcsmaros T
2020年的SARS-CoV-2大流行动员了全球科学家对冠状病毒病毒及其感染的方方面面进行研究。为了对病毒致病机制进行卓有成效的快速研究，需要一种协作和跨学科的方法。因此，我们开发了ViralLink：一种系统生物学工作流程，它重建和分析代表病毒对细胞内信号影响的网络。这些网络跟踪细胞内病毒蛋白通过其人类结合蛋白和下游信号通路的信号流，以转录因子调节病毒暴露时差异表达的基因结束。通过这种方式，工作流程从先前识别的病毒感染细胞的知识中提供了机械性的洞察。默认情况下，工作流程被设置为分析SARS-CoV-2的细胞内影响，只需要将转录计数数据作为用户的输入：因此，鼓励和支持快速的多学科研究。然而，工作流程的广泛适用性和模块化促进了病毒环境、先验交互和分析方法的定制。通过SARS-CoV-2感染的支气管/气管上皮细胞的案例研究，我们证明了工作流程的功能及其在细胞对感染的反应中识别关键路径和蛋白质的能力。使用不同的可用转录数据集，以特定的上下文方式将ViralLink应用于不同的病毒感染，将揭示病毒致病的关键机制。
The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is required. Therefore, we have developed ViralLink: a systems biology workflow which reconstructs and analyses networks representing the effect of viruses on intracellular signalling. These networks trace the flow of signal from intracellular viral proteins through their human binding proteins and downstream signalling pathways, ending with transcription factors regulating genes differentially expressed upon viral exposure. In this way, the workflow provides a mechanistic insight from previously identified knowledge of virally infected cells. By default, the workflow is set up to analyse the intracellular effects of SARS-CoV-2, requiring only transcriptomics counts data as input from the user: thus, encouraging and enabling rapid multidisciplinary research. However, the wide-ranging applicability and modularity of the workflow facilitates customisation of viral context, a priori interactions and analysis methods. Through a case study of SARS-CoV-2 infected bronchial/tracheal epithelial cells, we evidence the functionality of the workflow and its ability to identify key pathways and proteins in the cellular response to infection. The application of ViralLink to different viral infections in a context specific manner using different available transcriptomics datasets will uncover key mechanisms in viral pathogenesis.
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