PDF(Pubmed)
Abstract：
Establishing consensus around the transcriptional interface between coronavirus (CoV) infection and human cellular signaling pathways can catalyze the development of novel anti-CoV therapeutics. Here, we used publicly archived transcriptomic datasets to compute consensus regulatory signatures, or consensomes, that rank human genes based on their rates of differential expression in MERS-CoV (MERS), SARS-CoV-1 (SARS1) and SARS-CoV-2 (SARS2)-infected cells. Validating the CoV consensomes, we show that high confidence transcriptional targets (HCTs) of MERS, SARS1 and SARS2 infection intersect with HCTs of signaling pathway nodes with known roles in CoV infection. Among a series of novel use cases, we gather evidence for hypotheses that SARS2 infection efficiently represses E2F family HCTs encoding key drivers of DNA replication and the cell cycle; that progesterone receptor signaling antagonizes SARS2-induced inflammatory signaling in the airway epithelium; and that SARS2 HCTs are enriched for genes involved in epithelial to mesenchymal transition. The CoV infection consensomes and HCT intersection analyses are freely accessible through the Signaling Pathways Project knowledgebase, and as Cytoscape-style networks in the Network Data Exchange repository.
摘要：
围绕冠状病毒（CoV）感染和人类细胞信号传导途径之间的转录界面建立共识可以催化新型抗CoV疗法的开发。这里,我们使用公开存档的转录组数据集来计算共识监管签名，或consensomes，根据人类基因在MERS-CoV（MERS）中的差异表达率对其进行排名，SARS-CoV-1(SARS1)和SARS-CoV-2(SARS2)感染的细胞。验证CoV传感器，我们证明了MERS的高置信度转录靶标(HCTs)，SARS1和SARS2感染与在CoV感染中具有已知作用的信号通路节点的HCTs相交。在一系列新颖的用例中，我们收集了以下假设的证据:SARS2感染可有效抑制编码DNA复制和细胞周期关键驱动因素的E2F家族HCTs;孕激素受体信号可拮抗SARS2诱导的气道上皮炎症信号;SARS2HCTs富含参与上皮向间充质转化的基因.通过信号通路项目知识库可以自由访问CoV感染的上下文和HCT交叉分析，并作为网络数据交换存储库中的Cytoscape样式的网络。
