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串联共表达分析 SARS-CoV 病毒宿主因子与先前高通量筛选高度一致,并提出关键调控因子。

Serial co-expression analysis of host factors from SARS-CoV viruses highly converges with former high-throughput screenings and proposes key regulators.

机构信息

Centro Andaluz de Biologia del Desarrollo (CABD, UPO-CSIC-JA). Facultad de Ciencias Experimentales (Área de Genética), Universidad Pablo de Olavide, 41013, Sevilla, Spain.

Data Science & Big Data Lab, Universidad Pablo de Olavide, 41013, Sevilla, Spain.

出版信息

Brief Bioinform. 2021 Mar 22;22(2):1038-1052. doi: 10.1093/bib/bbaa419.

Abstract

The current genomics era is bringing an unprecedented growth in the amount of gene expression data, only comparable to the exponential growth of sequences in databases during the last decades. This data allow the design of secondary analyses that take advantage of this information to create new knowledge. One of these feasible analyses is the evaluation of the expression level for a gene through a series of different conditions or cell types. Based on this idea, we have developed Automatic and Serial Analysis of CO-expression, which performs expression profiles for a given gene along hundreds of heterogeneous and normalized transcriptomics experiments and discover other genes that show either a similar or an inverse behavior. It might help to discover co-regulated genes, and common transcriptional regulators in any biological model. The present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is an opportunity to test this novel approach due to the wealth of data that are being generated, which could be used for validating results. Thus, we have identified 35 host factors in the literature putatively involved in the infectious cycle of SARS-CoV viruses and searched for genes tightly co-expressed with them. We have found 1899 co-expressed genes whose assigned functions are strongly related to viral cycles. Moreover, this set of genes heavily overlaps with those identified by former laboratory high-throughput screenings (with P-value near 0). Our results reveal a series of common regulators, involved in immune and inflammatory responses that might be key virus targets to induce the coordinated expression of SARS-CoV-2 host factors.

摘要

当前的基因组学时代带来了基因表达数据数量的空前增长,仅这一数据量的增长就可与过去几十年中数据库中序列的指数级增长相媲美。这些数据允许设计利用这些信息的二次分析,以创造新的知识。其中一种可行的分析是通过一系列不同的条件或细胞类型来评估基因的表达水平。基于这一想法,我们开发了自动和连续共表达分析,该分析对数百个异构和标准化的转录组学实验中的给定基因进行表达谱分析,并发现具有相似或相反行为的其他基因。它有助于在任何生物学模型中发现共调控基因和共同的转录调控因子。目前的严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)大流行是测试这种新方法的机会,因为正在生成大量数据,这些数据可用于验证结果。因此,我们在文献中确定了 35 种宿主因子,推测它们参与了 SARS-CoV 病毒的感染周期,并搜索与它们紧密共表达的基因。我们发现了 1899 个共表达基因,其分配的功能与病毒周期密切相关。此外,这组基因与以前的实验室高通量筛选(接近 0 的 P 值)所鉴定的基因高度重叠。我们的结果揭示了一系列共同的调节剂,它们参与免疫和炎症反应,可能是诱导 SARS-CoV-2 宿主因子协调表达的关键病毒靶点。

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