Transcription factor activity after SARS-CoV-2 infection
To evaluate the effect of SARS-CoV-2 infection at the Transcription Factor (TF) level, we applied DoRothEA (Garcia-Alonso et al., 2019) to RNA-seq datasets of different human lung cell lines from a recent study (GSE147507) (Blanco-Melo et al., 2020). DoRothEA is a comprehensive resource containing a curated collection of TF-target interactions. Each TF-target interaction is associated with a confidence level based on the number of supporting evidence. Here we selected the most reliable interactions (A, B, and C levels) and computed TF activities based on the normalized expression of their targets using the VIPER algorithm (Alvarez et al., 2016). For the TF activity enrichment analysis, VIPER was executed with the Wald statistic resulting from the differential expression analysis at the gene level between controls and SARS-CoV-2 infected cells using the DESeq2 package (Love et al. 2014). In VIPER, we set the eset.filter parameter to FALSE and consider five as the minimum number of targets allowed per regulon.