Transcriptogram analysis reveals relationship between viral titer and gene sets responses during Corona-virus infection

Abstract

To understand the difference between benign and severe outcomes after Coronavirus infection, we urgently need ways to clarify and quantify the time course of tissue and immune responses. Here we re-analyze 72-hour time-series microarrays generated in 2013 by Sims and collaborators for SARS-CoV-1 in vitro infection of a human lung epithelial cell line. Transcriptograms, a Bioinformatics tool to analyze genome-wide gene expression data, allow us to define an appropriate context-dependent threshold for mechanistic relevance of gene differential expression. Without knowing in advance which genes are relevant, classical analyses detect every gene with statistically-significant differential expression, leaving us with too many genes and hypotheses to be useful. Using a Transcriptogram-based top-down approach, we identified three major, differentially-expressed gene sets comprising 219 mainly immune-response-related genes. We identified timescales for alterations in mitochondrial activity, signaling and transcription regulation of the innate and adaptive immune systems and their relationship to viral titer. The methods can be applied to RNA data sets for SARS-CoV-2 to investigate the origin of differential responses in different tissue types, or due to immune or preexisting conditions or to compare cell culture, organoid culture, animal models and human-derived samples.

Bioinformatics-based investigation on the genetic influence between SARS-CoV-2 infections and idiopathic pulmonary fibrosis (IPF) diseases, and drug repurposing

“…To investigate the common pathogenetic processes of cHubGs, we selected top five common GO terms for each of BPs, MFs and CCs, and KEGG pathways that are significantly enriched by cHubGs in at least two of three databases (see Table 3). Among them, the association of the detected BPs (inflammatory response, response to virus, regulation of inflammatory response, response to tumor necrosis factor, response to cytokine) with COVID-19 and IPF diseases were supported by several independent studies [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74] . The SARS-CoV-2 infection is influenced by a severe inflammatory response with the release of a huge amount of cytokine storm known as pro-inflammatory cytokines.…”

Acetate-encapsulated Linolenic Acid Liposomes Reduce SARS-CoV-2 and RSV Infection

“…On the other hand, FFAR2 and FFAR4 have been shown to downregulate Th2 inflammatory pathways implicated in cytokine storm in severe COVID-19 cases, including inflammatory cytokines IL-1β and IL-6 [ 12 , 62 , 63 ]. These two FFARs are also known to be expressed in the lung epithelial cells and other immune cells [ 59 , 60 , 64 , 65 , 66 ]. To examine the basis of their antiviral roles in lung-derived Calu-3 cells, we used inhibitors of receptors that are known to bind to these free fatty acids [ 67 , 68 ].…”