Computational Analysis of the Global Effects of Ly6E in the Immune Response to Coronavirus Infection Using Gene Networks

Abstract

Gene networks have arisen as a promising tool in the comprehensive modeling and analysis of complex diseases. Particularly in viral infections, the understanding of the host-pathogen mechanisms, and the immune response to these, is considered a major goal for the rational design of appropriate therapies. For this reason, the use of gene networks may well encourage therapy-associated research in the context of the coronavirus pandemic, orchestrating experimental scrutiny and reducing costs. In this work, gene co-expression networks were reconstructed from RNA-Seq expression data with the aim of analyzing the time-resolved effects of gene Ly6E in the immune response against the coronavirus responsible for murine hepatitis (MHV). Through the integration of differential expression analyses and reconstructed networks exploration, significant differences in the immune response to virus were observed in Ly6E Δ H S C compared to wild type animals. Results show that Ly6E ablation at hematopoietic stem cells (HSCs) leads to a progressive impaired immune response in both liver and spleen. Specifically, depletion of the normal leukocyte mediated immunity and chemokine signaling is observed in the liver of Ly6E Δ H S C mice. On the other hand, the immune response in the spleen, which seemed to be mediated by an intense chromatin activity in the normal situation, is replaced by ECM remodeling in Ly6E Δ H S C mice. These findings, which require further experimental characterization, could be extrapolated to other coronaviruses and motivate the efforts towards novel antiviral approaches.

A Tiny Viral Protein, SARS-CoV-2-ORF7b: Functional Molecular Mechanisms

“…In particular, its involvement in SNAREdriven vesicular transport, exocytic processes, and ERBB signaling has been identified but without a functional characterization that identifies the actual role of ORF7b in synergy with other viral proteins [152]. There are other studies that have endeavored to juxtapose the mechanisms of diseases between SARS1 and SARS2 [153,154], but none of them have deciphered any common molecular mechanism. Both viruses lead to acute respiratory distress, but many phenomenological observations show differences.…”

Computational Ensemble Gene Co-Expression Networks for the Analysis of Cancer Biomarkers

“…The aim of this section is to evaluate the GCNs generated both by our case study and by other co-expression network methods used in other works, WGCNA [57,58] and EnGNet [38,59].…”

Deciphering molecular mechanisms of SARS-CoV-2 pathogenesis and drug repurposing through GRN motifs: a comprehensive systems biology study

“…However, more information is available on the SARS-CoV molecular mechanism than SARS-CoV-2; there are still many gaps in our knowledge of the host response mechanisms to SARS-CoV. For example, although some studies have tried approximating both illnesses’ mechanisms (Delgado-Chaves et al 2020 ; Guzzi et al 2020 ), no study has yet deciphered the regulatory motif elements in SARS-CoV host response GRN. Although both diseases were soon known for their pathogenesis in leading to acute respiratory distress, a recent single-cell sequencing study predicted that SARS-CoV-2 could harm most other organs in the body, such as the heart, kidney, and brain (Zaim et al 2020 ).…”