The two-stage molecular scenery of SARS-CoV-2 infection with implications to disease severity: An in-silico quest

• DOI: 10.3389/fimmu.2023.1251067
• Publication Date: 2023-11-22T14:59:24Z
• Authors: George Potamias; Polymnia Gkoublia; Alexandros Kanter...
• Keywords: SARS-CoV-2; Immunology; Patient Acuity; COVID-19; Cell Differentiation; RC581-607; diagnostic and prognostic classifier models; pathway enrichment analysis; 3. Good health; machine learning; differential expression analysis; Interferon Type I; Humans; Immunologic diseases. Allergy

Introduction The two-stage molecular profile of the progression SARS-CoV-2 (SCOV2) infection is explored in terms five key biological/clinical questions: (a) does SCOV2 exhibits a profile? (b) SARS-CoV-1 (SCOV1) vs. SCOV2: do they differ? (c) and how differs from Influenza/INFL infection? (d) low viral-load (e) COVID-19 early host response relate to We provide positive answers above questions by analyzing time-series gene-expression profiles preserved cell-lines infected with SCOV1/2 or, individuals different viral-loads levels host-response phenotypes. Methods Our analytical methodology follows an in-silico quest organized around elaborate multi-step analysis pipeline including: utilization fifteen datasets NCBI’s gene expression omnibus/GEO repository; thorough designation INFL stages phenotypes; identification differentially expressed genes (DEGs) enriched biological processes pathways that contrast differentiate between employment graph-based clustering process for induction coherent groups networked as representative core fingerprints characterize In addition, relying on sensibly selected set induced fingerprint following Machine Learning approach, we devised assessed performance classifier models differentiation acute respiratory illness/ARI caused or other infections (diagnostic classifiers), well prediction disease severity (prognostic quite encouraging results. Results central finding our experiments demonstrates down-regulation type-I interferon (IFN-1), (ISGs) fundamental innate immune defense during stages, inverse hold later ones. It highlighted upregulation these after may prove beneficial preventing subsequent uncontrolled hyperinflammatory potentially lethal events. Discussion basic aim study was utilize intuitive, efficient productive way most relevant state-of-the-art bioinformatics methods reveal mechanisms which govern