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J Clin Med. 2021 Aug 13;10(16). doi: 10.3390/jcm10163567.

Weighted Gene Co-Expression Network Analysis Combined with Machine Learning Validation to Identify Key Modules and Hub Genes Associated with SARS-CoV-2 Infection.

Journal of clinical medicine

Hassan Karami, Afshin Derakhshani, Mohammad Ghasemigol, Mohammad Fereidouni, Ebrahim Miri-Moghaddam, Behzad Baradaran, Neda Jalili Tabrizi, Souzan Najafi, Antonio Giovanni Solimando, Leigh M Marsh, Nicola Silvestris, Simona De Summa, Angelo Virgilio Paradiso, Vito Racanelli, Hossein Safarpour

Affiliations

  1. Student Research Committee, Birjand University of Medical Sciences, Birjand 9717853577, Iran.
  2. Laboratory of Experimental Pharmacology, IRCCS-Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy.
  3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 516615731, Iran.
  4. Department of Computer Engineering, University of Birjand, Birjand 9717434765, Iran.
  5. Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand 9717853577, Iran.
  6. Cardiovascular Diseases Research Center & Department of Molecular Medicine, School of Medicine, Birjand University of Medical Sciences, Birjand 9717853577, Iran.
  7. Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz 516615731, Iran.
  8. Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", 70121 Bari, Italy.
  9. Ludwig Boltzmann Institute for Lung Vascular Research, Neue Stiftingtalstraße 6/VI, 8010 Graz, Austria.
  10. Medical Oncology Unit, IRCCS-Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy.
  11. Molecular Diagnostics and Pharmacogenetics Unit, IRCCS-Istituto Tumori 'Giovanni Paolo II', 70124 Bari, Italy.
  12. National Cancer Research Centre, Istituto Tumori G Paolo II, 70124 Bari, Italy.

PMID: 34441862 PMCID: PMC8397209 DOI: 10.3390/jcm10163567

Abstract

The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous loss of lives. Various clinical trials of vaccines and drugs are being conducted worldwide; nevertheless, as of today, no effective drug exists for COVID-19. The identification of key genes and pathways in this disease may lead to finding potential drug targets and biomarkers. Here, we applied weighted gene co-expression network analysis and LIME as an explainable artificial intelligence algorithm to comprehensively characterize transcriptional changes in bronchial epithelium cells (primary human lung epithelium (NHBE) and transformed lung alveolar (A549) cells) during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our study detected a network that significantly correlated to the pathogenicity of COVID-19 infection based on identified hub genes in each cell line separately. The novel hub gene signature that was detected in our study, including

Keywords: COVID-19; SARS-CoV-2; WGCNA; bronchial epithelium cells; explainable artificial intelligence; transcriptional profiling; treatment

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