Gene expression network analysis provides potential targets against SARS-CoV-2.
Sci Rep, 2020/12/14;10(1):21863.
Hernández Cordero AI[1], Li X[2], Yang CX[2], Milne S[2, 3, 4], Bossé Y[5], Joubert P[5], Timens W[6], van den Berge M[7], Nickle D[8], Hao K[9], Sin DD[2, 3]
Affiliations
PMID: 33318519DOI: 10.1038/s41598-020-78818-w
Impact factor: 4.996
Abstract
Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets. Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions. ACE2 was in a module of 681 co-expressed genes; 10 genes with moderate-high correlation with ACE2 (r > 0.3, FDR < 0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 31 of these genes were enriched in the gene ontology biologic process 'receptor-mediated endocytosis', and 52 TMPRSS2-correlated genes had known interactions with drug compounds. Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may accelerate the development of COVID-19 therapeutics.
MeSH terms
Adult; Aged; Angiotensin-Converting Enzyme 2; COVID-19; Cohort Studies; Databases, Chemical; Female; Humans; Lung; Male; Middle Aged; Receptors, Coronavirus; Serine Endopeptidases; Transcriptome
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