tetano
Editor, Senior Moderator
Sci Rep
. 2020 Dec 14;10(1):21863.
doi: 10.1038/s41598-020-78818-w.
Gene expression network analysis provides potential targets against SARS-CoV-2
Ana I Hern?ndez Cordero[SUP] 1 [/SUP], Xuan Li[SUP] 2 [/SUP], Chen Xi Yang[SUP] 2 [/SUP], Stephen Milne[SUP] 2 3 4 [/SUP], Yohan Boss?[SUP] 5 [/SUP], Philippe Joubert[SUP] 5 [/SUP], Wim Timens[SUP] 6 [/SUP], Maarten van den Berge[SUP] 7 [/SUP], David Nickle[SUP] 8 [/SUP], Ke Hao[SUP] 9 [/SUP], Don D Sin[SUP] 2 3 [/SUP]
Affiliations
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.
. 2020 Dec 14;10(1):21863.
doi: 10.1038/s41598-020-78818-w.
Gene expression network analysis provides potential targets against SARS-CoV-2
Ana I Hern?ndez Cordero[SUP] 1 [/SUP], Xuan Li[SUP] 2 [/SUP], Chen Xi Yang[SUP] 2 [/SUP], Stephen Milne[SUP] 2 3 4 [/SUP], Yohan Boss?[SUP] 5 [/SUP], Philippe Joubert[SUP] 5 [/SUP], Wim Timens[SUP] 6 [/SUP], Maarten van den Berge[SUP] 7 [/SUP], David Nickle[SUP] 8 [/SUP], Ke Hao[SUP] 9 [/SUP], Don D Sin[SUP] 2 3 [/SUP]
Affiliations
- PMID: 33318519
- DOI: 10.1038/s41598-020-78818-w
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.