The increasing body of literature describing the role of host factors in COVID-19 pathogenesis demonstrates the need to combine diverse, multi-omic data to evaluate and substantiate the most robust evidence and inform development of therapies. Here we present a dynamic ranking of host genes implicated in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). We conducted an extensive systematic review of experiments identifying potential host factors. Gene lists from diverse sources were integrated using Meta-Analysis by Information Content (MAIC). This previously described algorithm uses data-driven gene list weightings to produce a comprehensive ranked list of implicated host genes. From 32 datasets, the top ranked gene was PPIA, encoding cyclophilin A, a druggable target using cyclosporine. Other highly-ranked genes included proposed prognostic factors ( CXCL10 , CD4 , CD3E ) and investigational therapeutic targets ( IL1A ) for COVID-19. Gene rankings also inform the interpretation of COVID-19 GWAS results, implicating FYCO1 over other nearby genes in a disease-associated locus on chromosome 3. Researchers can search and review the gene rankings and the contribution of different experimental methods to gene rank at https://baillielab.net/maic/covid19 . As new data are published we will regularly update the list of genes as a resource to inform and prioritise future studies.
【저자키워드】 immunology, SARS-CoV-2, viral infection, Infectious diseases, Immunogenetics, 【초록키워드】 COVID-19, Meta-analysis, SARS-CoV, CXCL10, Infection, systematic review, MERS, CD4, MERS-CoV, Betacoronavirus, COVID-19 pathogenesis, Algorithm, Interpretation, Factors, Prognostic factors, GWAS, experiment, seasonal coronaviruses, resource, Other, Therapies, Evidence, therapeutic target, Prognostic factor, chromosome 3, cyclosporine, Factor, locus, chromosome, list, host genes, content, PPIA, datasets, IL1A, CD3E, FYCO1, Host, Weighting, data-driven, human betacoronavirus, robust, described, evaluate, conducted, implicated, host gene, disease-associated, list of gene, 【제목키워드】 COVID-19, dynamic, data-driven, implicated, host gene,