[HTML][HTML] Dynamic data-driven meta-analysis for prioritisation of host genes implicated in COVID-19

N Parkinson, N Rodgers, M Head Fourman, B Wang… - Scientific reports, 2020 - nature.com
N Parkinson, N Rodgers, M Head Fourman, B Wang, M Zechner, MC Swets, JE Millar, A Law
Scientific reports, 2020nature.com
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 …
Abstract
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.
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