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

Nicholas Parkinson, Natasha Rodgers, Max Head Fourman, Bo Wang, Marie Zechner, Maaike C Swets, Jonathan E Millar, Andy Law, Clark Russell, J. Kenneth Baillie, Sara Clohisey

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Received date: 24th September 2020

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 ranked genes 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 list of genes as a resource to inform and prioritise future studies.

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This is an abstract of a preprint hosted on a preprint server, which is currently undergoing peer review at Scientific Reports. The findings have yet to be thoroughly evaluated, nor has a decision on ultimate publication been made. Therefore, the results reported should not be considered conclusive, and these findings should not be used to inform clinical practice, or public health policy, or be promoted as verified information.

Scientific Reports

Nature Research, Springer Nature