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. 2022 Dec 7;13(12):2304.
doi: 10.3390/genes13122304.

Ontological Analysis of Coronavirus Associated Human Genes at the COVID-19 Disease Portal

Shur-Jen Wang  1 , Kent C Brodie  2 , Jeffrey L De Pons  1 , Wendy M Demos  1 , Adam C Gibson  1 , G Thomas Hayman  1 , Morgan L Hill  1 , Mary L Kaldunski  1 , Logan Lamers  1 , Stanley J F Laulederkind  1 , Harika S Nalabolu  1 , Jyothi Thota  1 , Ketaki Thorat  1 , Marek A Tutaj  1 , Monika Tutaj  1 , Mahima Vedi  1 , Stacy Zacher  3 , Jennifer R Smith  1 , Melinda R Dwinell  4 , Anne E Kwitek  4
Affiliations

Ontological Analysis of Coronavirus Associated Human Genes at the COVID-19 Disease Portal

Shur-Jen Wang et al. Genes (Basel). .

Abstract

The COVID-19 pandemic stemmed a parallel upsurge in the scientific literature about SARS-CoV-2 infection and its health burden. The Rat Genome Database (RGD) created a COVID-19 Disease Portal to leverage information from the scientific literature. In the COVID-19 Portal, gene-disease associations are established by manual curation of PubMed literature. The portal contains data for nine ontologies related to COVID-19, an embedded enrichment analysis tool, as well as links to a toolkit. Using these information and tools, we performed analyses on the curated COVID-19 disease genes. As expected, Disease Ontology enrichment analysis showed that the COVID-19 gene set is highly enriched with coronavirus infectious disease and related diseases. However, other less related diseases were also highly enriched, such as liver and rheumatic diseases. Using the comparison heatmap tool, we found nearly 60 percent of the COVID-19 genes were associated with nervous system disease and 40 percent were associated with gastrointestinal disease. Our analysis confirms the role of the immune system in COVID-19 pathogenesis as shown by substantial enrichment of immune system related Gene Ontology terms. The information in RGD's COVID-19 disease portal can generate new hypotheses to potentiate novel therapies and prevention of acute and long-term complications of COVID-19.

Keywords: COVID-19; biological knowledgebase; database; disease enrichment; gene set enrichment; liver disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The COVID-19 Disease Portal landing page. (A). Annotations made to COVID-19 genes are organized into nine categories displayed in the COVID-19 Disease Portal. (B). The customized disease ontology browser showing terms associated with COVID-19 disease genes is shown at the middle. (C). Seven ontology enrichment analyses allow users to send COVID-19 disease genes to the MOET tool for gene set enrichment analysis.
Figure 2
Figure 2
The coronavirus disease gene distribution among the parent term (Coronavirus infectious disease) and its three child terms: COVID-19, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). The numbers in each area represent the gene count of that section and the percentage to all the coronavirus infectious disease genes. There are 1257 genes associated with COVID-19, 19 genes associated with MERS and 90 genes with SARS, totaling 1338 coronavirus infectious disease genes on display.
Figure 3
Figure 3
The disease term Comparison Heat Map visualized in the Gene Annotator tool. (A). COVID disease genes were visualized by their association with high level disease terms. (B). COVID genes associated with developmental disease were expanded to show their association with more granular terms under the branch. (C). COVID genes associated with disease of anatomical entity were expanded to show their association with more granular terms under the branch.
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