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A Web Portal and Workbench for Biological Dissection of Single Cell COVID-19 Host Responses

Kang Jin, Eric E. Bardes, Alexis Mitelpunkt, Jake Y. Wang, Surbhi Bhatnagar, Soma Sengupta, Daniel P. Krummel, Marc E. Rothenberg, Bruce J. Aronow
doi: https://doi.org/10.1101/2021.06.07.447287
Kang Jin
1Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA
2Department of Biomedical Informatics, University of Cincinnati, Cincinnati, OH, 45229, USA
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Eric E. Bardes
1Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA
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Alexis Mitelpunkt
1Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA
3Pediatric Rehabilitation, Dana-Dwek Children’s Hospital, Tel Aviv Medical Center, Tel Aviv, 6423906, Israel
4Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel
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Jake Y. Wang
1Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA
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Surbhi Bhatnagar
1Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA
5Department of Electrical Engineering and Computer Science, University of Cincinnati, Cincinnati, OH, 45221, USA
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Soma Sengupta
6Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA
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Daniel P. Krummel
6Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA
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Marc E. Rothenberg
7Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, 45229, USA
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Bruce J. Aronow
1Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA
8Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH, 45256, USA
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  • For correspondence: bruce.aronow@cchmc.org
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Abstract

Numerous studies have provided single-cell transcriptome profiles of host responses to SARS-CoV-2 infection. Critically lacking however is a reusable datamine to allow users to compare and explore these data for insight, inference, and hypothesis generation. To accomplish this, we harmonized datasets from blood, bronchoalveolar lavage and tissue samples from COVID-19 and other control conditions and derived a compendium of gene signature modules per cell type, subtype, clinical condition and compartment. We demonstrate approaches for exploring and evaluating their significance via a new interactive web portal (ToppCell). As examples, we develop three hypotheses: (1) a multicellular signaling cascade among alternatively differentiated monocyte-derived macrophages whose tasks include T cell recruitment and activation; (2) novel platelet subtypes with drastically modulated expression of genes responsible for adhesion, coagulation and thrombosis; (3) a multilineage cell activator network able to drive extrafollicular B maturation via an ensemble of genes extensively associated with risk for developing autoimmunity.

Teaser Implicating COVID-19 Gene and Cell Networks Responsible for Inflammation, Thromboembolism and Autoimmune Pathobiology.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://toppcell.cchmc.org/biosystems/go/index3/COVID-19%20Atlas

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 07, 2021.
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A Web Portal and Workbench for Biological Dissection of Single Cell COVID-19 Host Responses
Kang Jin, Eric E. Bardes, Alexis Mitelpunkt, Jake Y. Wang, Surbhi Bhatnagar, Soma Sengupta, Daniel P. Krummel, Marc E. Rothenberg, Bruce J. Aronow
bioRxiv 2021.06.07.447287; doi: https://doi.org/10.1101/2021.06.07.447287
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A Web Portal and Workbench for Biological Dissection of Single Cell COVID-19 Host Responses
Kang Jin, Eric E. Bardes, Alexis Mitelpunkt, Jake Y. Wang, Surbhi Bhatnagar, Soma Sengupta, Daniel P. Krummel, Marc E. Rothenberg, Bruce J. Aronow
bioRxiv 2021.06.07.447287; doi: https://doi.org/10.1101/2021.06.07.447287

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