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Implicating Gene and Cell Networks Responsible for Differential COVID-19 Host Responses via an Interactive Single Cell Web Portal

Kang Jin, Eric E. Bardes, Alexis Mitelpunkt, Jake Y. Wang, Surbhi Bhatnagar, Soma Sengupta, Daniel Pomeranz 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 Pomeranz 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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Summary

Numerous studies have provided single-cell transcriptome profiles of host responses to SARS-CoV-2 infection. Critically lacking however is a datamine that allows users to compare and explore cell profiles to gain insights and develop new hypotheses. To accomplish this, we harmonized datasets from COVID-19 and other control condition blood, bronchoalveolar lavage, and tissue samples, and derived a compendium of gene signature modules per cell type, subtype, clinical condition, and compartment. We demonstrate approaches to probe these via a new interactive web portal (http://toppcell.cchmc.org/ COVID-19). 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; and (3) a multilineage cell activator network able to drive extrafollicular B maturation via an ensemble of genes strongly associated with risk for developing post-viral autoimmunity.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵9 Lead contact

  • This version improves the figure descriptions (legends) and also distinguishes more succinctly the description of the web resource itself versus how users can develop hypotheses through the use of the system versus the specifics of the three principle hypotheses that we develop as examples of using the system.

  • 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 16, 2021.
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Implicating Gene and Cell Networks Responsible for Differential COVID-19 Host Responses via an Interactive Single Cell Web Portal
Kang Jin, Eric E. Bardes, Alexis Mitelpunkt, Jake Y. Wang, Surbhi Bhatnagar, Soma Sengupta, Daniel Pomeranz 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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Implicating Gene and Cell Networks Responsible for Differential COVID-19 Host Responses via an Interactive Single Cell Web Portal
Kang Jin, Eric E. Bardes, Alexis Mitelpunkt, Jake Y. Wang, Surbhi Bhatnagar, Soma Sengupta, Daniel Pomeranz 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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