An interactive single cell web portal identifies gene and cell networks in COVID-19 host responses
Kang Jin,
Eric E. Bardes,
Alexis Mitelpunkt,
Jake Y. Wang,
Surbhi Bhatnagar,
Soma Sengupta,
Daniel Pomeranz Krummel,
Marc E. Rothenberg,
Bruce J. Aronow
Affiliations
Kang Jin
Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Biomedical Informatics, University of Cincinnati, Cincinnati, OH 45229, USA
Eric E. Bardes
Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Alexis Mitelpunkt
Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Pediatric Rehabilitation, Dana-Dwek Children's Hospital, Tel Aviv Medical Center, Tel Aviv, 6423906, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel
Jake Y. Wang
Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Surbhi Bhatnagar
Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Electrical Engineering and Computer Science, University of Cincinnati, Cincinnati, OH 45221, USA
Soma Sengupta
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Daniel Pomeranz Krummel
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Marc E. Rothenberg
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
Bruce J. Aronow
Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Electrical Engineering and Computer Science, University of Cincinnati, Cincinnati, OH 45221, USA; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH 45256, USA; Corresponding author
Summary: Numerous studies have provided single-cell transcriptome profiles of host responses to SARS-CoV-2 infection. Critically lacking however is a data mine 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 interacting with, exploring, and functional evaluating these modules via a new interactive web portal ToppCell (http://toppcell.cchmc.org/). As examples, we develop three hypotheses: (1) alternatively-differentiated monocyte-derived macrophages form a multicelllar signaling cascade that drives T cell recruitment and activation; (2) COVID-19-generated platelet subtypes exhibit dramatically altered potential to adhere, coagulate, and thrombose; and (3) extrafollicular B maturation is driven by a multilineage cell activation network that expresses an ensemble of genes strongly associated with risk for developing post-viral autoimmunity.
