Broad Institute

Alina Chan, Ben Deverman of the Stanley Center for Psychiatric Research and Shing Hei Zhan (University of British Columbia) examined genomes from SARS-CoV-2 and SARS-CoV, the virus responsible for the 2003 SARS outbreak. They found that SARS-CoV-2 is genetically stable, similar to late epidemic SARS-CoV, and was already well adapted for human transmission when detected in late 2019. They analyze the genetic samples from the Wuhan seafood market and posit that these were likely from infected humans, not an intermediate host species.

Jason Nomburg, institute member Matthew Meyerson, and James DeCaprio (DFCI) conducted an in-depth analysis of existing SARS-CoV-2 genome datasets, and now describe new variations in SARS-CoV-2 RNA that may lead to variant viral proteins. Future studies will be necessary to understand how these mechanisms may influence SARS-CoV-2 pathogenesis.

To uncover the factors that regulate ACE2, the SARS-CoV-2 entry receptor, institute member Alex Shalek of the Klarman Cell Observatory, Jose Ordovas-Montanes, researchers from the Human Cell Atlas (HCA) Lung Biological Network, and other collaborators investigated large single-cell RNA-sequencing datasets from human, primate, and mouse tissues. They found that the gene encoding ACE2 is an interferon-stimulated gene in human upper airway epithelial cells,  but not in mice, raising key implications for disease models and pre-clinical therapeutic development. Learn more in Cell.

Researchers at the Broad’s Klarman Cell Observatory along with an international team of collaborators from across the Human Cell Atlas Lung Biological Network studied how the expression of SARS-CoV-2-associated genes – ACE2, TMPRSS2, and CTSL — in more than a million single human nasal, lung, and airway cells is related to age, sex, and smoking status. The researchers found increased expression of these genes with age and smoking status, suggesting a possible biological basis for the increased risk of severe COVID-19 infection seen in certain populations. Their analysis revealed that nasal, lung, and gut epithelial cells that express ACE2 and TMPRSS2, also express genes related to viral infection and immune function. 

Update, May 1, 2020: The authors have made all of the necessary data and code publicly available. Learn more in this Terra blog.

Corrie Painter, Nicole Persky, Kerstin Lindblad-Toh, Elinor Karlsson, and collaborators tapped the NCBI Protein database and other datasets to compare the structure of ACE2 (the SARS-CoV-2 receptor) in 410 vertebrate species, including 252 mammals. They identified 47 mammals that have a high or very high likelihood of being reservoirs or intermediate hosts for SARS-CoV-2.

The rapidly-growing COVID-19 Host Genetics Initiative is fostering collaboration around the globe to examine the genetics of coronavirus severity and susceptibility. Institute member Mark Daly, co-director of the Program in Medical and Population Genetics and director of the Institute for Molecular Medicine, Finland (FIMM), talks about the initiative's origins and what its members hope to achieve together.

The recent NIH-HCA 2020 Joint Meeting’s virtual session featured some of the latest COVID-19 single-cell studies, most of which are unpublished. Associate member Jay Rajagopal, institute member Alex Shalek, core institute member Aviv Regev, Regev lab graduate student Christoph Muus, and postdoctoral associate Chris Smillie – all from the Broad Institute’s Klarman Cell Observatory – along with collaborators from other institutions, presented their contributions towards international efforts of the Lung Cell Atlas Network to decipher the cell types likely infected by the virus. Learn more on the HCA COVID-19 resource page.