Knowledge synthesis from 100 million biomedical documents augments the deep expression profiling of coronavirus receptors

AJ Venkatakrishnan; Arjun Puranik; Akash Anand; David Zemmour; Xiang Yao; Xiaoying Wu; Ramakrishna Chilaka; Dariusz K Murakowski; Kristopher Standish; Bharathwaj Raghunathan; Tyler Wagner; Enrique Garcia-Rivera; Hugo Solomon; Abhinav Garg; Rakesh Barve; Anuli Anyanwu-Ofili; Najat Khan; Venky Soundararajan

We found that club cells (formerly known as Clara cells), were consistently among the highestexpressing respiratory cell types (Figures 3A-B) . Literature-derived local and global scores suggest that this ACE2-club cell connection is underappreciated, with a few documents discussing these concepts together (nferx link). We also found that ACE2 is detected in type II pneumocytes in multiple studies, although the percentage of expressing cells ranges from only 0.5-7% (Figures 3A-B) . This relatively low expression, which may be deemed inconsequential if viewed in isolation, is strongly supported by knowledge synthesis that highlights an existing association between ACE2 and type II pneumocytes (Figures 3A-B) . Indeed, multiple studies have demonstrated ACE2 expression in these cells [29] [30] [31] [32] [33] [34] [35] . Further, ACE2 expression in bulk RNAseq of GTEx lung samples (n = 578) is strongly correlated to markers of type II pneumocytes, with all seven surfactant protein-encoding genes among the top 4% of transcriptional correlations to ACE2 (out of the ~19,000 genes expressed at > 1 TPM in GTEx lung samples; hypergeometric p-value = 1.1x10 -10 ) ( Figure S20) .