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

Abstract

The COVID-19 pandemic demands assimilation of all available biomedical knowledge to decode its mechanisms of pathogenicity and transmission. Despite the recent renaissance in unsupervised neural networks for decoding unstructured natural languages, a platform for the real-time synthesis of the exponentially growing biomedical literature and its comprehensive triangulation with deep omic insights is not available. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations extracted from unstructured biomedical text, and their triangulation with Single Cell RNA-sequencing based insights from over 25 tissues. Using this platform, we identify intersections between the pathologic manifestations of COVID-19 and the comprehensive expression profile of the SARS-CoV-2 receptor ACE2. We find that tongue keratinocytes, airway club cells, and ciliated cells are likely underappreciated targets of SARS-CoV-2 infection, in addition to type II pneumocytes and olfactory epithelial cells. We further identify mature small intestinal enterocytes as a possible hotspot of COVID-19 fecal-oral transmission, where an intriguing maturation-correlated transcriptional signature is shared between ACE2 and the other coronavirus receptors DPP4 (MERS-CoV) and ANPEP (ɑ-coronavirus). This study demonstrates how a holistic data science platform can leverage unprecedented quantities of structured and unstructured publicly available data to accelerate the generation of impactful biological insights and hypotheses.The nferX Platform Single-cell resource -https://academia.nferx.com/

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

“…Our cross-tissue analysis substantially expands on our 45, 46,58,112 and others' [113][114][115] earlier efforts, allowing us to identify cell subsets across diverse tissues that may be implicated in virus transmission, pathogenesis, or both. Focusing on pathogenesis, in addition to key subsets in the lung, airways and gut, we identified ACE2 + cells that co-express either TMPRSS2 or CTSL in diverse organs, many of which have been associated with severe disease.…”

COVID-19, Australia: Epidemiology Report 12: Reporting week ending 23:59 AEST 19 April 2020

“…17,18 This is supported by research finding a biological mechanism for the SARS-CoV-2 virus to cause olfactory dysfunction. 19,20 Examination of cases and their close contacts in China found a positive association between age and time from symptom onset to recovery. The study also found an association between clinical severity and time from symptom onset to time to recovery.…”

Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells

“…Recently, intestinal biopsies of SARS-CoV-2 infected patients clearly show the presence of replicating viruses in epithelial cells of the small and large intestine (Xiao et al, 2020). SARS-CoV-2 infection of the gastrointestinal tract is supported by the fact that ACE2, the virus receptor (Hoffmann et al, 2020), is expressed in intestinal epithelial cells (Zhao et al, 2020) (Lukassen et al, 2020) (Wu et al, 2020a) (Venkatakrishnan et al, 2020) and single cell sequencing analysis suggest that its expression is even higher on intestinal cells compared to lung cells (Xu et al, 2020a).This highlights that SARS-CoV-2 is not restricted to the lung but also infects the gastrointestinal tract. Importantly, many animal coronaviruses are well known to be enteric and are transmitted via the fecal-oral route (Wang and Zhang, 2016).…”