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The Coronavirus Network Explorer: mining a large-scale knowledge graph for effects of SARS-CoV-2 on host cell
Andreas Krämer1, Jean-Noël Billaud2, Stuart Tugendreich2
1Digital Insights, QIAGEN, Redwood City, USA. andreas.kramer@qiagen.com.
BMC Bioinformatics
|May 4, 2021
Summary
This study uses machine learning to map SARS-CoV-2 interactions with host genes, identifying potential drug targets for COVID-19 repurposing. The Coronavirus Network Explorer (CNE) visualizes these connections and validates existing drug trials.
Area of Science:
- Computational Biology
- Virology
- Pharmacology
Background:
- SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) interactions with host proteins are crucial for understanding viral pathogenesis.
- Existing network-based approaches for drug repurposing often lack explicit consideration of causal relationships (activation/inhibition).
Purpose of the Study:
- To develop and apply a machine learning approach to construct a knowledge graph connecting SARS-CoV-2 proteins to host functions, diseases, and pathways.
- To identify host genes as potential drug targets for COVID-19 by repurposing existing drugs.
- To explore how SARS-CoV-2 interferes with host cell functions.
Main Methods:
- Utilized a machine learning model based on gene embeddings derived from causal gene expression signatures.
- Constructed a large-scale knowledge graph from biomedical literature, incorporating directionality of effects (activation/inhibition).
- Developed the Coronavirus Network Explorer (CNE) for interactive visualization of 70 networks linking viral proteins to host biology.
Main Results:
- Generated 70 networks illustrating SARS-CoV-2 viral protein interactions with host functions, diseases, and pathways relevant to COVID-19.
- Found significant enrichment of existing drugs targeting network genes within those currently in clinical trials for COVID-19.
- The Coronavirus Network Explorer (CNE) provides interactive visualizations of experimental evidence.
Conclusions:
- The approach generates biologically plausible hypotheses for COVID-19 pathogenesis, linking to observed immunological, virological, and pathological aspects.
- Drug repurposing is guided by functional endpoints reflecting known viral biology and clinical observations, suggesting mechanisms of action.
- The CNE offers novel insights beyond conventional network methods and serves as a valuable tool for drug discovery and repurposing.
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