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Abstract
In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from the National Genomics Data Center repository, separating the genome of different virus strains from the Coronavirus family with 98.73% accuracy. The network’s behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are validated on samples from the National Center for Biotechnology Information and Global Initiative on Sharing All Influenza Data repositories, and are proven to be able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n = 6 previously tested positive), delivering a sensitivity similar to routine diagnostic methods, and 100% specificity. The proposed methodology has a substantial added value over existing methods, as it is able to both automatically identify promising primer sets for a virus from a limited amount of data, and deliver effective results in a minimal amount of time. Considering the possibility of future pandemics, these characteristics are invaluable to promptly create specific detection methods for diagnostics.
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1 Utrecht University, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234)
2 UMR 518 MIA-Paris, INRAE, Paris, France (GRID:grid.507621.7)
3 Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, México (GRID:grid.459608.6) (ISNI:0000 0001 0432 668X)
4 Erasmus Medical Center, Department of Viroscience, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X)
5 Universidad Central de Queretaro (UNICEQ), Departamento de Investigación, Santiago de Querétaro, Mexico (GRID:grid.5645.2)
6 Vrije Universiteit, Athena Institute, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227)
7 Utrecht University, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234); Danone Nutricia research, Department Immunology, Utrecht, The Netherlands (GRID:grid.468395.5) (ISNI:0000 0004 4675 6663)