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|a Motivation: To complement experimental efforts, machine learning-based computational methods are playing an increasingly important role to predict human-virus protein-protein interactions (PPIs). Furthermore, transfer learning can effectively apply prior knowledge obtained from a large source dataset/task to a small target dataset/task, improving prediction performance. Results: To predict interactions between human and viral proteins, we combine evolutionary sequence profile features with a Siamese convolutional neural network (CNN) architecture and a multi-layer perceptron. Our architecture outperforms various feature encodings-based machine learning and state-of-the-art prediction methods. As our main contribution, we introduce two transfer learning methods (i.e. 'frozen' type and 'fine-tuning' type) that reliably predict interactions in a target human-virus domain based on training in a source human-virus domain, by retraining CNN layers. Finally, we utilize the 'frozen' type transfer learning approach to predict human-SARS-CoV-2 PPIs, indicating that our predictions are topologically and functionally similar to experimentally known interactions. © 2021 The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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