Paying attention to the SARS-CoV-2 dialect : a deep neural network approach to predicting novel protein mutations.

Predicting novel mutations has long-lasting impacts on life science research. Traditionally, this problem is addressed through wet-lab experiments, which are often expensive and time consuming. The recent advancement in neural language models has provided stunning results in modeling and deciphering sequences. In this paper, we propose a Deep Novel Mutation Search (DNMS) method, using deep neural networks, to model protein sequence for mutation prediction. We use SARS-CoV-2 spike protein as the target and use a protein language model to predict novel mutations. Different from existing research which is often limited to mutating the reference sequence for prediction, we propose a parent-child mutation prediction paradigm where a parent sequence is modeled for mutation prediction. Because mutations introduce changing context to the underlying sequence, DNMS models three aspects of the protein sequences: semantic changes, grammatical changes, and attention changes, each modeling protein sequence aspects from shifting of semantics, grammar coherence, and amino-acid interactions in latent space. A ranking approach is proposed to combine all three aspects to capture mutations demonstrating evolving traits, in accordance with real-world SARS-CoV-2 spike protein sequence evolution. DNMS can be adopted for an early warning variant detection system, creating public health awareness of future SARS-CoV-2 mutations.