Prediction of mutation effects using a deep temporal convolutional network

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Motivation: Accurate prediction of the effects of genetic variation is a major goal in biological research. Towards this goal, numerous machine learning models have been developed to learn information from evolutionary sequence data. The most effective method so far is a deep generative model based on the variational autoencoder (VAE) that models the distributions using a latent variable. In this study, we propose a deep autoregressive generative model named mutationTCN, which employs dilated causal convolutions and attention mechanism for the modeling of inter-residue correlations in a biological sequence. Results: We show that this model is competitive with the VAE model when tested against a set of 42 high-throughput mutation scan experiments, with the mean improvement in Spearman rank correlation similar to 0.023. In particular, our model can more efficiently capture information from multiple sequence alignments with lower effective number of sequences, such as in viral sequence families, compared with the latent variable model. Also, we extend this architecture to a semi-supervised learning framework, which shows high prediction accuracy. We show that our model enables a direct optimization of the data likelihood and allows for a simple and stable training process.
Publisher
OXFORD UNIV PRESS
Issue Date
2020-04
Language
English
Article Type
Article
Citation

BIOINFORMATICS, v.36, no.7, pp.2047 - 2052

ISSN
1367-4803
DOI
10.1093/bioinformatics/btz873
URI
http://hdl.handle.net/10203/274778
Appears in Collection
BiS-Journal Papers(저널논문)
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