Protein Ubiquitylation and Sumoylation Site Prediction Based on Ensemble and Transfer Learning

Ubiquitylation, a typical post-translational modification (PTM), plays an important role in signal transduction, apoptosis and cell proliferation. A ubiquitylation like PTM, sumoylation also may affect gene mapping, expression and genomic replication. Over the past two decades, machine learning has been widely employed in protein ubiquitylation and sumoylation site prediction tools. These existing tools require feature engineering, but failed to provide general interpretable features and probably underutilized the growing amount of data. This prompted us to propose a deep learning-based model that integrates multiple convolution and fully-connected layers of seven supervised learning sub-models to extract deep representations from protein sequences and physico-chemical properties (PCPs). Especially, we divided PCPs into 6 clusters and customized deep networks accordingly for handling the high correlations among one cluster. A stacking ensemble strategy was applied to combine these deep representations to make prediction. Furthermore, with the advantage of transfer learning, our deep learning model can work well on protein sumoylation site prediction as well after fine-tuning. On the high-quality annotated database Swiss-Prot, our model outperformed several well-known ubiquitylation and sumoylation site prediction tools. Our code is freely available at https://github.com/ruiwcoding/DeepUbiSumoPre.