MSTL-Kace: Prediction of Prokaryotic Lysine Acetylation Sites Based on Multistage Transfer Learning Strategy.

As one of the most important post-translational modifications (PTM), lysine acetylation (Kace) plays an important role in various biological activities. Traditional experimental methods for identifying Kace sites are inefficient and expensive. Instead, several machine learning methods have been developed for Kace site prediction, and hand-crafted features have been used to encode the protein sequences. However, there are still two challenges: the complex biological information may be under-represented by these manmade features and the small sample issue of some species needs to be addressed. We propose a novel model, MSTL-Kace, which was developed based on transfer learning strategy with pretrained bidirectional encoder representations from transformers (BERT) model. In this model, the high-level embeddings were extracted from species-specific BERT models, and a two-stage fine-tuning strategy was used to deal with small sample issue. Specifically, a domain-specific BERT model was pretrained using all of the sequences in our data sets, which was then fine-tuned, or two-stage fine-tuned based on the training data set of each species to obtain the species-specific BERT models. Afterward, the embeddings of residues were extracted from the fine-tuned model and fed to the different downstream learning algorithms. After comparison, the best model for the six prokaryotic species was built by using a random forest. The results for the independent test sets show that our model outperforms the state-of-the-art methods on all six species. The source codes and data for MSTL-Kace are available at https://github.com/leo97king/MSTL-Kace.