Exploring the Knowledge of an Outstanding Protein to Protein Interaction Transformer.

Protein-to-protein interaction (PPI) prediction aims to predict whether two given proteins interact or not. Compared with traditional experimental methods of high cost and low efficiency, the current deep learning based approach makes it possible to discover massive potential PPIs from large-scale databases. However, deep PPI prediction models perform poorly on unseen species, as their proteins are not in the training set. Targetting on this issue, the paper first proposes PPITrans, a Transformer based PPI prediction model that exploits a language model pre-trained on proteins to conduct binary PPI prediction. To validate the effectiveness on unseen species, PPITrans is trained with Human PPIs and tested on PPIs of other species. Experimental results show that PPITrans significantly outperforms the previous state-of-the-art on various metrics, especially on PPIs of unseen species. For example, the AUPR improves 0.339 absolutely on Fly PPIs. Aiming to explore the knowledge learned by PPITrans from PPI data, this paper also designs a series of probes belonging to three categories. Their results reveal several interesting findings, like that although PPITrans cannot capture the spatial structure of proteins, it can obtain knowledge of PPI type and binding affinity, learning more than binary PPI.