Using deep neural networks and biological subwords to detect protein S-sulfenylation sites

Protein S-sulfenylation is one kind of crucial post-translational modifications (PTMs) in which the hydroxyl group covalently binds to the thiol of cysteine. Some recent studies have shown that this modification plays an important role in signaling transduction, transcriptional regulation and apoptosis. To date, the dynamic of sulfenic acids in proteins remains unclear because of its fleeting nature. Identifying S-sulfenylation sites, therefore, could be the key to decipher its mysterious structures and functions, which are important in cell biology and diseases. However, due to the lack of effective methods, scientists in this field tend to be limited in merely a handful of some wet lab techniques that are time-consuming and not cost-effective. Thus, this motivated us to develop an in silico model for detecting S-sulfenylation sites only from protein sequence information. In this study, protein sequences served as natural language sentences comprising biological subwords. The deep neural network was consequentially employed to perform classification. The performance statistics within the independent dataset including sensitivity, specificity, accuracy, Matthews correlation coefficient and area under the curve rates achieved 85.71%, 69.47%, 77.09%, 0.5554 and 0.833, respectively. Our results suggested that the proposed method (fastSulf-DNN) achieved excellent performance in predicting S-sulfenylation sites compared to other well-known tools on a benchmark dataset.