PTransIPs: Identification of phosphorylation sites enhanced by protein PLM embeddings

TL;DR

PTransIPs is a novel deep learning framework that leverages protein PLM embeddings and Transformer architecture to accurately identify phosphorylation sites, outperforming existing methods and serving as a universal tool for peptide bioactivity prediction.

Contribution

It is the first to apply protein pre-trained language model embeddings to phosphorylation site prediction, enhancing performance and addressing dataset limitations.

Findings

Achieved AUCs of 0.9232 and 0.9660 for S/T and Y phosphorylation sites.

Outperforms existing state-of-the-art methods.

Serves as a universal framework for peptide bioactivity tasks.

Abstract

Phosphorylation is pivotal in numerous fundamental cellular processes and plays a significant role in the onset and progression of various diseases. The accurate identification of these phosphorylation sites is crucial for unraveling the molecular mechanisms within cells and during viral infections, potentially leading to the discovery of novel therapeutic targets. In this study, we develop PTransIPs, a new deep learning framework for the identification of phosphorylation sites. Independent testing results demonstrate that PTransIPs outperforms existing state-of-the-art (SOTA) methods, achieving AUCs of 0.9232 and 0.9660 for the identification of phosphorylated S/T and Y sites, respectively. PTransIPs contributes from three aspects. 1) PTransIPs is the first to apply protein pre-trained language model (PLM) embeddings to this task. It utilizes ProtTrans and EMBER2 to extract sequence and structure embeddings, respectively, as additional inputs into the model, effectively addressing issues of dataset size and overfitting, thus enhancing model performance; 2) PTransIPs is based on Transformer architecture, optimized through the integration of convolutional neural networks and TIM loss function, providing practical insights for model design and training; 3) The encoding of amino acids in PTransIPs enables it to serve as a universal framework for other peptide bioactivity tasks, with its excellent performance shown in extended experiments of this paper. Our code, data and models are publicly available at https://github.com/StatXzy7/PTransIPs.