scPROTEIN: a versatile deep graph contrastive learning framework for single-cell proteomics embedding.

Single-cell proteomics sequencing technology sheds light on protein-protein interactions, posttranslational modifications and proteoform dynamics in the cell. However, the uncertainty estimation for peptide quantification, data missingness, batch effects and high noise hinder the analysis of single-cell proteomic data. It is important to solve this set of tangled problems together, but the existing methods tailored for single-cell transcriptomes cannot fully address this task. Here we propose a versatile framework designed for single-cell proteomics data analysis called scPROTEIN, which consists of peptide uncertainty estimation based on a multitask heteroscedastic regression model and cell embedding generation based on graph contrastive learning. scPROTEIN can estimate the uncertainty of peptide quantification, denoise protein data, remove batch effects and encode single-cell proteomic-specific embeddings in a unified framework. We demonstrate that scPROTEIN is efficient for cell clustering, batch correction, cell type annotation, clinical analysis and spatially resolved proteomic data exploration.