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.