PEPerMINT: Peptide Abundance Imputation in Mass Spectrometry-based Proteomics using Graph Neural Networks

Abstract

MotivationAccurate quantitative information about the protein abundance is crucial for understanding a biological system and its dynamics. Protein abundance is commonly estimated using label-free, bottom-up mass spectrometry protocols. Here, proteins are digested into peptides before quantification via mass spectrometry. However, missing peptide abundance values, which can make up more than 50% of all abundance values, are a common issue. They result in missing protein abundance values, which then hinder accurate and reliable downstream analyses. ResultsTo impute missing abundance values, we propose PEPerMINT, a graph neural network model working directly on the peptide level that flexibly takes both peptide-to-protein relationships in a graph format as well as amino acid sequence information into account. We benchmark our method against eleven common imputation methods on six diverse datasets, including cell lines, tissue, and plasma samples. We observe that PEPerMINT consistently outperforms other imputation methods. Its prediction performance remains high for varying degrees of missingness, different evaluation approaches and differential expression prediction. As an additional novel feature, PEPerMINT provides meaningful uncertainty estimates and allows for tailoring imputation to the users needs based on the reliability of imputed values. Availability and implementationThe code is available at https://github.com/DILiS-lab/pepermint.