Evaluation of machine learning models on protein level inference from prioritized RNA features

The parallel measurement of transcriptome and proteome revealed unmatched profiles. Since proteomic analysis is more expensive and challenging than transcriptomic analysis, the question of how to use messenger RNA (mRNA) expression data to predict protein level is extremely important. Here, we comprehensively evaluated 13 machine learning models on inferring protein expression levels using RNA expression profile. A total of 20 proteogenomic datasets from three mainstream proteomic platforms with >2500 samples of 13 human tissues were collected for model evaluation. Our results highlighted that the appropriate feature selection methods combined with classical machine learning models could achieve excellent predictive performance. The voting ensemble model outperformed other candidate models across datasets. Adding the mRNA proxy model to the regression model further improved the prediction performance. The dataset and gene characteristics could affect the prediction performance. Finally, we applied the model to the brain transcriptome of cerebral cortex regions to infer the protein profile for better understanding the functional characteristics of the brain regions. This benchmarking work not only provides useful hints on the inherent correlation between transcriptome and proteome, but also has practical value of the transcriptome-based prediction of protein expression levels.