Background: Recent advances in simultaneous measurement of RNA and protein abundances at single-cell level provide a unique opportunity to predict protein abundance from scRNA-seq data using machine learning models. However, existing machine learning methods have not considered relationship among the proteins sufficiently. Results: We formulate this task in a multi-label prediction framework where multiple proteins are linked to each other at the single-cell level. Then, we propose a novel method for single-cell RNA to protein prediction named PIKE-R2P, which incorporates protein-protein interactions (PPI) and prior knowledge embedding into a graph neural network. Compared with existing methods, PIKE-R2P could significantly improve prediction performance in terms of smaller errors and higher correlations with the gold standard measurements. Conclusion: The superior performance of PIKE-R2P indicates that adding the prior knowledge of PPI to graph neural networks can be a powerful strategy for cross-modality prediction of protein abundances at the single-cell level.

Graph neural network; Knowledge embedding; Protein prediction; Single-cell