Prediction of Synaptically Localized RNAs in Human Neurons Using Developmental Brain Gene Expression Data

In the nervous system, synapses are special and pervasive structures between axonal and dendritic terminals, which facilitate electrical and chemical communications among neurons. Extensive studies have been conducted in mice and rats to explore the RNA pool at synapses and investigate RNA transport, local protein synthesis, and synaptic plasticity. However, owing to the experimental difficulties of studying human synaptic transcriptomes, the full pool of human synaptic RNAs remains largely unclear. We developed a new machine learning method, called PredSynRNA, to predict the synaptic localization of human RNAs. Training instances of dendritically localized RNAs were compiled from previous rodent studies, overcoming the shortage of empirical instances of human synaptic RNAs. Using RNA sequence and gene expression data as features, various models with different learning algorithms were constructed and evaluated. Strikingly, the models using the developmental brain gene expression features achieved superior performance for predicting synaptically localized RNAs. We examined the relevant expression features learned by PredSynRNA and used an independent test dataset to further validate the model performance. PredSynRNA models were then applied to the prediction and prioritization of candidate RNAs localized to human synapses, providing valuable targets for experimental investigations into neuronal mechanisms and brain disorders.