Explainable Deep Learning for Augmentation of Small RNA Expression Profiles

Abstract

The lack of well-structured metadata annotations complicates the reusability and interpretation of the growing amount of publicly available RNA expression data. The machine learning-based prediction of metadata (data augmentation) can considerably improve the quality of expression data annotation. In this study, we systematically benchmark deep learning (DL) and random forest (RF)-based metadata augmentation of tissue, age, and sex using small RNA (sRNA) expression profiles. We use 4243 annotated sRNA-Seq samples from the sRNA expression atlas database to train and test the augmentation performance. In general, the DL machine learner outperforms the RF method in almost all tested cases. The average cross-validated prediction accuracy of the DL algorithm for tissues is 96.5%, for sex is 77%, and for age is 77.2%. The average tissue prediction accuracy for a completely new data set is 83.1% (DL) and 80.8% (RF). To understand which sRNAs influence DL predictions, we employ backpropagation-based feature importance scores using the DeepLIFT method, which enable us to obtain information on biological relevance of sRNAs.