WITMSG: Large-scale Prediction of Human Intronic m⁶A RNA Methylation Sites from Sequence and Genomic Features

Introduction: N ⁶-methyladenosine (m⁶A) is one of the most widely studied epigenetic modifications. It plays important roles in various biological processes, such as splicing, RNA localization and degradation, many of which are related to the functions of introns. Although a number of computational approaches have been proposed to predict the m⁶A sites in different species, none of them were optimized for intronic m⁶A sites. As existing experimental data overwhelmingly relied on polyA selection in sample preparation and the intronic RNAs are usually underrepresented in the captured RNA library, the accuracy of general m⁶A sites prediction approaches is limited for intronic m⁶A sites prediction task.

Methodology: A computational framework, WITMSG, dedicated to the large-scale prediction of intronic m⁶A RNA methylation sites in humans has been proposed here for the first time. Based on the random forest algorithm and using only known intronic m⁶A sites as the training data, WITMSG takes advantage of both conventional sequence features and a variety of genomic characteristics for improved prediction performance of intron-specific m⁶A sites.

Results and conclusion: It has been observed that WITMSG outperformed competing approaches (trained with all the m⁶A sites or intronic m⁶A sites only) in 10-fold cross-validation (AUC: 0.940) and when tested on independent datasets (AUC: 0.946). WITMSG was also applied intronome-wide in humans to predict all possible intronic m⁶A sites, and the prediction results are freely accessible at http://rnamd.com/intron/.