miRbiom: Machine-Learning on Bayesian Causal Nets of RBP-miRNA interactions successfully predicts miRNA profiles

Abstract

Formation of mature miRNAs and their expression is a highly controlled process. It is very much dependent upon the post-transcriptional regulatory events. Recent findings suggest that several RNA binding proteins beyond Drosha/Dicer are involved in the processing of miRNAs. Deciphering of conditional networks for these RBP-miRNA interactions may help to reason the spatio-temporal nature of miRNAs which can also be used to predict miRNA profiles. In this direction, >25TB of data from different platforms were studied (CLIP-seq/ RNA-seq/miRNA-seq) to develop Bayesian causal networks capable of reasoning miRNA biogenesis. The networks ably explained the miRNA formation when tested across a large number of conditions and experimentally validated data. The networks were modeled into an XGBoost machine learning system where expression information of the network compo- nents was found capable to quantitatively explain the miRNAs formation levels and their pro- files. The models were developed for 1,204 human miRNAs whose accurate expression level could be detected directly from the RNA-seq data alone without any need of doing sep- arate miRNA profiling experiments like miRNA-seq or arrays. A first of its kind, miRbiom per- formed consistently well with high average accuracy (91%) when tested across a large number of experimentally established data from several conditions. It has been imple- mented as an interactive open access web-server where besides finding the profiles of miR- NAs, their downstream functional analysis can also be done. miRbiom will help to get an accurate prediction of human miRNAs profiles in the absence of profiling experiments and will be an asset for regulatory research areas. The study also shows the importance of hav- ing RBP interaction information in better understanding the miRNAs and their functional pro- jectiles where it also lays the foundation of such studies and software in future.