miREM: an expectation-maximization approach for prioritizing miRNAs associated with gene-set

• Main Authors: Luqman Hakim Abdul Hadi, Quy Xiao Xuan Lin, Tri Tran Minh, Marie Loh, Hong Kiat Ng, Agus Salim, Richie Soong, Touati Benoukraf
• Format: Article
• Language: English
• Published: BMC 2018-08-01
• Series: BMC Bioinformatics
• Subjects: Gene regulation; miRNA; Expectation-maximization
• Online Access: http://link.springer.com/article/10.1186/s12859-018-2292-1

Abstract Background The knowledge of miRNAs regulating the expression of sets of mRNAs has led to novel insights into numerous and diverse cellular mechanisms. While a single miRNA may regulate many genes, one gene can be regulated by multiple miRNAs, presenting a complex relationship to model for accurate predictions. Results Here, we introduce miREM, a program that couples an expectation-maximization (EM) algorithm to the common approach of hypergeometric probability (HP), which improves the prediction and prioritization of miRNAs from gene-sets of interest. miREM has been made available through a web-server (https://bioinfo-csi.nus.edu.sg/mirem2/) that can be accessed through an intuitive graphical user interface. The program incorporates a large compendium of human/mouse miRNA-target prediction databases to enhance prediction. Users may upload their genes of interest in various formats as an input and select whether to consider non-conserved miRNAs, amongst filtering options. Results are reported in a rich graphical interface that allows users to: (i) prioritize predicted miRNAs through a scatterplot of HP p-values and EM scores; (ii) visualize the predicted miRNAs and corresponding genes through a heatmap; and (iii) identify and filter homologous or duplicated predictions by clustering them according to their seed sequences. Conclusion We tested miREM using RNAseq datasets from two single “spiked” knock-in miRNA experiments and two double knock-out miRNA experiments. miREM predicted these manipulated miRNAs as having high EM scores from the gene set signatures (i.e. top predictions for single knock-in and double knock-out miRNA experiments). Finally, we have demonstrated that miREM predictions are either similar or better than results provided by existing programs.