PanomiR: A systems biology framework for analysis of multi-pathway targeting by miRNAs

Abstract

Charting miRNA regulation across multiple pathways is central to characterizing their role in disease. Yet, current methods expose only isolated miRNA-pathway interactions. We have developed a systems biology approach, Pathway networks of miRNA Regulation (PanomiR) that identifies miRNAs that coordinately target groups of pathways. PanomiR captures activity dynamics of pathways, detects dysregulated pathways, groups pathways by their co-expression, and detects miRNAs that specifically target these coordinated groups of dysregulated pathways. We have used PanomiR to explore disease-associated miRNAs and pathways in liver cancer. We show that it recapitulates known and novel liver cancer pathways, determines their up or down regulation, and sensitively captures biologically meaningful signals independent of detectable differential gene expression. PanomiR organizes liver cancer pathways into three broad groups that reflect pathogenic mechanisms of cancer: activation of transcription, cell cycle and proliferation, and dysregulated signalling. Using either experimentally-supported or predicted miRNA-mRNA interactions, PanomiR robustly detects and identifies miRNAs central to liver cancer, unbiased by the number of their gene targets-making it possible to place these cancer miRNAs using PanomiR into the context of co-activated pathways that they regulate. PanomiR is a sensitive, unbiased framework for detection of disease-specific multi-pathway programs under miRNA regulation. PanomiR is accessible as an open-source R/Bioconductor package: <https://bioconductor.org/packages/PanomiR>.

Converging peripheral blood microRNA profiles in Parkinson's disease and progressive supranuclear palsy

“…The statistical pathway analyses of the miRNA data for idiopathic Parkinson’s disease, progressive supranuclear palsy and controls were performed using the R statistical programming language (version 4.2.0, RRID:SCR_001905) and the PanomiR package for miRNA mapping and pathway activity profile generation (version 1.1.2). 48 First, Entrez/pathway mappings were retrieved from the MSigDB database (C2 collection of curated pathway gene sets), 34 and mappings between miRNAs and their target genes in Entrez format were obtained from the TargetScan database (RRID:SCR_010845). 49 Next, the FDR-adjusted significant miRNAs with P ≤ 0.05 for each pairwise comparison between conditions (idiopathic Parkinson’s disease versus controls, progressive supranuclear palsy versus idiopathic Parkinson’s disease and progressive supranuclear palsy versus controls) were used to determine their target genes.…”