MicroRNAs are involved in almost all biological processes and have emerged as regulators of signaling pathways. Researchers from the German Research Center for Environmental Health show that miRNA target genes and pathway genes are not uniformly expressed across human tissues. To capture tissue specific effects, they developed a novel methodology for tissue specific pathway analysis of miRNAs. They incorporated the most recent and highest quality miRNA targeting data (TargetScan and StarBase), RNA-seq based gene expression data (EBI Expression Atlas) and multiple new pathway data sources to increase the biological relevance of the predicted miRNA-pathway associations.
The researchers identified new potential roles of miR-199a-3p, miR-199b-3p and the miR-200 family in hepatocellular carcinoma, involving the regulation of metastasis through MAPK and Wnt signaling. Also, an association of miR-571 and Notch signaling in liver fibrosis was proposed. To facilitate data update and future extensions of their tool, they developed a flexible database backend using the graph database neo4j. The new backend as well as the novel methodology were included in the updated miTALOS v2, a tool that provides insights into tissue specific miRNA regulation of biological pathways.
Database structure of miTALOS v2
(A) The miTALOS v2 dataset is stored in a graph database. The network structure allows for easy extension of the dataset. (B) The Cypher query language allows for simple queries on the network. With one query, the targets of a miRNA in a pathway can be accessed and filtered for tissue expression.
Availability – miTALOS v2 is available at http://mips.helmholtz-muenchen.de/mitalos.