ToppMiR: ranking microRNAs and their mRNA targets based on biological functions and context

Nucleic Acids Res. 2014 Jul;42(Web Server issue):W107-13. doi: 10.1093/nar/gku409. Epub 2014 May 14.

Abstract

Identifying functionally significant microRNAs (miRs) and their correspondingly most important messenger RNA targets (mRNAs) in specific biological contexts is a critical task to improve our understanding of molecular mechanisms underlying organismal development, physiology and disease. However, current miR-mRNA target prediction platforms rank miR targets based on estimated strength of physical interactions and lack the ability to rank interactants as a function of their potential to impact a given biological system. To address this, we have developed ToppMiR (http://toppmir.cchmc.org), a web-based analytical workbench that allows miRs and mRNAs to be co-analyzed via biologically centered approaches in which gene function associated annotations are used to train a machine learning-based analysis engine. ToppMiR learns about biological contexts based on gene associated information from expression data or from a user-specified set of genes that relate to context-relevant knowledge or hypotheses. Within the biological framework established by the genes in the training set, its associated information content is then used to calculate a features association matrix composed of biological functions, protein interactions and other features. This scoring matrix is then used to jointly rank both the test/candidate miRs and mRNAs. Results of these analyses are provided as downloadable tables or network file formats usable in Cytoscape.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Internet
  • MicroRNAs / metabolism*
  • RNA, Messenger / metabolism*
  • Software*

Substances

  • MicroRNAs
  • RNA, Messenger