Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks

Genome Res. 2015 Feb;25(2):257-67. doi: 10.1101/gr.178194.114. Epub 2014 Nov 5.

Abstract

We introduce a method for simultaneous prediction of microRNA-target interactions and their mediated competitive endogenous RNA (ceRNA) interactions. Using high-throughput validation assays in breast cancer cell lines, we show that our integrative approach significantly improves on microRNA-target prediction accuracy as assessed by both mRNA and protein level measurements. Our biochemical assays support nearly 500 microRNA-target interactions with evidence for regulation in breast cancer tumors. Moreover, these assays constitute the most extensive validation platform for computationally inferred networks of microRNA-target interactions in breast cancer tumors, providing a useful benchmark to ascertain future improvements.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Algorithms
  • Binding Sites
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cluster Analysis
  • Computational Biology / methods*
  • Epistasis, Genetic*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • RNA Interference*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*

Substances

  • 3' Untranslated Regions
  • Estrogen Receptor alpha
  • MicroRNAs
  • RNA, Messenger
  • estrogen receptor alpha, human