Large-scale validation of miRNAs by disease association, evolutionary conservation and pathway activity

Tobias Fehlmann, Thomas Laufer, Christina Backes, Mustafa Kahramann, Julia Alles, Ulrike Fischer, Marie Minet, Nicole Ludwig, Fabian Kern, Tim Kehl, Valentina Galata, Aneta Düsterloh, Hannah Schrörs, Jochen Kohlhaas, Robert Bals, Hanno Huwer, Lars Geffers, Rejko Krüger, Rudi Balling, Hans Peter LenhofEckart Meese, Andreas Keller*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

The validation of microRNAs (miRNAs) identified by next generation sequencing involves amplification-free and hybridization-based detection of transcripts as criteria for confirming valid miRNAs. Since respective validation is frequently not performed, miRNA repositories likely still contain a substantial fraction of false positive candidates while true miRNAs are not stored in the repositories yet. Especially if downstream analyses are performed with these candidates (e.g. target or pathway prediction), the results may be misleading. In the present study, we evaluated 558 mature miRNAs from miRBase and 1,709 miRNA candidates from next generation sequencing experiments by amplification-free hybridization and investigated their distributions in patients with various disease conditions. Notably, the most significant miRNAs in diseases are often not contained in the miRBase. However, these candidates are evolutionary highly conserved. From the expression patterns, target gene and pathway analyses and evolutionary conservation analyses, we were able to shed light on the complexity of miRNAs in humans. Our data also highlight that a more thorough validation of miRNAs identified by next generation sequencing is required. The results are available in miRCarta (https://mircarta.cs.uni-saarland.de).

Original languageEnglish
Pages (from-to)93-103
Number of pages11
JournalRNA Biology
Volume16
Issue number1
DOIs
Publication statusPublished - 2 Jan 2019
Externally publishedYes

Keywords

  • MicroRNA validation
  • NGS
  • evolution of miRNAs
  • microarray
  • northern blot
  • target pathways

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