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

Large-scale validation of miRNAs by disease association, evolutionary conservation and pathway activity. Fehlmann, T., Laufer, T., Backes, C., Kahramann, M., Alles, J., Fischer, U., Minet, M., Ludwig, N., Kern, F., Kehl, T., Galata, V., Düsterloh, A., Schrörs, H., Kohlhaas, J., Bals, R., Huwer, H., Geffers, L., Krüger, R., Balling, R., Lenhof, H., Meese, E., & Keller, A. RNA biology, 16:93-103, Taylor & Francis, January, 2019.
doi abstract bibtex

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).

@Article{Fehlmann2019,
  author       = {Tobias Fehlmann and Thomas Laufer and Christina Backes and Mustafa Kahramann and Julia Alles and Ulrike Fischer and Marie Minet and Nicole Ludwig and Fabian Kern and Tim Kehl and Valentina Galata and Aneta Düsterloh and Hannah Schrörs and Jochen Kohlhaas and Robert Bals and Hanno Huwer and Lars Geffers and Rejko Krüger and Rudi Balling and Hans-Peter Lenhof and Eckart Meese and Andreas Keller},
  title        = {Large-scale validation of miRNAs by disease association, evolutionary conservation and pathway activity},
  journal      = {RNA biology},
  publisher    = {Taylor & Francis},
  year         = {2019},
  volume       = {16},
  issue        = {1},
  pages        = {93-103},
  issn         = {93-103},
  issn-linking = {93-103},
  month        = jan,
  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).},
  doi          = {10.1080/15476286.2018.1559689},
  pii          = {10.1080/15476286.2018.1559689},
}

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