Large-scale validation of miRNAs by disease association, evolutionary conservation and pathway activity
| Autor: | Rudi Balling, Nicole Ludwig, Hannah Schrörs, Valentina Galata, Eckart Meese, Ulrike Fischer, Robert Bals, Tim Kehl, Julia Alles, Hanno Huwer, Thomas Laufer, Hans-Peter Lenhof, Lars Geffers, Aneta Düsterloh, Rejko Krüger, Marie Minet, Fabian Kern, Christina Backes, Jochen Kohlhaas, Mustafa Kahramann, Tobias Fehlmann, Andreas Keller |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Microarray
Neurology [D14] [Human health sciences] Disease Association Computational biology Biology Scale validation DNA sequencing Cell Line Conserved sequence 03 medical and health sciences 0302 clinical medicine microRNA validation microRNA Humans Genetic Predisposition to Disease evolution of miRNAs Northern blot Molecular Biology Genetic Association Studies 030304 developmental biology 0303 health sciences Neurologie [D14] [Sciences de la santé humaine] Sequence Analysis RNA target pathways Computational Biology High-Throughput Nucleotide Sequencing Reproducibility of Results Cell Biology northern blot MicroRNAs Gene Expression Regulation NGS 030220 oncology & carcinogenesis RNA Interference Pathway activity microarray Research Paper |
| Zdroj: | RNA Biology. 16:93-103 |
| ISSN: | 1555-8584 1547-6286 |
| DOI: | 10.1080/15476286.2018.1559689 |
| Popis: | 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 ). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|