Bias in recent miRBase annotations potentially associated with RNA quality issues

Abstract Although microRNAs are supposed to be stable in-vivo, degradation processes potentially blur our knowledge on the small oligonucleotides. We set to quantify the effect of degradation on microRNAs in mouse to identify causes for distorted microRNAs patterns. In liver, we found 298, 99 and 8...

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Autores principales:	Nicole Ludwig, Meike Becker, Timo Schumann, Timo Speer, Tobias Fehlmann, Andreas Keller, Eckart Meese
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b5e7ede394c24184ad346b62cb222cde
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spelling	oai:doaj.org-article:b5e7ede394c24184ad346b62cb222cde2021-12-02T16:07:56ZBias in recent miRBase annotations potentially associated with RNA quality issues10.1038/s41598-017-05070-02045-2322https://doaj.org/article/b5e7ede394c24184ad346b62cb222cde2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05070-0https://doaj.org/toc/2045-2322Abstract Although microRNAs are supposed to be stable in-vivo, degradation processes potentially blur our knowledge on the small oligonucleotides. We set to quantify the effect of degradation on microRNAs in mouse to identify causes for distorted microRNAs patterns. In liver, we found 298, 99 and 8 microRNAs whose expression significantly correlated to RNA integrity, storage time at room temperature and storage time at 4 °C, respectively. Expression levels of 226 microRNAs significantly differed between liver samples with high RNA integrity compared to liver samples with low RNA integrity by more than two-fold. Especially the 157 microRNAs with increased expression in tissue samples with low RNA integrity were most recently added to miRBase. Testing potentially confounding sources, e.g. in-vitro degraded RNA depleted of small RNAs, we detected signals for 350 microRNAs, suggesting cross-hybridization of fragmented RNAs. Therefore, we conclude that especially microRNAs added in the latest miRBase versions might be artefacts due to RNA degradation. The results facilitate differentiation between degradation-resilient microRNAs, degradation-sensitive microRNAs, and likely erroneously annotated microRNAs. The latter were largely identified by NGS but not experimentally validated and can severely bias microRNA biomarker research and impact the value of microRNAs as diagnostic, prognostic or therapeutic tools.Nicole LudwigMeike BeckerTimo SchumannTimo SpeerTobias FehlmannAndreas KellerEckart MeeseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicole Ludwig Meike Becker Timo Schumann Timo Speer Tobias Fehlmann Andreas Keller Eckart Meese Bias in recent miRBase annotations potentially associated with RNA quality issues
description	Abstract Although microRNAs are supposed to be stable in-vivo, degradation processes potentially blur our knowledge on the small oligonucleotides. We set to quantify the effect of degradation on microRNAs in mouse to identify causes for distorted microRNAs patterns. In liver, we found 298, 99 and 8 microRNAs whose expression significantly correlated to RNA integrity, storage time at room temperature and storage time at 4 °C, respectively. Expression levels of 226 microRNAs significantly differed between liver samples with high RNA integrity compared to liver samples with low RNA integrity by more than two-fold. Especially the 157 microRNAs with increased expression in tissue samples with low RNA integrity were most recently added to miRBase. Testing potentially confounding sources, e.g. in-vitro degraded RNA depleted of small RNAs, we detected signals for 350 microRNAs, suggesting cross-hybridization of fragmented RNAs. Therefore, we conclude that especially microRNAs added in the latest miRBase versions might be artefacts due to RNA degradation. The results facilitate differentiation between degradation-resilient microRNAs, degradation-sensitive microRNAs, and likely erroneously annotated microRNAs. The latter were largely identified by NGS but not experimentally validated and can severely bias microRNA biomarker research and impact the value of microRNAs as diagnostic, prognostic or therapeutic tools.
format	article
author	Nicole Ludwig Meike Becker Timo Schumann Timo Speer Tobias Fehlmann Andreas Keller Eckart Meese
author_facet	Nicole Ludwig Meike Becker Timo Schumann Timo Speer Tobias Fehlmann Andreas Keller Eckart Meese
author_sort	Nicole Ludwig
title	Bias in recent miRBase annotations potentially associated with RNA quality issues
title_short	Bias in recent miRBase annotations potentially associated with RNA quality issues
title_full	Bias in recent miRBase annotations potentially associated with RNA quality issues
title_fullStr	Bias in recent miRBase annotations potentially associated with RNA quality issues
title_full_unstemmed	Bias in recent miRBase annotations potentially associated with RNA quality issues
title_sort	bias in recent mirbase annotations potentially associated with rna quality issues
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b5e7ede394c24184ad346b62cb222cde
work_keys_str_mv	AT nicoleludwig biasinrecentmirbaseannotationspotentiallyassociatedwithrnaqualityissues AT meikebecker biasinrecentmirbaseannotationspotentiallyassociatedwithrnaqualityissues AT timoschumann biasinrecentmirbaseannotationspotentiallyassociatedwithrnaqualityissues AT timospeer biasinrecentmirbaseannotationspotentiallyassociatedwithrnaqualityissues AT tobiasfehlmann biasinrecentmirbaseannotationspotentiallyassociatedwithrnaqualityissues AT andreaskeller biasinrecentmirbaseannotationspotentiallyassociatedwithrnaqualityissues AT eckartmeese biasinrecentmirbaseannotationspotentiallyassociatedwithrnaqualityissues
_version_	1718384680503345152

Bias in recent miRBase annotations potentially associated with RNA quality issues

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