Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

Wenjing Kang, Claus Heiner Bang-Berthelsen, Anja Holm, Anna J.S. Houben, Anne Holt Müller, Thomas Thymann, Flemming Pociot, Xavier P. Estivill, Marc R. Friedländer

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

miRNAs are small 22-nucleotide RNAs that can post-transcriptionally regulate gene expression. It has been proposed that dietary plant miRNAs can enter the human bloodstream and regulate host transcripts; however, these findings have been widely disputed. We here conduct the first comprehensive meta-study in the field, surveying the presence and abundances of cross-species miRNAs (xenomiRs) in 824 sequencing data sets from various human tissues and body fluids. We find that xenomiRs are commonly present in tissues (17%) and body fluids (69%); however, the abundances are low, comprising 0.001% of host human miRNA counts. Further, we do not detect a significant enrichment of xenomiRs in sequencing data originating from tissues and body fluids that are exposed to dietary intake (such as liver). Likewise, there is no significant depletion of xenomiRs in tissues and body fluids that are relatively separated from the main bloodstream (such as brain and cerebro-spinal fluids). Interestingly, the majority (81%) of body fluid xenomiRs stem from rodents, which are a rare human dietary contribution but common laboratory animals. Body fluid samples from the same studies tend to group together when clustered by xenomiR compositions, suggesting technical batch effects. Last, we performed carefully designed and controlled animal feeding studies, in which we detected no transfer of plant miRNAs into rat blood, or bovine milk sequences into piglet blood. In summary, our comprehensive computational and experimental results indicate that xenomiRs originate from technical artifacts rather than dietary intake.

Original languageEnglish
Pages (from-to)433-445
Number of pages13
JournalRNA
Volume23
Issue number4
DOIs
Publication statusPublished - 2017
Externally publishedYes

Fingerprint

Body Fluids
Human Body
Artifacts
MicroRNAs
Laboratory Animals
Cerebrospinal Fluid
Surveys and Questionnaires
Datasets
Rodentia
Milk
Nucleotides
RNA
Gene Expression
Liver
Brain

Keywords

  • Artifacts
  • Contamination
  • Exogenous miRNAs
  • Meta-study
  • MicroRNA
  • MiRNA
  • Next-generation sequencing

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Kang, W., Bang-Berthelsen, C. H., Holm, A., Houben, A. J. S., Müller, A. H., Thymann, T., ... Friedländer, M. R. (2017). Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts. RNA, 23(4), 433-445. https://doi.org/10.1261/rna.059725.116

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts. / Kang, Wenjing; Bang-Berthelsen, Claus Heiner; Holm, Anja; Houben, Anna J.S.; Müller, Anne Holt; Thymann, Thomas; Pociot, Flemming; Estivill, Xavier P.; Friedländer, Marc R.

In: RNA, Vol. 23, No. 4, 2017, p. 433-445.

Research output: Contribution to journalReview article

Kang, W, Bang-Berthelsen, CH, Holm, A, Houben, AJS, Müller, AH, Thymann, T, Pociot, F, Estivill, XP & Friedländer, MR 2017, 'Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts', RNA, vol. 23, no. 4, pp. 433-445. https://doi.org/10.1261/rna.059725.116
Kang W, Bang-Berthelsen CH, Holm A, Houben AJS, Müller AH, Thymann T et al. Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts. RNA. 2017;23(4):433-445. https://doi.org/10.1261/rna.059725.116
Kang, Wenjing ; Bang-Berthelsen, Claus Heiner ; Holm, Anja ; Houben, Anna J.S. ; Müller, Anne Holt ; Thymann, Thomas ; Pociot, Flemming ; Estivill, Xavier P. ; Friedländer, Marc R. / Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts. In: RNA. 2017 ; Vol. 23, No. 4. pp. 433-445.
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