Survey of 800+ datasets from human tissue and body fluid reveals XenomiRs are likely artifacts

Wenjing Kang, Claus Heiner Bang-Berthelsen, Anja Holm, Anna Houben, Anne Holt Muller, Thomas Thymann, Flemming Pociot, Xavier Estivill, Marc Riemer Friedländer

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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 datasets 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 rare human dietary contributions, 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
JournalR N A
Volume23
Pages (from-to)433-445
ISSN1355-8382
DOIs
Publication statusPublished - 2017

Keywords

  • Artifacts
  • Contamination
  • Meta-study
  • miRNA
  • Next generation sequencing

Cite this

Kang, W., Bang-Berthelsen, C. H., Holm, A., Houben, A., Muller, A. H., Thymann, T., ... Riemer Friedländer, M. (2017). Survey of 800+ datasets from human tissue and body fluid reveals XenomiRs are likely artifacts. R N A, 23, 433-445. https://doi.org/10.1261/rna.059725.116
Kang, Wenjing ; Bang-Berthelsen, Claus Heiner ; Holm, Anja ; Houben, Anna ; Muller, Anne Holt ; Thymann, Thomas ; Pociot, Flemming ; Estivill, Xavier ; Riemer Friedländer, Marc. / Survey of 800+ datasets from human tissue and body fluid reveals XenomiRs are likely artifacts. In: R N A. 2017 ; Vol. 23. pp. 433-445.
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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 datasets 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 rare human dietary contributions, 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.",
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author = "Wenjing Kang and Bang-Berthelsen, {Claus Heiner} and Anja Holm and Anna Houben and Muller, {Anne Holt} and Thomas Thymann and Flemming Pociot and Xavier Estivill and {Riemer Friedl{\"a}nder}, Marc",
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Kang, W, Bang-Berthelsen, CH, Holm, A, Houben, A, Muller, AH, Thymann, T, Pociot, F, Estivill, X & Riemer Friedländer, M 2017, 'Survey of 800+ datasets from human tissue and body fluid reveals XenomiRs are likely artifacts', R N A, vol. 23, pp. 433-445. https://doi.org/10.1261/rna.059725.116

Survey of 800+ datasets from human tissue and body fluid reveals XenomiRs are likely artifacts. / Kang, Wenjing; Bang-Berthelsen, Claus Heiner; Holm, Anja; Houben, Anna; Muller, Anne Holt; Thymann, Thomas; Pociot, Flemming; Estivill, Xavier; Riemer Friedländer, Marc.

In: R N A, Vol. 23, 2017, p. 433-445.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Survey of 800+ datasets from human tissue and body fluid reveals XenomiRs are likely artifacts

AU - Kang, Wenjing

AU - Bang-Berthelsen, Claus Heiner

AU - Holm, Anja

AU - Houben, Anna

AU - Muller, Anne Holt

AU - Thymann, Thomas

AU - Pociot, Flemming

AU - Estivill, Xavier

AU - Riemer Friedländer, Marc

PY - 2017

Y1 - 2017

N2 - 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 datasets 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 rare human dietary contributions, 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.

AB - 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 datasets 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 rare human dietary contributions, 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.

KW - Artifacts

KW - Contamination

KW - Meta-study

KW - miRNA

KW - Next generation sequencing

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DO - 10.1261/rna.059725.116

M3 - Journal article

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VL - 23

SP - 433

EP - 445

JO - R N A

JF - R N A

SN - 1355-8382

ER -