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@ARTICLE{Wally:140475,
      author       = {Wally, N. and Schneider, M. and Thannesberger, J. and
                      Kastner, M. T. and Bakonyi, T. and Indik, S. and Rattei, T.
                      and Bedarf, J. and Hildebrand, F. and Law, J. and Jovel, J.
                      and Steininger, C.},
      title        = {{P}lasmid {DNA} contaminant in molecular reagents.},
      journal      = {Scientific reports},
      volume       = {9},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DZNE-2020-06797},
      pages        = {1652},
      year         = {2019},
      abstract     = {Background noise in metagenomic studies is often of high
                      importance and its removal requires extensive post-analytic,
                      bioinformatics filtering. This is relevant as significant
                      signals may be lost due to a low signal-to-noise ratio. The
                      presence of plasmid residues, that are frequently present in
                      reagents as contaminants, has not been investigated so far,
                      but may pose a substantial bias. Here we show that plasmid
                      sequences from different sources are omnipresent in
                      molecular biology reagents. Using a metagenomic approach, we
                      identified the presence of the (pol) of equine infectious
                      anemia virus in human samples and traced it back to the
                      expression plasmid used for generation of a commercial
                      reverse transcriptase. We found fragments of multiple other
                      expression plasmids in human samples as well as commercial
                      polymerase preparations. Plasmid contamination sources
                      included production chain of molecular biology reagents as
                      well as contamination of reagents from environment or human
                      handling of samples and reagents. Retrospective analyses of
                      published metagenomic studies revealed an inaccurate
                      signal-to-noise differentiation. Hence, the plasmid
                      sequences that seem to be omnipresent in molecular biology
                      reagents may misguide conclusions derived from
                      genomic/metagenomics datasets and thus also clinical
                      interpretations. Critical appraisal of metagenomic data sets
                      for the possibility of plasmid background noise is required
                      to identify reliable and significant signals.},
      keywords     = {Computational Biology / DNA Contamination / DNA, Viral:
                      analysis / DNA, Viral: genetics / Diagnostic Errors:
                      prevention $\&$ control / Genes, pol: genetics /
                      High-Throughput Nucleotide Sequencing / Humans / Indicators
                      and Reagents: analysis / Infectious Anemia Virus, Equine:
                      genetics / Metagenomics / Plasmids: analysis / Plasmids:
                      genetics / Retrospective Studies / Sequence Analysis, DNA:
                      methods},
      cin          = {AG Tamgüney 2},
      ddc          = {600},
      cid          = {I:(DE-2719)1013022},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30733546},
      pmc          = {pmc:PMC6367390},
      doi          = {10.1038/s41598-019-38733-1},
      url          = {https://pub.dzne.de/record/140475},
}