@article{16,
  keywords = {Humans, Computational Biology, DNA Virus Infections, DNA Viruses, High-Throughput Nucleotide Sequencing, Metagenomics, Molecular Diagnostic Techniques, Sensitivity and Specificity, Transplantation},
  author = {Meredith Carpenter and Susanna Tan and Thomas Watson and Rowena Bacher and Vaishnavi Nagesh and Alain Watts and Gordon Bentley and Jenna Weber and ChunHong Huang and Malaya Sahoo and Armin Hinterwirth and Thuy Doan and Theodore Carter and Queeny Dong and Stéphane Gourguechon and Eric Harness and Sean Kermes and Srihari Radhakrishnan and Gongbo Wang and Alejandro Quiroz-Zárate and Jesus Ching and Benjamin Pinsky},
  title = {Metagenomic Next-Generation Sequencing for Identification and Quantitation of Transplant-Related DNA Viruses.},
  abstract = {<p>Infections with DNA viruses are frequent causes of morbidity and mortality in transplant recipients. This study describes the analytical and clinical performance characteristics of the Arc Bio Galileo Pathogen Solution, an all-inclusive metagenomic next-generation sequencing (mNGS) reagent and bioinformatics pipeline that allows the simultaneous quantitation of 10 transplant-related double-stranded DNA (dsDNA) viruses (adenovirus [ADV], BK virus [BKV], cytomegalovirus [CMV], Epstein-Barr virus [EBV], human herpesvirus 6A [HHV-6A], HHV-6B, herpes simplex virus 1 [HSV-1], HSV-2, JC virus [JCV], and varicella-zoster virus [VZV]). The mNGS 95% limit of detection ranged from 14 copies/ml (HHV-6) to 191 copies/ml (BKV), and the lower limit of quantitation ranged from 442 international units (IU)/ml (EBV) to 661 copies/ml (VZV). An evaluation of 50 residual plasma samples with at least one DNA virus detected in prior clinical testing showed a total percent agreement of mNGS and quantitative PCR (qPCR) of 89.2% (306/343), with a κ statistic of 0.725. The positive percent agreement was 84.9% (73/86), and the negative percent agreement was 90.7% (233/257). Furthermore, mNGS detected seven subsequently confirmed coinfections that were not initially requested by qPCR. Passing-Bablok regression revealed a regression line of  = 0.953 + 0.075 (95% confidence interval [CI] of the slope, 0.883 to 1.011; intercept, -0.100 to 0.299), and Bland-Altman analysis (mNGS - qPCR) showed a slight positive bias (0.28 log concentration; 95% limits of agreement, -0.62 to 1.18). In conclusion, the mNGS-based Galileo pipeline demonstrates analytical and clinical performance comparable to that of qPCR for transplant-related DNA viruses.</p>
},
  year = {2019},
  journal = {J Clin Microbiol},
  volume = {57},
  month = {2019 12},
  issn = {1098-660X},
  doi = {10.1128/JCM.01113-19},
  language = {eng},
}