Performance of Five Metagenomic Classifiers for Virus Pathogen Detection Using Respiratory Samples from a Clinical Cohort

Pathogens

Ellen C. Carbo¹  Aloys C. M. Kroes¹  Eric C. J. Claas¹  Sander van Boheemen¹  Anneloes L. van Rijn-Klink¹  Jutte J. C. de Vries¹  Igor A. Sidorov¹  Pieter S. Hiemstra²  Tomas M. Eagan³  Nikos Pappas⁴  Hailiang Mei⁴ 

[1] Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;Department of Pulmonology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;Department of Thoracic Medicine, Haukeland University Hospital, 5021 Bergen, Norway;Sequencing Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;

关键词: viral metagenomics;    bioinformatics;    pathogen detection;    next-generation sequencing;   

DOI  :  10.3390/pathogens11030340

来源: DOAJ

【 摘 要 】

Viral metagenomics is increasingly applied in clinical diagnostic settings for detection of pathogenic viruses. While several benchmarking studies have been published on the use of metagenomic classifiers for abundance and diversity profiling of bacterial populations, studies on the comparative performance of the classifiers for virus pathogen detection are scarce. In this study, metagenomic data sets (n = 88) from a clinical cohort of patients with respiratory complaints were used for comparison of the performance of five taxonomic classifiers: Centrifuge, Clark, Kaiju, Kraken2, and Genome Detective. A total of 1144 positive and negative PCR results for a total of 13 respiratory viruses were used as gold standard. Sensitivity and specificity of these classifiers ranged from 83 to 100% and 90 to 99%, respectively, and was dependent on the classification level and data pre-processing. Exclusion of human reads generally resulted in increased specificity. Normalization of read counts for genome length resulted in a minor effect on overall performance, however it negatively affected the detection of targets with read counts around detection level. Correlation of sequence read counts with PCR Ct-values varied per classifier, data pre-processing (R² range 15.1–63.4%), and per virus, with outliers up to 3 log₁₀ reads magnitude beyond the predicted read count for viruses with high sequence diversity. In this benchmarking study, sensitivity and specificity were within the ranges of use for diagnostic practice when the cut-off for defining a positive result was considered per classifier.

【 授权许可】

Unknown