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

Authors :
Ellen C. Carbo
Igor A. Sidorov
Anneloes L. van Rijn-Klink
Nikos Pappas
Sander van Boheemen
Hailiang Mei
Pieter S. Hiemstra
Tomas M. Eagan
Eric C. J. Claas
Aloys C. M. Kroes
Jutte J. C. de Vries
Source :
Pathogens, Vol 11, Iss 3, p 340 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
20760817
Volume :
11
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Pathogens
Publication Type :
Academic Journal
Accession number :
edsdoj.b52b5dade8134dc694803a2547583e0d
Document Type :
article
Full Text :
https://doi.org/10.3390/pathogens11030340