The use of taxon-specific reference databases compromises metagenomic classification

Abstract

A recent article in BMC Genomics describes a new bioinformatics tool, HumanMycobiomeScan, to classify fungal taxa in metagenomic samples. This tool was used to characterize the gut mycobiome of hunter-gatherers and Western populations, resulting in the identification of a range of fungal species in the vast majority of samples. In the HumanMycobiomeScan pipeline, sequence reads are mapped against a reference database containing fungal genome sequences only. We argue that using reference databases comprised of a single taxonomic group leads to an unacceptably high number of false-positives due to: (i) mapping to conserved genetic regions in reference genomes, and (ii) sequence contamination i..