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Small amounts of misassembly can have disproportionate effects on pangenome-based metagenomic analyses
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Small amounts of misassembly can have disproportionate effects on pangenome-based metagenomic analyses
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Journal Article
Small amounts of misassembly can have disproportionate effects on pangenome-based metagenomic analyses
2025
Overview
Metagenome-assembled genomes, or MAGs, can be constructed without pure cultures of microbes. Large-scale efforts to build MAGs have yielded more complete pangenomes (i.e., sets of all genes found in one species). Pangenomes allow us to measure strain variation in gene content, which can strongly affect phenotype. However, because MAGs come from mixed communities, they can contaminate pangenomes with unrelated DNA; how much this impacts downstream analyses has not been studied. Using a metagenomic study of gut microbes in cirrhosis as our test case, we investigate how contamination affects analyses of microbial gene content. Surprisingly, even small, typical amounts of MAG contamination (<5%) result in disproportionately high levels of false positive associations (38%). Fortunately, we show that most contaminants can be automatically flagged and provide a simple method for doing so. Furthermore, applying this method reveals a new association between cirrhosis and gut microbial motility.
Publisher
American Society for Microbiology
Subject
