Exact sequence variants should replace operational taxonomic units in marker-gene data analysis
Benjamin J. Callahana b✉, Paul J. McMurdiec d, Susan Holmese f
- aDepartment of Population Health and Pathobiology, NC State University , Raleigh NC, USA
- bDepartment of Population Health and Pathobiology, NC State University, Raleigh, NC, USA
- cWhole Biome Inc , San Francisco CA, USA
- dWhole Biome Inc, San Francisco, CA, USA
- eDepartment of Statistics, Stanford University , Stanford CA, USA
- fDepartment of Statistics, Stanford University, Stanford, CA, USA
- ✉Corresponding author
Papers open inside SciRah from the original publisher or repository; SciRah never hosts them.
Abstract
Recent advances have made it possible to analyze high-throughput marker-gene sequencing data without resorting to the customary construction of molecular operational taxonomic units (OTUs): clusters of sequencing reads that differ by less than a fixed dissimilarity threshold. New methods control errors sufficiently such that amplicon sequence variants (ASVs) can be resolved exactly, down to the level of single-nucleotide differences over the sequenced gene region. The benefits of finer resolution are immediately apparent, and arguments for ASV methods have focused on their improved resolution. Less obvious, but we believe more important, are the broad benefits that derive from the status of ASVs as consistent labels with intrinsic biological meaning identified independently from a reference database. Here we discuss how these features grant ASVs the combined advantages of closed-reference OTUs-including computational costs that scale linearly with study size, simple merging between independently processed data sets, and forward prediction-and of de novo OTUs-including accurate measurement of diversity and applicability to communities lacking deep coverage in reference databases. We argue that the improvements in reusability, reproducibility and comprehensiveness are sufficiently great that ASVs should replace OTUs as the standard unit of marker-gene analysis and reporting.
TL;DRIt is argued that the improvements in reusability, reproducibility and comprehensiveness are sufficiently great that ASVs should replace OTUs as the standard unit of marker-gene analysis and reporting. (Semantic Scholar)