Consistent and correctable bias in metagenomic sequencing experiments

• DOI: 10.7554/elife.46923
• Publication Date: 2019-09-10T00:00:22Z
• Authors: Michael R McLaren; Amy D Willis; Benjamin J Callahan
• Keywords: Spurious relationship

Marker-gene and metagenomic sequencing have profoundly expanded our ability to measure biological communities. But the measurements they provide differ from truth, often dramatically, because these experiments are biased toward detecting some taxa over others. This experimental bias makes taxon or gene abundances measured by different protocols quantitatively incomparable can lead spurious conclusions. We propose a mathematical model for how distorts community based on properties of real experiments. validate this with 16S rRNA shotgun metagenomics data defined bacterial Our better fits despite being simpler than previous models. illustrate be used evaluate protocols, understand effect downstream statistical analyses, correct given suitable calibration controls. These results illuminate new avenues truly quantitative reproducible measurements.