A comprehensive evaluation of microbial differential abundance analysis methods: current status and potential solutions.

Based on the benchmarking study, we conclude that none of the existing DAA methods evaluated can be applied blindly to any real microbiome dataset. The applicability of an existing DAA method depends on specific settings, which are usually unknown a priori. To circumvent the difficulty of selecting the best DAA tool in practice, we design ZicoSeq, which addresses the major challenges in DAA and remedies the drawbacks of existing DAA methods. ZicoSeq can be applied to microbiome datasets from diverse settings and is a useful DAA tool for robust microbiome biomarker discovery. Video Abstract.