Microbiome research is rapidly expanding, which is why SeqBiome uses statistical methods from the front of the field. We provide advice on state-of-the-art experimental design procedures including technical and biological replicates, sample size, sequencing depth, and potential confounders. Our compositionally-robust analyses control for fundamental problems in microbiome data: differences in coverage, false correlation in abundance, and the prevalence of rare features. This gives us the strongest foundation to build on, whether using time series analysis, repeated-measure correlation between microbes, or differential proportionality in multi-omics data.