I have performed DESeq2 on my data, and the results seem to differ from that of ANCOM very much. For example, in case of ANCOM, I found 3 features to be differentially abundant, while DESeq identified over a hundred! I was wondering why the results seem to be so drastically different?
DESeq2 makes some assumptions about biomass load that let it side-step compositionality. Those assumptions may be true for RNASeq data, but have been shown to be less valid for microbiome data in recent years, which can lead to a high false positive rate. ANCOM is quite conservative.
If you’re interested, you might check out some papers that have looked at this over the past few years: