A typical current computational meta'omic pipeline to analyze and contrast microbial communities. A typical current computational meta'omic pipeline to analyze and contrast microbial communities. After collecting microbiome samples, community DNA or RNA is extracted and sequenced, generating WMS samples (i.e., metagenomes) generally consisting of several million short reads each. This example uses 20 WMS samples from the oral cavity (10 from the buccal mucosa, and 10 from the tongue dorsum (The Human Microbiome Project Consortium, 2012b)). Complementary methods reconstruct the taxonomic characteristics (left) and metabolic potential (right) of the microbial communities. MetaPhlAn (Segata et al, 2012) is one of many alternatives to detect and quantify microbial clades with species‐level resolution (see Section 3), whereas HUMAnN (Abubucker et al, 2012) quantitatively characterizes genes, pathways, and metabolic modules from each community (see Section 4). Differentially abundant clades or pathways can then be identified and assessed by tools such as LEfSe (Segata et al, 2011) and represented graphically (e.g., here by GraPhlAn, http://huttenhower.sph.harvard.edu/graphlan). The step‐by‐step computational pipeline used to produce the analyses reported here is included as a tutorial in Supplementary Information and can also be downloaded from https://bitbucket.org/nsegata/metaphlan/wiki/MetaPhlAn_Pipelines_Tutorial. See Table I for alternative computational approaches to each of these currently common steps in meta'omic analysis. Nicola Segata et al. Mol Syst Biol 2013;9:666 © as stated in the article, figure or figure legend