In 2014 Nature Biotechnology featured the metagenomic species (MGS) concept as high-resolution microbiomics, since then the method has been refined and sequencing technologies have improved allowing accurate profiling at subspecies level, this is ultra-high resolution microbiomics.
Ultra-high resolution microbiomics distinguish between microbial populations from individual subjects (strains) and describe these strains at the nucleotide level. This level of resolution challenges current comparative microbiomics analysis because the biological entities are unique to the subject. To overcome this, we employ statistical strategies that rely on phylogenetic distances between sample-specific strains to find associations that links subspecies clades to host phenotypes etc. These associations can be visualized on phylogenetic threes, and common ancestors of phenotype associated strains can be reconstructed and examined for functional clues at the nucleotide level. Moreover, most accessory genes can be linked to the species phylogeny and provide further functional insight to phenotype-associations.
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