Comparison of functional classification systems

In microbiome analysis, functional profiling is based on assigning reads or contigs to terms or nodes in a functional classification system. There are a number of large, general-purpose functional classifications that are in use, such as eggNOG, KEGG, InterPro and SEED. Smaller, special-purpose classifications include CARD, EC, MetaCyc and VFDB. Here, we compare the different classifications in terms of their overlap, redundancy, structure and assignment rates. We also provide mappings between main concepts in different classifications. For the large classifications, we find that eggNOG performs the best with respect to sequence redundancy and structure, SEED has the cleanest hierarchy, whereas KEGG and InterPro:BP might be more informative for medical applications. We illustrate the practical assignment rates for different classifications using a number of metagenomic samples.