Explaining microbial phenotypes on a genomic scale: GWAS for microbes

There is an increasing availability of complete or draft genome sequences for microbial organisms. These data form a potentially valuable resource for genotype–phenotype association and gene function prediction, provided that phenotypes are consistently annotated for all the sequenced strains. In this review, we address the requirements for successful gene-trait matching. We outline a basic protocol for microbial functional genomics, including genome assembly, annotation of genotypes (including single nucleotide polymorphisms, orthologous groups and prophages), data pre-processing, genotype–phenotype association, visualization and interpretation of results. The methodologies for association described herein can be applied to other data types, opening up possibilities to analyze transcriptome–phenotype associations, and correlate microbial population structure or activity, as measured by metagenomics, to environmental parameters.