Application of genome-scale analysis like DNA microarray technology has revolutionized multiple scientific disciplines. Herein, a next generation of DNA microarrays, a DNA tiling approach that allows high throughput sampling of genomes with single-nucleotide precision, is described. As methods revealing a genomic scale examination of cellular phenotypes offer keen insights for genomic analyses, a high throughput system for whole cell phenotyping is similarly detailed. The merit of these technologies in discriminating pathogenic and commensal strains of microbes is emphasized using the microbe, Escherichia coli, as an example. Deployment of microarray strategies to assess closely-related microbial strains should help address diversity of organisms in their feral settings.