The transformation of DNA sequencing technologies has
enabled more powerful and comprehensive genetic profiling of microbes. The sheer
number of informative loci provided by genome-sequencing allows the
investigation of structural variation and horizontal gene transfer as well as
delivering novel insights into genetic origins, evolution and epidemiological
history. Microbial genomes can be sequenced en masse at high coverage but have associated
challenges of high mutation rates and low conservation of genome structure.
Consequently, detecting changes in DNA sequences requires a nuanced approach
specific to the organism, availability of similar genomes, and types of
variation. Here, we outline the high power of genome-sequencing to detect a
wide scope of polymorphism classes.
Samples without related species on which to scaffold a genome sequence
require specific assembly methods that can be enhanced by progressive
procedures for improvement. Polymorphism identification depends on genome
structure, and error rates in closely related specimens can be reduced by
incorporating population-level information. The development of genome analysis platforms
is hastening the optimisation of variant discovery and has direct applications
for pathogen surveillance. Robust variant screening facilitates more sensitive
scrutiny of population history, including the origin and emergence of
infectious agents, and a deeper understanding of the selective processes that
shape microbial phenotypes.