Microbiology is embracing high-throughput genomics. The power of differentiation and the ability to follow evolutionary changes from the genome to the allele is very powerful. Many long-standing evolutionary questions, as well as new questions can be addressed using WGS and metagenomics. The unprecedented resolution is extremely powerful. With the increase in production of WGS and release into the public domain, every it is creating the need ever increasing computational capabilities that link function to genome characteristics in many settings. G4H is directly producing and analyzing genomic information that is important worldwide for pathogens and metagenomes from agriculture, public health, and the environment.

This effort has produced an unprecedented perspective of biogeography and bacterial evolution with the observation that bacterial genomes are unexpectedly diversity and is a function of the number of sequences that are examined. Using extremely large data sets (>10,000 genomes) new genes are being found with every new sequence, we are examining the genotype with increasing resolution to define the global location, disease association, virulence potential and create new diagnostics to accompany control strategies.

This work is using advanced sequencing technologies to produce draft and closed genomes that provide unparalleled scale with machine learning tools to uncover genotypes and their link to disease and persistence. Independently, and in cooperation with groups around the world, we have sequenced genomes and metagenomes that provide a view of how communities change with small genotype variation. This approach is enabling systematic definition of a biomarker gene sets associated with persistence, serotype diversity, location, antibiotic resistance, pathogenesis, and host association – just to name a few applications.


Using a mix of WGS and metagenomics we have uncovered antibiotic resistance gene movement, directed selection of antibiotics to resolve disease, definition of zoonotic genotypes, and discovery of pathogens evolving to carrier genotypes. Extensive analysis of genomes is facilitate a new era in microbial genomics by increasing the speed of genome production to near real-time directly with a level of precision and accuracy that has never been seen and cannot be achieved with existing methods. 

Genomics-enabled diagnostics with molecular tools for surveillance, risk assessment, and pathogen diagnostics directly from sample to genome result in hours rather than days. For example, samples from farms, processing facilities, the transportation chain, and supermarkets are the direct outcome of this project. This is also applicable to clinics and One Health applications. Additionally, coupling this approach to culture-independent methods using capture/concentration methods provides a near real-time answer that is anchored in the DNA and RNA contained in an organism residing in the sample.