MicrobesNG: A scalable replicable biological sample repository incorporating whole-genome sequence data and analysis of thousands of microbial strains

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One of the greatest advances of modern science is the ability to determine the DNA sequences of living organisms. Access to complete DNA sequences has provided researchers, environmentalists, clinicians, law enforcement and industrialists with a myriad of benefits. The information permits a deeper understanding of the diversity of life in the world. Comparing DNA sequences allows researchers to determine relationships between the three kingdoms of life and to infer evolutionary lineages. Understanding the genetic content of animals and plants permits the selection and development of stronger, more disease-resistant plants and animals increasing outputs and reducing waste. Understanding the human and animal genomes has had an enormous impact on the ability of clinicians to determine genetic susceptibility to a variety of diseases; one only has to witness the lives saved by identifying those most at risk of breast cancer and offering early treatment. The ability to harness genome information has allowed industry to develop new therapies for disease and produce new methods for a variety of manufacturing processes e.g. .enzymes are being used to bleach paper pulp. To the lay person, perhaps the most familiar benefit to genomic data is the use of DNA to identify perpetrators of crime. One of the subjects to benefit most from genome sequencing is microbiology. The ability to rapidly obtain genome sequences has allowed researchers to find new bacterial and viral genes which allow pathogens to cause disease. It allows epidemiologists to identify strains in outbreaks of infection and to trace those outbreaks back to the point of origin so further infections can be prevented. Genome sequencing has elucidated mechanisms by which bacteria become resistant to antibiotics allowing clinicians to use a more informed decision making process when prescribing antibiotics. Microbial genomics helps the pharmaceutical industry gain a better understanding of the vulnerabilities of bacteria and viruses, information which is used to identify and develop new drugs. Recently, genomic studies have linked changes in certain bacterial populations growing in and on the human body with non-infectious disease such as obesity and cancer.The tremendous success of genome sequencing has provided us with a problem. Rapid technological advances in DNA sequencing have resulted in the ability of researchers to generate sequence data quicker than it can be analysed and interpreted with current methodologies. This is for a number of different reasons including the development of ad-hoc methods to prepare, analyse and store the data and the lack of standard operating procedures across the discipline. Importantly, the ability to rapidly sequence bacterial genomes in particular, means thousands of strains are being sequenced yet there is no common method for accessing and studying these strains and garnering the benefits of this significant investment of Public money.This proposal seeks to redress some of the problems that have become apparent in the community. We will establish a resource that becomes a paradigm for sequencing bacterial strains, for storing and analysing the genomic data, and for archiving sequenced strains so they can be interrogated later. We will achieve this by (1) establishing best practices for sequencing protocols that deliver maximum output, (2) providing a framework to efficiently manage the storage of collections of bacterial strains, (3) developing software that allows whole-genome sequencing data and meta-data (information on the source, and characteristics of the strain) to be correlated with strains in the store and (4) delivering novel analysis tools to permit the comparison of hundreds or thousands of microbial strains simultaneously, thereby easing the analysis bottleneck. We will make these tools and protocols available to the wider community so that they can be adopted by genome sequencing centres in other disciplines.