A high-throughput platform for assembling genome data: the Saphyr

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Since the completion of the human genome project in 2003, after 13 years of work and billions of dollars, the ability to produce genomic data has accelerated at phenomenal rates. Advances in sequencing technologies mean that just 20 years on we can now sequence a genome in hours, not years, at the cost of a few hundred dollars. As such, genome sequence data can be produced by small and large labs alike, and numerous regional, national and global consortia have been newly launched with the goal of sequencing millions of species worldwide in the coming years.Unfortunately, while the explosion of thousands of genome datasets has created new opportunities - such as screening genomes for variants that correlate with ecologically-important traits such as disease resistance - it has also created equally steep challenges. A particular problem concerns the nature of genomic datasets; even after deep-sequencing, most "genomes" actually comprise large numbers of non-contiguous fragments that cannot be stitched together into chromosomes. This incomplete assembly obstructs inferences of linkage, synteny, and genotype-phenotype association, and is especially severe for non-model plants, fungi and animals that are characterised by large complex genomes. The Saphyr platform (Bionano Genomics) overcomes this obstacle by directly imaging megabase length fluorescently barcoded optical molecules. DNA is treated with an enzyme that deposits fluorescent marks based at specific sites, and then millions of large DNA molecules are passed through proprietary nanochannels and their images are converted to graphical barcodes. Using software, barcoded molecules are compared against each other, and, based on matching patterns of fluro-marks, assembled into 'optical contigs'; these are structural scaffolds, independent of sequence, that represent very large regions. Since these contigs easily span breaks in sequence assembly, they allow the generation of chromosome length 'hybrid scaffolds' made up of optical and sequence contigs, where the short-read sequence assemblies have been in silico enzyme treated so that they exhibit the same barcode patterns as the optical molecules.Optical mapping is considered an essential step in producing high quality genomes, and features in the pipelines used by many large sequencing consortia, including the newly-launched Darwin Tree of Life Project, which aims to capture the genomic information of the ~66,000 UK species. The Saphyr is the only high-throughput optical mapping platform, yet there is currently no dedicated facility for NERC-funded research working at the interface of genomics and environmental science.We will establish a NERC-oriented next generation optical mapping facility at QMUL, underpinned by our technical support for isolating ultra-high molecular weight DNA from a range of biological samples and species. This high throughout facility will meet current demand for generating high quality genomes, and will thus enhance the UK's technical capacity in the fast developing field of environmental genomics. Specifically, the facility will enable researchers to (1) include genome assemblies in current and future projects, (2) play more active roles in large genome networks, and (3) exploit the platform's versatility to tackle novel research questions regarding the genome-wide distributions of specific DNA motifs and features. At an institutional level, the Saphyr will allow us to expand our research portfolio and address fundamental questions in ecological and evolutionary genomics in diverse non-model organisms, which range from trees and bacteria to mammals and annelids. Moreover, the Saphyr will enhance training of specialised staff, enhance our capacity to establish collaborations with other UK research institutions, and thus emerge as a common technical resource for the environmental-oriented research community.