An in vitro method for generating long-range read pair data for genomic assembly and analysis.

DESCRIPTION provided by applicant The production of whole genome sequences de novo assembly is fundamental to both basic and clinical genomics research in the areas of gene regulation structural variant detection haplotype phasing and metagenomics analysis The fold reduction in raw Next Generation DNA Sequencing NGS costs the past seven years has made genomics research much more affordable However while economical these technologies currently produce highly fragmented genome assemblies Dovetail Genomics has developed a novel and cost effective Multi Scale Linking MSL sequencing library that leverages existing NGS technology to improve the median assembly size N over fold from less than kbp to greater than Mbp Our service will utilize these libraries and our novel assembly algorithms to produce high quality more complete genomes beginning from only DNA no cells or tissue required Furthermore we will do so rapidly less than one month and economically less than $ Our service can also be used to improve existing assemblies for less than $ A principal feature of these libraries that enables such improvement is the production of genomic read pairs spanning many scales and extremely long distances Our software pipeline leverages this feature to produce more contiguous and complete genome assemblies Our long term goal with the provision of these high quality genomes is the improvement of human health and the expansion of human knowledge of ourselves and other organisms Higher quality genomes enable more powerful studies and understanding of human genomic disease They also place personalized medicine within reach via the rapid and affordable provision of individual patient genomes In Dovetailandapos s first year we demonstrated the feasibility of our technologiesandapos capability to increase genome assembly contiguity fold Moving forward we are striving to refine both our library production and analysis platforms to a commercially viable level This will require increasing the value of the data produced by our proprietary sequencing libraries and refining and deploying our assembly pipeline and other analysis software Our specific aims to accomplish this feat are Increase the efficiency and genomic range of our library production platform Improve our existing prototype assembly pipeline optimizing speed and scalability by transitioning to cloud based compute infrastructure Improve existing pipelines for genomic phasing and the detection and characterization of structural variation in humans for clinical genomics There are commercial opportunities for such a service in both academic and clinical research as well as in the clinic itself Sufficiently complete and cost effective genome assemblies will enable broader and more powerful studies of genomes at both the population and individual level In clinical research where large patient cohorts are the norm they will enable the discovery and description of genomic drivers of human disease And in the clinic itself they will enable the rapid acquisition of patient genomes for diagnosis and treatment of many diseases including and especially cancer PUBLIC HEALTH RELEVANCE Many genomic diseases including and especially cancer are associated with large rearrangements in the genome that can only be adequately discovered and characterized with long range genomic sequence information Similarly knowledge of the inheritance patterns of genomic variants associated with disease and the economical acquisition of personal genomes for medical purposes benefit tremendously from the same information Consequently the attainment of extremely long range genomic sequence information has significant implications for human health particularly for the study and treatment of genomic diseases