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Title: Single-molecule sequencing and conformational capture enable de novo mammalian reference genomes

item Bickhart, Derek
item Rosen, Benjamin - Ben
item KOREN, SERGEY - National Institutes Of Health (NIH)
item SAYRE, BRIAN - Virginia State University
item HASTIE, ALEX - Bionano Genomics, Inc
item CHAN, SAKI - Bionano Genomics, Inc
item LEE, JOYCE - Bionano Genomics, Inc
item LAM, ERNEST - Bionano Genomics, Inc
item LIACHKO, IVAN - University Of Washington
item SULLIVAN, SHAWN - Collaborator
item BURTON, JOSH - University Of Washington
item HUSON, HEATHER - Cornell University
item Kelley, Christy
item Hutchison, Jana
item ZHOU, YANG - Collaborator
item SUN, JIAJIE - South China Agricultural University
item CRISA, ALESSANDRA - Agricultural Research Council (CRA)
item PONCE DE LEON, F - University Of Minnesota
item SCHWARTZ, JOHN - Pirbright Laboratory
item HAMMOND, JOHN - Pirbright Laboratory
item Waldbieser, Geoffrey - Geoff
item Schroeder, Steven - Steve
item Liu, Ge - George
item DUNHAM, MAITREYA - University Of Washington
item SHENDURE, JAY - University Of Washington
item SONSTEGARD, TAD - Former ARS Employee
item PHILLIPPY, ADAM - National Institutes Of Health (NIH)
item Van Tassell, Curtis - Curt
item Smith, Timothy - Tim

Submitted to: Nature Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/3/2017
Publication Date: 3/6/2017
Citation: Bickhart, D.M., Rosen, B.D., Koren, S., Sayre, B.L., Hastie, A.R., Chan, S., Lee, J., Lam, E.T., Liachko, I., Sullivan, S.T., Burton, J., Huson, H.J., Kelley, C.M., Hutchison, J.L., Zhou, Y., Sun, J., Crisa, A., Ponce De Leon, F.A., Schwartz, J.C., Hammond, J.A., Waldbieser, G.C., Schroeder, S.G., Liu, G., Dunham, M., Shendure, J., Sonstegard, T.S., Phillippy, A.M., Van Tassell, C.P., Smith, T.P. 2017. Single-molecule sequencing and conformational capture enable de novo mammalian reference genomes. Nature Genetics. 49(4):643-650.

Interpretive Summary: Reference genomes serve as an important baseline for future genetics research in Humans, model-organisms and other species; however, they are costly to create and validate. We present a new method, using state-of-the-art technologies, that allows us to create reference genomes for mammalian species at 0.01% of the cost of the original, year 2000, Human Reference Genome project. In order to demonstrate this technology, we construct a new reference genome for the domestic goat that is more than 1000-fold improved than a previous goat assembly version released in 2013, and was substantially less expensive to generate.

Technical Abstract: Genome assemblies have been produced for numerous species as a result of advances in sequencing technologies. However, many of the assemblies are fragmented, with many gaps, ambiguities, and errors. We use the genome of the domestic goat (Capra hircus) to demonstrate current state of the art for efficient de novo assembly, from initial contig formation using long reads, to scaffolding by optical mapping and chromatin interaction mapping. We show that this creates chromosome-length scaffolds containing only 663 gap regions. This represents an improvement in contiguity >1,000-fold over the published C. hircus assembly and >250-fold on the more recently released update. Our assembly better resolves repetitive structures greater than 1 kb in length, giving the most complete repeat family and immune complex representation for a ruminant and is the best de novo mammalian assembly to date. Our proposed combination technologies enable cost-effective reference-grade assemblies for mammalian genomes.