title: Assembling large genomes with single-molecule sequencing and locality-sensitive hashing.
abstract: Long-read, single-molecule real-time (SMRT) sequencing is routinely used to finish microbial genomes, but available assembly methods have not scaled well to larger genomes. We introduce the MinHash Alignment Process (MHAP) for overlapping noisy, long reads using probabilistic, locality-sensitive hashing. Integrating MHAP with the Celera Assembler enabled reference-grade de novo assemblies of Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster and a human hydatidiform mole cell line (CHM1) from SMRT sequencing. The resulting assemblies are highly continuous, include fully resolved chromosome arms and close persistent gaps in these reference genomes. Our assembly of D. melanogaster revealed previously unknown heterochromatic and telomeric transition sequences, and we assembled low-complexity sequences from CHM1 that fill gaps in the human GRCh38 reference. Using MHAP and the Celera Assembler, single-molecule sequencing can produce de novo near-complete eukaryotic assemblies that are 99.99% accurate when compared with available reference genomes.
authors.affiliation: 1] Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA. [2] Institute for Advanced Computer Studies, University of Maryland, College Park, Maryland, USA. [3] Invincea Labs, Arlington, Virginia, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Berlin
authors.affiliation: National Biodefense Analysis and Countermeasures Center, Frederick, Maryland, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Koren
authors.affiliation: Pacific Biosciences of California, Inc., Menlo Park, California, USA.
authors.forename: Chen-Shan
authors.identifier: 0000000343942455
authors.initials: CS
authors.lastname: Chin
authors.affiliation: Pacific Biosciences of California, Inc., Menlo Park, California, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Drake
authors.affiliation: Pacific Biosciences of California, Inc., Menlo Park, California, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Landolin
authors.affiliation: National Biodefense Analysis and Countermeasures Center, Frederick, Maryland, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Phillippy
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D001483:Base Sequence; D002875:Chromosomes / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D016681:Genome, Fungal; D015894:Genome, Human; D049750:Genome, Insect; D018745:Genome, Plant; D006570:Heterochromatin; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D006570:Heterochromatin