RT Journal Article SR Electronic T1 Assembling Large Genomes with Single-Molecule Sequencing and Locality Sensitive Hashing JF bioRxiv FD Cold Spring Harbor Laboratory SP 008003 DO 10.1101/008003 A1 Konstantin Berlin A1 Sergey Koren A1 Chen-Shan Chin A1 James Drake A1 Jane M. Landolin A1 Adam M. Phillippy YR 2014 UL http://biorxiv.org/content/early/2014/08/14/008003.abstract AB We report reference-grade de novo assemblies of four model organisms and the human genome from single-molecule, real-time (SMRT) sequencing. Long-read SMRT sequencing is routinely used to finish microbial genomes, but the available assembly methods have not scaled well to larger genomes. Here we introduce the MinHash Alignment Process (MHAP) for efficient overlapping of noisy, long reads using probabilistic, locality-sensitive hashing. Together with Celera Assembler, MHAP was used to reconstruct the genomes of Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster, and human from high-coverage SMRT sequencing. The resulting assemblies include fully resolved chromosome arms and close persistent gaps in these important reference genomes, including heterochromatic and telomeric transition sequences. For D. melanogaster, MHAP achieved a 600-fold speedup relative to prior methods and a cloud computing cost of a few hundred dollars. These results demonstrate that single-molecule sequencing alone can produce near-complete eukaryotic genomes at modest cost.