PT  - JOURNAL ARTICLE
AU  - Konstantin Berlin
AU  - Sergey Koren
AU  - Chen-Shan Chin
AU  - James Drake
AU  - Jane M. Landolin
AU  - Adam M. Phillippy
TI  - Assembling Large Genomes with Single-Molecule Sequencing and Locality Sensitive Hashing
AID  - 10.1101/008003
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 008003
4099  - http://biorxiv.org/content/early/2014/08/14/008003.short
4100  - http://biorxiv.org/content/early/2014/08/14/008003.full
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.