Assembling Large Genomes with Single-Molecule Sequencing and Locality Sensitive Hashing

BioRxiv : the Preprint Server for Biology
Konstantin BerlinAdam M Phillippy

Abstract

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.

Related Concepts

Chromosomes
Drosophila melanogaster
Escherichia coli
Genome
Saccharomyces cerevisiae
Arabidopsis thaliana <plant>
Research Activities
Molecular Assembly/Self Assembly
Drosophila melanogaster Proteins
Small Molecule

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