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.

Keywords

GenomeComputational biologySequence assemblyBiologyHybrid genome assemblyReference genomeDrosophila melanogasterGeneticsComputer scienceGene

MeSH Terms

AnimalsArabidopsisBase SequenceChromosomesDrosophila melanogasterGenomeFungalGenomeHumanGenomeInsectGenomePlantHeterochromatinHigh-Throughput Nucleotide SequencingHumansSaccharomyces cerevisiaeSequence AlignmentSequence AnalysisDNA

Affiliated Institutions

Related Publications

De novo assembly of human genomes with massively parallel short read sequencing

Ruiqiang Li , Hongmei Zhu , Jue Ruan +11 more

Next-generation massively parallel DNA sequencing technologies provide ultrahigh throughput at a substantially lower unit data cost; however, the data are very short read length...

2009 Genome Research 2939 citations

Whole-Genome Sequencing and Assembly with High-Throughput, Short-Read Technologies

Andreas Sundquist , Mostafa Ronaghi , Haixu Tang +2 more

While recently developed short-read sequencing technologies may dramatically reduce the sequencing cost and eventually achieve the $1000 goal for re-sequencing, their limitation...

2007 PLoS ONE 126 citations

GAGE: A critical evaluation of genome assemblies and assembly algorithms

Steven L. Salzberg , Adam M. Phillippy , Aleksey V. Zimin +10 more

New sequencing technology has dramatically altered the landscape of whole-genome sequencing, allowing scientists to initiate numerous projects to decode the genomes of previousl...

2011 Genome Research 733 citations

SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing

Anton Bankevich , Sergey Nurk , Dmitry Antipov +13 more

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell gen...

2012 Journal of Computational Biology 25356 citations

SHARCGS, a fast and highly accurate short-read assembly algorithm for de novo genomic sequencing

Juliane C. Dohm , Claudio Lottaz , Tatiana Borodina +1 more

The latest revolution in the DNA sequencing field has been brought about by the development of automated sequencers that are capable of generating giga base pair data sets quick...

2007 Genome Research 281 citations

Publication Info

Year: 2015
Type: article
Volume: 33
Issue: 6
Pages: 623-630
Citations: 985
Access: Closed

External Links

Download PDF (Free) View on DOI.org PubMed Semantic Scholar

Social Impact

Altmetric

Assembling large genomes with single-molecule sequencing and locality-sensitive hashing

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

985

OpenAlex

Influential

Cite This

APA Style

                            
                                
                                    Konstantin Berlin, 
                                
                                    Sergey Koren, 
                                
                                    Chen-Shan Chin
                                
                                et al.
                            
                            (2015). 
                            Assembling large genomes with single-molecule sequencing and locality-sensitive hashing. 
                            Nature Biotechnology
                            , 33
                            (6)
                            , 623-630.
                            https://doi.org/10.1038/nbt.3238
                        

Identifiers

DOI: 10.1038/nbt.3238
PMID: 26006009

Data Quality

Data completeness: 90%