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Showing content from http://www.genome.org/cgi/doi/10.1101/gr.215087.116 below:

scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation

1. Sergey Koren1,5,
2. Brian P. Walenz1,5,
3. Konstantin Berlin2,
4. Jason R. Miller3,
5. Nicholas H. Bergman4 and
6. Adam M. Phillippy1

1. ¹Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
2. ²Invincea Incorporated, Fairfax, Virginia 22030, USA;
3. ³J. Craig Venter Institute, Rockville, Maryland 20850, USA;
4. ⁴National Biodefense Analysis and Countermeasures Center, Frederick, Maryland 21702, USA

1. Corresponding author: adam.phillippy{at}nih.gov

1. ↵5 These authors contributed equally to this work.

Long-read single-molecule sequencing has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. However, given the relatively high error rates of such technologies, efficient and accurate assembly of large repeats and closely related haplotypes remains challenging. We address these issues with Canu, a successor of Celera Assembler that is specifically designed for noisy single-molecule sequences. Canu introduces support for nanopore sequencing, halves depth-of-coverage requirements, and improves assembly continuity while simultaneously reducing runtime by an order of magnitude on large genomes versus Celera Assembler 8.2. These advances result from new overlapping and assembly algorithms, including an adaptive overlapping strategy based on tf-idf weighted MinHash and a sparse assembly graph construction that avoids collapsing diverged repeats and haplotypes. We demonstrate that Canu can reliably assemble complete microbial genomes and near-complete eukaryotic chromosomes using either Pacific Biosciences (PacBio) or Oxford Nanopore technologies and achieves a contig NG50 of >21 Mbp on both human and Drosophila melanogaster PacBio data sets. For assembly structures that cannot be linearly represented, Canu provides graph-based assembly outputs in graphical fragment assembly (GFA) format for analysis or integration with complementary phasing and scaffolding techniques. The combination of such highly resolved assembly graphs with long-range scaffolding information promises the complete and automated assembly of complex genomes.

• [Supplemental material is available for this article.]

• Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.215087.116.

• Freely available online through the Genome Research Open Access option.

• Received August 23, 2016.
• Accepted March 3, 2017.

• © 2017 Koren et al.; Published by Cold Spring Harbor Laboratory Press

This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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