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

By Sergey Koren, Brian Walenz, Konstantin Berlin, Jason Rafe Miller, Nicholas H. Bergman, Adam M. Phillippy. bioRxiv, 2016

6,453 citations recorded by the source corpus.

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 PacBio or Oxford Nanopore technologies, and achieves a contig NG50 of greater than 21 Mbp on both human and Drosophila melanogaster PacBio datasets. 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.

Subfields: Artificial Intelligence, Computer Networks and Communications, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2b59fd18ada769ef76fb7fcc7382f063791abfab

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Citations in the corpus

An improved de novo assembly and annotation of the tomato reference genome using single-molecule sequencing, Hi-C proximity ligation and optical maps (2019, methodology): “The Canu assembler (Koren et al. 2017) was used to assemble 80x coverage of PacBio long reads, generating 504 contigs.”
Assembly of long, error-prone reads using repeat graphs (2018, neutral): “Vertex B results in points (2, 5), (2, 10), and (5, 10); vertex C results in points (3, 6), (3, 11), and (6, 11); vertex D results in points (4, 7), (4, 12), and (7, 12); and vertex E results in the point (8, 13).”
Integrating Hi-C links with assembly graphs for chromosome-scale assembly (2018, methodology): “213 For real data, we use the recently published NA12878 human dataset sequenced with 214 Oxford Nanopore [34] and assembled with Canu [28].”
Major impacts of widespread structural variation on gene expression and crop improvement in tomato (2020, neutral): “These reads were then error corrected with Canu (corOutCoverage = 999, genomeSize = 475k) and assembled with Flye (–nano-corr,–genome-size 475k) (Kolmogorov et al., 2019; Koren et al., 2017).”
DNA sequencing at 40: past, present and future (2017, positive): “Long reads have resulted in a re-emergence of strategies used by the Celera assembler, improved to deal with the high error rates and multiple platforms 81 .”
NextDenovo: an efficient error correction and accurate assembly tool for noisy long reads (2024, methodology): “However, in terms of the assembly of segmental duplications/repeats, and especially for large plant genome assemblies, the CTA-based strategy usually has an enhanced ability to distinguish different gene copies and produce more accurate and continuous assemblies [14, 15, 18].”