Assembly of long, error-prone reads using repeat graphs

By Mikhail Kolmogorov, Jeffrey Yuan, Yu Lin, Pavel A. Pevzner. Nature Biotechnology, 2018

4,871 citations recorded by the source corpus.

Accurate genome assembly is hampered by repetitive regions. Although long single molecule sequencing reads are better able to resolve genomic repeats than short-read data, most long-read assembly algorithms do not provide the repeat characterization necessary for producing optimal assemblies. Here, we present Flye, a long-read assembly algorithm that generates arbitrary paths in an unknown repeat graph, called disjointigs, and constructs an accurate repeat graph from these error-riddled disjointigs. We benchmark Flye against five state-of-the-art assemblers and show that it generates better or comparable assemblies, while being an order of magnitude faster. Flye nearly doubled the contiguity of the human genome assembly (as measured by the NGA50 assembly quality metric) compared with existing assemblers. Flye improves the speed and accuracy of genome assembly by using repeat graphs to resolve repeat regions.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/e0f860a608ecfb4ac6d0010e16db5c13cca14da1

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Citations in the corpus

NextDenovo: an efficient error correction and accurate assembly tool for noisy long reads (2024, background): “…errors in the assembled genome); the former (such as Necat [14] and Canu [15]) is usually slower than the latter (such as Wtdbg2 [16] and Flye [17]), because read-level error correction requires much more computational resources than contig-level polishing (a step to correct errors in the…”
Long-read human genome sequencing and its applications (2020, neutral): “This more than 100-fold increase in assembly 74 , FALCON 75 , Flye 76 , wtdbg2 (or RedBean) 77 and Shasta 36 ) and other tools that can increase assembly .”
De novo assembly of haplotype-resolved genomes with trio binning (2018, neutral): “Because trio binning outputs two sets of haplotype-specific reads, it is compatible with any long-read assembler 20, 42, 43 and repeat separation technique 44 for assembling the individual haplotypes.”
Haplotype-resolved diverse human genomes and integrated analysis of structural variation (2021, methodology): “Strand-seq data were produced from the same samples and used to identify and phase heterozygous SNVs [LongShot (66) and DeepVariant (67)] from the squashed genome assemblies [Peregrine (68) or Flye (69)].”
Major impacts of widespread structural variation on gene expression and crop improvement in tomato (2020, positive): “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).”
The complete sequence of a human genome (2021, methodology): “A GA-rich region in the p-arm pseudoautosomal region (PAR) was patched with a Flye (96) trio-binned (97) and medaka polished assembly.”
HiCanu: accurate assembly of segmental duplications, satellites, and allelic variants from high-fidelity long reads (2020, methodology): “Despite the per-base error rate of the input reads exceeding 10%, state-of-the-art assemblymethods are able to resolve instances of longer repeats with sequence divergence as low as 2% (Koren et al. 2017; Kolmogorov et al. 2019).”
Integrating Hi-C links with assembly graphs for chromosome-scale assembly (2018, positive): “Since most long read genome assemblers such as FALCON (Chin et al. , 2016), miniasm (Li, 2016), Canu (Koren et al. , 2017), and Flye (Kolmogorov et al. , 2018) provide assembly graphs in GFA format, their output is compatible with SALSA2 for scaffolding.”