Chromosome-scale scaffolding of de novo genome assemblies based on chromatin interactions

By Joshua N. Burton, Andrew C. Adey, Rupali Patwardhan, R. Qiu, J. Kitzman, Jay Shendure. Nature Biotechnology, 2013

1,327 citations recorded by the source corpus.

Genomes assembled de novo from short reads are highly fragmented relative to the finished chromosomes of Homo sapiens and key model organisms generated by the Human Genome Project. To address this problem, we need scalable, cost-effective methods to obtain assemblies with chromosome-scale contiguity. Here we show that genome-wide chromatin interaction data sets, such as those generated by Hi-C, are a rich source of long-range information for assigning, ordering and orienting genomic sequences to chromosomes, including across centromeres. To exploit this finding, we developed an algorithm that uses Hi-C data for ultra-long-range scaffolding of de novo genome assemblies. We demonstrate the approach by combining shotgun fragment and short jump mate-pair sequences with Hi-C data to generate chromosome-scale de novo assemblies of the human, mouse and Drosophila genomes, achieving—for the human genome—98% accuracy in assigning scaffolds to chromosome groups and 99% accuracy in ordering and orienting scaffolds within chromosome groups. Hi-C data can also be used to validate chromosomal translocations in cancer genomes.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/4b69b9c0f673edff9f09469a499abcafa8089c66

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Citations in the corpus

DNA sequencing at 40: past, present and future (2017, neutral): “Secondly, methods, such as Hi-C (genome-wide chromosome conformation capture) and optical mapping, provide scalable, cost-effective means of scaffolding genomes into chromosome-scale assemblies 78–80 .”
Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation (2016, background): “Combining the Canu assembly graph with supple-mentarylong-range information,suchas fromoptical(Hastie et al. 2013) or chromatin contact mapping (Burton et al. 2013; Kaplan and Dekker 2013), could help identify the correct path and resolve such structures.”
De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds (2016, methodology): “Comparison of scaffolding algorithms presented in (10) and the current paper.”
Computational pan-genomics: status, promises and challenges (2016, background): “Presently, array comparative genomic hybridization (arrayCGH), synthetic long reads (Moleculo [87], 10X Genomics [88]), chromatin interaction measurements [89] and high-throughput optical mapping [90–92] all aid the detection of structural variation.”
The Juicebox Assembly Tools module facilitates de novo assembly of mammalian genomes with chromosome-length scaffolds for under $1000 (2018, methodology): “Hi-C contact maps are valuable for genome assembly (Lieberman-Aiden, van Berkum et al. 2009; Burton et al. 2013; Dudchenko et al. 2017).”
The Third Revolution in Sequencing Technology. (2018, neutral): “Another example is chromosome conformation capture [45].”
YaHS: yet another Hi-C scaffolding tool (2022, positive): “Since the contact frequency between loci pairs strongly correlates with separation on the genome, Hi-C has rapidly gained popularity as an economical method for generating chromosome-scale scaffolds (Burton et al. , 2013; Dudchenko et al. , 2017).”