The Human Pangenome Project: a global resource to map genomic diversity

Wang, Ting; Antonacci-Fulton, Lucinda; Howe, Kerstin; Lawson, Heather A.; Lucas, Julian; Phillippy, Adam M.; Popejoy, Alice B.; Asri, Mobin; Carson, Caryn; Chaisson, Mark; Chang, Xian; Cook-Deegan, Robert; Felsenfeld, Adam; Fulton, Robert S.; Garrison, Erik; Garrison, Nanibaa’ A.; Graves-Lindsay, Tina A.; Ji, Hanlee P.; Kenny, Eimear E.; Koenig, Barbara A.; Li, Daofeng; Marschall, Tobias; McMichael, Joshua F.; Novak, Adam M.; Purushotham, Deepak; Schneider, Valérie; Schultz, Baergen I; Smith, Michael W.; Sofia, Heidi J.; Weissman, Tsachy; Flicek, Paul; Li, Heng; Miga, Karen H.; Paten, Benedict; Jarvis, Erich D.; Hall, Ira M.; Eichler, Evan E.; Haussler, David

doi:10.1038/s41586-022-04601-8

Cited by 262 publications

(264 citation statements)

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“…We ran Verkko on the benchmark HG002 human sample from Genome in a Bottle (GIAB) 42 and the Human Pangenome Reference Consortium (HPRC) 43 (Data availability). We used the downsampled 35× dataset base-called with DeepConsensus, which has been shown to improve coverage and assembly quality 44 , along with 60× ONT ultra-long reads.…”

Section: Resultsmentioning

confidence: 99%

Verkko: telomere-to-telomere assembly of diploid chromosomes

Rautiainen

Nurk

Walenz

et al. 2022

Preprint

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The Telomere-to-Telomere consortium recently assembled the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on manual integration of ultra-long Oxford Nanopore sequencing reads with a high-resolution assembly graph built from long, accurate PacBio HiFi reads. We have improved and automated this strategy in Verkko, an iterative, graph-based pipeline for assembling complete, diploid genomes. Verkko begins with a multiplex de Bruijn graph built from long, accurate reads and progressively simplifies this graph via the integration of ultra-long reads and haplotype-specific markers. The result is a phased, diploid assembly of both haplotypes, with many chromosomes automatically assembled from telomere to telomere. Running Verkko on the HG002 human genome resulted in 20 of 46 diploid chromosomes assembled without gaps at 99.9997% accuracy. The complete assembly of diploid genomes is a critical step towards the construction of comprehensive pangenome databases and chromosome-scale comparative genomics.

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Section: Resultsmentioning

confidence: 99%

Verkko: telomere-to-telomere assembly of diploid chromosomes

Rautiainen

Nurk

Walenz

et al. 2022

Preprint

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“…To further explore the diversity of KIV-2 region, we obtained 47 Pacbio HiFi based long read assemblies that are phased and highly contiguous [28][29][30] . These 47 assemblies span a wide variety of samples from the United States and its territories (e.g.…”

Section: Resultsmentioning

confidence: 99%

A pan-genome approach to decipher variants in the highly complex tandem repeat ofLPA

Chin

Behera

Metcalf

et al. 2022

Preprint

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Lp(a) is an important factor in Coronary Heart disease risk, and its expression is correlated with the length of the LPA gene. The KIV-2 region of LPA consists of variable tandem repeats whose number is highly variable across individuals. Little is known about the inner diversity of the KIV-2 repeats themselves. Here we utilize a pan-genome graph approach across 47 haplotype resolved assemblies to identify unexpected variations across KIV-2.

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“…Notably, most recent population-scale studies of SVs have used pan-genomic models to eliminate reference bias and successfully scaled up the population size for genotyping from a few hundred to thousands of samples [4] , [32] , [63] , [64] , [65] , facilitating other genotype-based downstream analyses. Recently, the Telomer-to-Telomere (T2T) Consortium and the Human Pangenome Reference Consortium have successively announced their exciting progress in constructing complete and error-free T2T assemblies of all chromosomes as well as full-spectrum genomic variant collections [116] , [117] , [118] , which will further promote the application of pan-genomic approaches in population genetic studies.…”

Section: Discussionmentioning

confidence: 99%

Population-scale genotyping of structural variation in the era of long-read sequencing

Cheng

et al. 2022

Computational and Structural Biotechnology Journal

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The Human Pangenome Project: a global resource to map genomic diversity

Cited by 262 publications

References 100 publications

Verkko: telomere-to-telomere assembly of diploid chromosomes

Verkko: telomere-to-telomere assembly of diploid chromosomes

A pan-genome approach to decipher variants in the highly complex tandem repeat ofLPA

Population-scale genotyping of structural variation in the era of long-read sequencing

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