Pan-genomics in the human genome era

Sherman, Rachel M.; Salzberg, Steven L.

doi:10.1038/s41576-020-0210-7

Cited by 239 publications

(220 citation statements)

References 101 publications

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“…For example, the highly variable major histocompatibility complex (MHC) is excluded from the Genome in a Bottle (GIAB) and Global Alliance for Genomic Health (GA4GH) reference panels [26] due to its repetitive nature and need of a specialized mapping strategy to account for the high allelic diversity [29]. Moreover, reference-guided strategies require significant manual curation and effort and will not scale as large cohort sequencing projects become common [30,31]. This validation strategy is also not applicable to any species without a curated and complete reference [32].…”

Section: Introductionmentioning

confidence: 99%

Merqury: reference-free quality, completeness, and phasing assessment for genome assemblies

et al. 2020

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Recent long-read assemblies often exceed the quality and completeness of available reference genomes, making validation challenging. Here we present Merqury, a novel tool for reference-free assembly evaluation based on efficient k-mer set operations. By comparing k-mers in a de novo assembly to those found in unassembled high-accuracy reads, Merqury estimates base-level accuracy and completeness. For trios, Merqury can also evaluate haplotype-specific accuracy, completeness, phase block continuity, and switch errors. Multiple visualizations, such as k-mer spectrum plots, can be generated for evaluation. We demonstrate on both human and plant genomes that Merqury is a fast and robust method for assembly validation.

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Section: Introductionmentioning

confidence: 99%

Merqury: reference-free quality, completeness, and phasing assessment for genome assemblies

et al. 2020

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“…In the future, pan-genome representations and graph-based algorithms will likely change the way reference genomes are represented and analyzed (25,11). Since linear genomes are still widely used, their improvements are relevant (11) and our work demonstrates that significant enhancements can be obtained with efficient use of the existing data. Moreover, characterization of haplotypes is instrumental in more inclusive genome representations, increasing the relevance of our approach.…”

Section: Discussionmentioning

confidence: 84%

Automated improvement of stickleback reference genome assemblies with Lep-Anchor software

Kivikoski

Rastas

Löytynoja

et al. 2020

Preprint

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The utility of genome-wide sequencing data in biological research depends heavily on the quality of the reference genome. Although the reference genomes have improved, it is evident that the assemblies could still be refined, especially in non-model study organisms. Here, we describe an integrative approach to improve contiguity and haploidy of a reference genome assembly. With two novel features of Lep-Anchor software and a combination of dense linkage maps, overlap detection and bridging long reads we generated an improved assembly of the nine-spined stickleback (Pungitius pungitius) reference genome. We were able to remove a significant number of haplotypic contigs, detect more genetic variation and improve the contiguity of the genome, especially that of X chromosome. However, improved scaffolding cannot correct for mosaicism of erroneously assembled contigs, demonstrated by a de novo assembly of a 1.7 Mbp inversion. Qualitatively similar gains were obtained with the genome of three-spined stickleback (Gasterosteus aculeatus).

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“…Since the publication of the first human genome [59,60] , and the first surveys of worldwide variation such as the 1,000 Genomes project [13,38], the efforts have been directed to expand outwards by expanding the exploration of the human diversity across the world, and filling out more and more "white spots" of genome variation [12,45], as well as inward, to fill the remaining white spots in the human genome itself: to map the remaining gaps in the chromosome assembly and identify new structural and functional variation [61] and to map the three dimensional structure of the human genome [62]. The new data presents a valuable addition to the former and represents the first exploration of the genome landscape in the important component of European genomic diversity.…”

Section: Re-use Potentialmentioning

confidence: 99%

Genome Diversity in Ukraine

Oleksyk

Wolfsberger

Weber

et al. 2020

Preprint

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The main goal of this collaborative effort is to provide genome wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for the public data release. DNBSEQ-G50 sequences, and genotypes by an Illumina GWAS chip were cross-validated on multiple samples, and additionally referenced to a sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. The genome data has been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, CNVs, SNPs and microsatellites. This study is providing the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for historic and medical research in a large understudied population. While most of the common variation is shared with other European populations, this survey of population variation contributes a number of novel SNPs and structural variants that have not been reported in the gnomAD/1KG databases representing global distribution of genomic variation. These endemic variants will become a valuable resource for designing future population and clinical studies, help address questions about ancestry and admixture, and will fill a missing place in the puzzle characterizing human population diversity in Eastern Europe. Our results indicate that genetic diversity of the Ukrainian population is uniquely shaped by the evolutionary and demographic forces, and cannot be ignored in the future genetic and biomedical studies. This data will contribute a wealth of new information bringing forth different risk and/or protective alleles. The newly discovered low frequency and local variants can be added to the current genotyping arrays for genome wide association studies, clinical trials, and in genome assessment of proliferating cancer cells.

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Pan-genomics in the human genome era

Cited by 239 publications

References 101 publications

Merqury: reference-free quality, completeness, and phasing assessment for genome assemblies

Merqury: reference-free quality, completeness, and phasing assessment for genome assemblies

Automated improvement of stickleback reference genome assemblies with Lep-Anchor software

Genome Diversity in Ukraine

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