Pangenomics enables genotyping of known structural variants in 5202 diverse genomes

Science. 2021 Dec 17;374(6574):abg8871. doi: 10.1126/science.abg8871. Epub 2021 Dec 17.

Abstract

We introduce Giraffe, a pangenome short-read mapper that can efficiently map to a collection of haplotypes threaded through a sequence graph. Giraffe maps sequencing reads to thousands of human genomes at a speed comparable to that of standard methods mapping to a single reference genome. The increased mapping accuracy enables downstream improvements in genome-wide genotyping pipelines for both small variants and larger structural variants. We used Giraffe to genotype 167,000 structural variants, discovered in long-read studies, in 5202 diverse human genomes that were sequenced using short reads. We conclude that pangenomics facilitates a more comprehensive characterization of variation and, as a result, has the potential to improve many genomic analyses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Alleles
  • Computational Biology
  • Genetic Variation*
  • Genome, Fungal
  • Genome, Human*
  • Genomics / methods*
  • Genotype
  • Genotyping Techniques*
  • Haplotypes
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Saccharomyces / genetics
  • Saccharomyces cerevisiae / genetics
  • Sequence Analysis, DNA

Supplementary concepts

  • Saccharomyces paradoxus

Grants and funding