Pangenomics enables genotyping of known structural variants in 5202 diverse genomes
Jouni Sirén, Jean Monlong, Xian Chang, Adam M. Novak, Jordan M. Eizenga, Charles Markello, Jonas A. Sibbesen, Glenn Hickey, Pi-Chuan Chang, Andrew Carroll, Namrata Gupta, Stacey Gabriel, Thomas W. Blackwell, Aakrosh Ratan, Kent D. Taylor, Stephen S. Rich, Jerome I. Rotter, David Haussler, Erik Garrison, Benedict Paten
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.