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Pangenome graph construction from genome alignments with Minigraph-Cactus

Item Type:Article
Title:Pangenome graph construction from genome alignments with Minigraph-Cactus
Creators Name:Hickey, G. and Monlong, J. and Ebler, J. and Novak, A.M. and Eizenga, J.M. and Gao, Y. and Marschall, T. and Li, H. and Paten, B.
Abstract:Pangenome references address biases of reference genomes by storing a representative set of diverse haplotypes and their alignment, usually as a graph. Alternate alleles determined by variant callers can be used to construct pangenome graphs, but advances in long-read sequencing are leading to widely available, high-quality phased assemblies. Constructing a pangenome graph directly from assemblies, as opposed to variant calls, leverages the graph’s ability to represent variation at different scales. Here we present the Minigraph-Cactus pangenome pipeline, which creates pangenomes directly from whole-genome alignments, and demonstrate its ability to scale to 90 human haplotypes from the Human Pangenome Reference Consortium. The method builds graphs containing all forms of genetic variation while allowing use of current mapping and genotyping tools. We measure the effect of the quality and completeness of reference genomes used for analysis within the pangenomes and show that using the CHM13 reference from the Telomere-to-Telomere Consortium improves the accuracy of our methods. We also demonstrate construction of a Drosophila melanogaster pangenome.
Keywords:Alleles, DNA Sequence Analysis, Haplotypes, High-Throughput Nucleotide Sequencing, Human Genome, Animals, Drosophila melanogaster
Source:Nature Biotechnology
Publisher:Nature Publishing Group
Page Range:663-673
Date:April 2024
Additional Information:Ashley D. Sanders is a member of the Human Pangenome Reference Consortium.
Official Publication:https://doi.org/10.1038/s41587-023-01793-w
PubMed:View item in PubMed

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