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Access through your institution Buy or subscribe Pangenome graphs are commonly used as references for read mapping. To improve the mapping accuracy, Sirén et al. proposed a _k_-mer-based

approach for sampling haplotypes that were subsequently used to build a personalized subgraph. The original pangenome graph was partitioned into nonoverlapping blocks, and the local

haplotypes were labeled with graph-unique _k_-mers. Based on the _k_-mer counts in the reads, the authors were able to classify _k_-mers in the matrices as present (heterozygous or

homozygous) or absent, and select relevant haplotypes in each block accordingly. The sampled haplotypes led to construction of a personalized variation graph, which is actually a subgraph of

the original graph. The haplotype sampling approach is available as part of the vg toolkit and applied to pangenome graphs from the Human Pangenome Reference Consortium. Compared with a

frequency-filtered graph, the personalized subgraph with _k_-mer-based haplotype sampling is a superior reference for read mapping. It reduces genotyping errors and improves the accuracy in

calling small variants and genotyping structural variants, suggesting future directions of optimizing methods for personalizing pangenome references. ORIGINAL REFERENCE: _Nat. Methods_

https://doi.org/10.1038/s41592-024-02407-2 (2024) This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54

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AFFILIATIONS * Nature Genetics https://www.nature.com/ng Wei Li Authors * Wei Li View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR

Correspondence to Wei Li. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Li, W. Personalizing pangenome graphs with _k_-mers. _Nat Genet_ 56, 1999

(2024). https://doi.org/10.1038/s41588-024-01954-w Download citation * Published: 10 October 2024 * Issue Date: October 2024 * DOI: https://doi.org/10.1038/s41588-024-01954-w SHARE THIS

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