Defining and cataloging variants in pangenome graphs.

Authors

Pouria Salehi Nowbandegani, Shenghan Zhang, Haoyang Hu, Heng Li, Luke J O'Connor

Published in

Cell genomics. Pages 101327. Aug 17, 2026. Epub Aug 17, 2026.

Abstract

Structural variation causes some human haplotypes to align poorly with the linear reference genome, and this leads to "reference bias." A pangenome reference graph could ameliorate this bias by relating a sample to multiple reference assemblies. However, this approach requires a new definition of a "genetic variant." We define pangenome variants against a reference tree that includes all nodes (sequences) of the pangenome graph but only a subset of its edges; non-reference edges are variant edges. Analyzing the Minigraph-Cactus draft human pangenome reference graph, we identified 29.6 million genetic variants. 3.5 million variants (11.7%) have a reference allele that is not on GRCh38; these variants are difficult to detect without a pangenome reference and are found within tangled, multiallelic regions. We analyze the HLA-A and RHD gene regions and identify thousands of small variants entangled with several structural variants. We release the open-source pantree and a variant call format (VCF) variant catalog.

PMID:
42607688
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.