We often talk about pangenome reference but what does "reference" mean? If it means the whole graph, what is a variant? My collaborators Pouria and Luke give a clean answer: the reference is a spanning tree including GRCh38 and variants are leftover edges. See preprint for more.

Luke O'Connor

@luke0connor · Twitter · 2025-08-07 13:27 UTC

New preprint on a surprising question - with a pangenome reference, *what is a genetic variant?* https://www.biorxiv.org/content/10.1101/2025.08.04.668502v1 With Pouria Salehi Nowbandani, Shenghan Zhang, Haoyang Hu, and Heng Li @lh3lh3