*Result*: Compressive pangenomics using mutation-annotated networks.
Title:
Compressive pangenomics using mutation-annotated networks.
Authors:
Walia S; Department of Electrical and Computer Engineering, University of California, San Diego, San Diego, CA, USA., Motwani H; Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA, USA., Tseng YH; Department of Electrical and Computer Engineering, University of California, San Diego, San Diego, CA, USA., Smith K; Department of Electrical and Computer Engineering, University of California, San Diego, San Diego, CA, USA., Corbett-Detig R; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, USA., Turakhia Y; Department of Electrical and Computer Engineering, University of California, San Diego, San Diego, CA, USA. yturakhia@ucsd.edu.
Source:
Nature genetics [Nat Genet] 2026 Feb; Vol. 58 (2), pp. 445-453. Date of Electronic Publication: 2026 Jan 12.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE
Imprint Name(s):
Original Publication: New York, NY : Nature Pub. Co., c1992-
MeSH Terms:
References:
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Deorowicz, S., Danek, A. & Li, H. AGC: compact representation of assembled genomes with fast queries and updates. Bioinformatics 39, btad097 (2023). (PMID: 36864624999479110.1093/bioinformatics/btad097)
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Turakhia, Y. et al. Ultrafast sample placement on existing tRees (UShER) enables real-time phylogenetics for the SARS-CoV-2 pandemic. Nat. Genet. 53, 809–816 (2021). (PMID: 33972780924829410.1038/s41588-021-00862-7)
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Ondov, B. D. et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol. 17, 132 (2016). (PMID: 27323842491504510.1186/s13059-016-0997-x)
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Chen, Z. et al. Global landscape of SARS-CoV-2 genomic surveillance and data sharing. Nat. Genet. 54, 499–507 (2022). (PMID: 35347305900535010.1038/s41588-022-01033-y)
Bloom, J. D., Beichman, A. C., Neher, R. A. & Harris, K. Evolution of the SARS-CoV-2 mutational spectrum. Mol. Biol. Evol. 40, msad085 (2023). (PMID: 370395571012487010.1093/molbev/msad085)
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Grant Information:
75D30123C17463 U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC); Amazon Research Award Amazon Web Services (AWS); U01HG013755 U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI); AMD AI & HPC fund Advanced Micro Devices (AMD); R35GM128932 U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
Entry Date(s):
Date Created: 20260112 Date Completed: 20260212 Latest Revision: 20260213
Update Code:
20260213
DOI:
10.1038/s41588-025-02478-7
PMID:
41526696
Database:
MEDLINE
*Further Information*
*Pangenomics is an emerging field that uses collections of genomes, rather than a single reference, to reduce bias and capture intra-species diversity. However, existing pangenomic data formats face challenges in scaling to millions of genomes and primarily emphasize variation, often neglecting the underlying mutational events and evolutionary relationships. This work introduces Pangenome Mutation-Annotated Network (PanMAN), a lossless pangenome representation that achieves compression ratios ranging from 3.5-1,391× in file sizes compared to existing variation-preserving formats, with performance generally improving on larger datasets. In addition to compression, PanMAN increases representational capacity by encoding detailed mutational and evolutionary histories inferred across genomes, thereby enabling new biological insights. Using PanMAN, a comprehensive SARS-CoV-2 pangenome was constructed from 8 million publicly available sequences, requiring only 366 MB of disk space. We also present 'panmanUtils', a toolkit that supports common analyses and ensures interoperability with existing software. PanMAN is poised to greatly improve the scale, speed, resolution and scope of pangenomic analysis and data sharing.
(© 2026. The Author(s), under exclusive licence to Springer Nature America, Inc.)*
*Competing interests: All authors declare no competing interests.*