Pangenome graph construction from genome alignments with Minigraph-Cactus
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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.
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Building assembly graphs rather than using single reference genomes is now routine with mature tools and advancements in genome assembly.
“Building assembly graphs rather than using single reference genomes is now routine with mature tools and advancements in genome assembly ( 207 )”
From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [207]
The Abstract says advances in long-read sequencing are making high-quality assemblies widely available, and the paper presents a tool for constructing pangenome graphs from them. But the Discussion says graph construction remains an active research area and predicts that producing large numbers of high-quality genomes will soon be routine; it does not say that building assembly graphs is already routine. The supplied passages have section labels but no page numbers. (LLM, conf=0.86)
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Sorted by citations
A draft human pangenome reference.
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Self-citationGBZ file format for pangenome graphs
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- Authors
- Hickey, G., Monlong, J., Ebler, J., Novak, A. M., Eizenga, J. M., Gao, Y., Human Pangenome Reference Consortium, Abel, H. J., Antonacci-Fulton, L. L., Asri, M., Baid, G., Baker, C. A., Belyaeva, A., Billis, K., Bourque, G., Buonaiuto, S., Carroll, A., Chaisson, M. J. P., Chang, P.-C., Chang, X. H., Cheng, H., Chu, J., Cody, S., Colonna, V., Cook, D. E., Cook-Deegan, R. M., Cornejo, O. E., Diekhans, M., Doerr, D., Ebert, P., Ebler, J., Eichler, E. E., Fairley, S., Fedrigo, O., Felsenfeld, A. L., Feng, X., Fischer, C., Flicek, P., Formenti, G., Frankish, A., Fulton, R. S., Garg, S., Garrison, E., Garrison, N. A., Giron, C. G., Green, R. E., Groza, C., Guarracino, A., Haggerty, L., Hall, I. M., Harvey, W. T., Haukness, M., Haussler, D., Heumos, S., Hoekzema, K., Hourlier, T., Howe, K., Jain, M., Jarvis, E. D., Ji, H. P., Kenny, E. E., Koenig, B. A., Kolesnikov, A., Korbel, J. O., Kordosky, J., Koren, S., Lee, H., Lewis, A. P., Liao, W.-W., Lu, S., Lu, T.-Y., Lucas, J. K., Magalhães, H., Marco-Sola, S., Marijon, P., Markello, C., Marschall, T., Martin, F. J., McCartney, A., McDaniel, J., Miga, K. H., Mitchell, M. W., Mountcastle, J., Munson, K. M., Mwaniki, M. N., Nattestad, M., Nurk, S., Olsen, H. E., Olson, N. D., Pesout, T., Phillippy, A. M., Popejoy, A. B., Porubsky, D., Prins, P., Puiu, D., Rautiainen, M., Regier, A. A., Rhie, A., Sacco, S., Sanders, A. D., Schneider, V. A., Schultz, B. I., Shafin, K., Sibbesen, J. A., Sirén, J., Smith, M. W., Sofia, H. J., Tayoun, A. N. A., Thibaud-Nissen, F., Tomlinson, C., Tricomi, F. F., Villani, F., Vollger, M. R., Wagner, J., Walenz, B., Wang, T., Wood, J. M. D., Zimin, A. V., Zook, J. M., Marschall, T., Li, H., & Paten, B.
- Affiliations
- University of California, Santa Cruz (US)
- Children's Hospital of Philadelphia (US)
- Washington University in St. Louis (US)
- Google (United States) (US)
- University of Washington (US)
- European Bioinformatics Institute (GB)
- Kyoto University (JP)
- Institute of Genetics and Biophysics (IT)
- University of Southern California (US)
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
- University of Tennessee Health Science Center (US)
- Washington Center (US)
- Heinrich Heine University Düsseldorf (DE)
- Howard Hughes Medical Institute (US)
- Rockefeller University (US)
- National Institutes of Health (US)
- Novo Nordisk Foundation (DK)
- University of California, Los Angeles (US)
- McGill University (CA)
- Yale University (US)
- Quantitative Biology Center (DE)
- Wellcome Sanger Institute (GB)
- Northeastern University (US)
- Stanford Medicine (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of California, San Francisco (US)
- National Institute of Standards and Technology (US)
- Coriell Institute For Medical Research (US)
- University of Pisa (IT)
- University of California, Davis (US)
- Johns Hopkins University (US)
- Max Delbrück Center (DE)
- University of Copenhagen (DK)
- Al Jalila Foundation (AE)
- Corresponding author
- Hickey, Glenn
- Paten, Benedict
- ORCID
- Hickey, Glenn
- Monlong, Jean
- Novak, Adam M.
- Eizenga, Jordan M.
- Gao, Yan
- Abel, Haley J.
- Asri, Mobin
- Baid, Gunjan
- Belyaeva, Anastasiya
- Billis, Konstantinos
- Bourque, Guillaume
- Buonaiuto, Silvia
- Carroll, Andrew
- Chaisson, Mark J. P.
- Chang, Pi-Chuan
- Chang, Xian H.
- Cheng, Haoyu
- Chu, Justin
- Colonna, Vincenza
- Cook, Daniel E.
- Cook-Deegan, Robert M.
- Cornejo, Omar E.
- Diekhans, Mark
- Doerr, Daniel
- Ebert, Peter
- Eichler, Evan E.
- Fairley, Susan
- Fedrigo, Olivier
- Feng, Xiaowen
- Flicek, Paul
- Formenti, Giulio
- Frankish, Adam
- Fulton, Robert S.
- Garg, Shilpa
- Garrison, Erik
- Garrison, Nanibaa’ A.
- Green, Richard E.
- Groza, Cristian
- Guarracino, Andrea
- Haggerty, Leanne
- Hall, Ira M.
- Harvey, William T.
- Haukness, Marina
- Haussler, David
- Heumos, Simon
- Hoekzema, Kendra
- Hourlier, Thibaut
- Howe, Kerstin
- Jain, Miten
- Jarvis, Erich D.
- Ji, Hanlee P.
- Kenny, Eimear E.
- Koenig, Barbara A.
- Kolesnikov, Alexey
- Korbel, Jan O.
- Koren, Sergey
- Lee, HoJoon
- Lewis, Alexandra P.
- Liao, Wen-Wei
- Lu, Shuangjia
- Lu, Tsung-Yu
- Lucas, Julian K.
- Magalhães, Hugo
- Marijon, Pierre
- Markello, Charles
- Martin, Fergal J.
- McDaniel, Jennifer
- Miga, Karen H.
- Mitchell, Matthew W.
- Mountcastle, Jacquelyn
- Munson, Katherine M.
- Mwaniki, Moses Njagi
- Nattestad, Maria
- Nurk, Sergey
- Olsen, Hugh E.
- Olson, Nathan D.
- Pesout, Trevor
- Phillippy, Adam M.
- Popejoy, Alice B.
- Prins, Pjotr
- Puiu, Daniela
- Rautiainen, Mikko
- Regier, Allison A.
- Rhie, Arang
- Sacco, Samuel
- Sanders, Ashley D.
- Shafin, Kishwar
- Sibbesen, Jonas A.
- Sirén, Jouni
- Smith, Michael W.
- Sofia, Heidi J.
- Tayoun, Ahmad N. Abou
- Tomlinson, Chad
- Tricomi, Francesca Floriana
- Villani, Flavia
- Vollger, Mitchell R.
- Wagner, Justin
- Walenz, Brian
- Wang, Ting
- Wood, Jonathan M. D.
- Zimin, Aleksey V.
- Zook, Justin M.
- Li, Heng
- Paten, Benedict
- Venue
- Nature Biotechnology
- Published
- 2023-05-10
- Volume
- 42
- Issue
- 4
- Pages
- 663-673
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC10638906
- OpenAlex
- W4376118380
- Cited by
- 343
- References
- 14
- Citations by year
- 2026: 140 · 2025: 105 · 2024: 72 · 2023: 24 · 2022: 1 · 2012: 1
- FWCI
- 30.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- www.nature.com
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- HAL (submittedVersion)
- Funders
- Heinrich-Heine-Universität Düsseldorf
- National Institutes of Health (OT2OD033761)
- High Performance Research Computing, Texas A and M University
- National Heart, Lung, and Blood Institute (OT3HL142481)
- National Human Genome Research Institute (R01HG010485, U01HG010973, U01HG010963, U01HG010971, R01HG011274, U01HG010961, R01HG010040, U24HG011853, U24HG007234, U24HG010262)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Physical Sciences › Computer Science › Artificial Intelligence › Algorithms and Data Compression
- Keywords
- pangenome graphs, whole-genome alignment, Human Pangenome Reference Consortium, reference genome bias
- MeSH terms
- Alleles, Animals, Drosophila melanogaster, Haplotypes, Humans, Genome, Human, Sequence Analysis, DNA, High-Throughput Nucleotide Sequencing
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