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Method: Pangenome-based genome inference using integer programming
- Ghanshyam Chandra,
- Md Helal Hossen,
- Stephan Scholz,
- Alexander T. Dilthey,
- Daniel Gibney,
- and Chirag Jain
Genome Res. December 2025 35: 2661-2670; Published in Advance August 21, 2025, doi:10.1101/gr.280567.125
...(coverage 0.1×–10×). For these five samples, complete major histocompatibility complex (MHC) haplotype sequences have been previously determined using long-read assembly (Houwaart et al. 2023). As our pan reference, we used a haplotype-resolved pan directed acyclic graph (DAG) of 49 MHC haplotype sequences...
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Method: Strain-level metagenomic profiling using pangenome graphs with PanTax
- Wenhai Zhang,
- Yuansheng Liu,
- Guangyi Li,
- Jialu Xu,
- Enlian Chen,
- Alexander Schönhuth,
- and Xiao Luo
Genome Res. February 2026 36: 405-420; Published in Advance January 14, 2026, doi:10.1101/gr.280858.125
...and horizontal gene transfer in microorganisms may result in different strains of the same species, which further increases the biological diversity and complexity of microbial communities. Diversity of microbial communities at the level of strains is a key factor in microbiome-related research, as it does...
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Research: Pangenome analysis reveals families of ubiquitin-ligase adaptors as key genomic divergence drivers that lead to hybrid incompatibility
- Dongying Xie,
- Pohao Ye,
- Yiming Ma,
- and Zhongying Zhao
Genome Res. March 2026 36: 506-521; Published in Advance February 17, 2026, doi:10.1101/gr.280885.125
.... 2020; Jiao et al. 2025). These interactions often fuel hybrid genomic conflicts. Short-read sequencing technologies have struggled to resolve such complexities owing to inherent limitations in assembly. In contrast, the advent of long-read sequencing technologies, such as of Pacific Biosciences (Pac...
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Method: Full-resolution HLA and KIR gene annotations for human genome assemblies
- Ying Zhou,
- Li Song,
- and Heng Li
Genome Res. November 2024 34: 1931-1941; Published in Advance June 5, 2024, doi:10.1101/gr.278985.124
...haplotypes, including all the major MHC class II structures. HLA 102: 28–43. doi:10.1111/tan.15020 ↵Hung T-K, Liu W-C, Lai S-K, Chuang H-W, Lee Y-C, Lin H-Y, Hsu C-L, Chen C-Y, Yang Y-C, Hsu JS, et al. 2024. Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pan assemblies. Genome...
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Method: Accurate short-read alignment through r-index-based pangenome indexing
- Rahul Varki,
- Massimiliano Rossi,
- Eddie Ferro,
- Marco Oliva,
- Erik Garrison,
- Ben Langmead,
- and Christina Boucher
Genome Res. July 2025 35: 1609-1620; Published in Advance June 12, 2025, doi:10.1101/gr.279858.124
...we constructed using the maternal and paternal haplotype-resolved assemblies of the 47 individuals included in the HPRC year 1, version 2 data freeze (https://human-pangenomics.s3.amazonaws.com/index.html) in addition to T2T-CHM13 (https://github.com/marbl/CHM13) and GRCh38. To construct the pan...
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Research: Lake Malawi cichlid pangenome graph reveals extensive structural variation driven by transposable elements
- Fu Xiang Quah,
- Miguel Vasconcelos Almeida,
- Moritz Blumer,
- Chengwei Ulrika Yuan,
- Bettina Fischer,
- Kirsten See,
- Ben Jackson,
- Richard Zatha,
- Bosco Rusuwa,
- George F. Turner,
- M. Emília Santos,
- Hannes Svardal,
- Martin Hemberg,
- Richard Durbin,
- and Eric Miska
Genome Res. May 2025 35: 1094-1107; Published in Advance April 10, 2025, doi:10.1101/gr.279674.124
...-read assemblies of Lake Malawi haplochromine cichlids. This graph intuitively represents complex and nested variation between the s and reveals that the SV landscape is dominated by large insertions, many exclusive to individual assemblies. The graph incorporates a substantial amount of extra sequence across...
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Method: Taurine pangenome uncovers a segmental duplication upstream of KIT associated with depigmentation in white-headed cattle
- Sotiria Milia,
- Alexander S. Leonard,
- Xena Marie Mapel,
- Sandra Milena Bernal Ulloa,
- Cord Drögemüller,
- and Hubert Pausch
Genome Res. April 2025 35: 1041-1052; Published in Advance December 18, 2024, doi:10.1101/gr.279064.124
...assembly path similarities within the graph to reveal an association between two most likely serial alleles of a complex structural variant (SV) 66 kb upstream of KIT and facial depigmentation. The complex SV contains a variable number of tandemly duplicated 14.3 kb repeats, consisting of LTRs, LINEs...
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Method: Interactive visualization and interpretation of pangenome graphs by linear reference–based coordinate projection and annotation integration
- Zepu Miao and
- Jia-Xing Yue
Genome Res. February 2025 35: 296-310; Published in Advance January 13, 2025, doi:10.1101/gr.279461.124
..., the GRCh38 shows a simple linear path as expected. The CHM13 T2T assembly, on the other hand, shows the characteristic S-shaped pattern in both the Minigraph and Minigraph-Cactus pan graphs for the inverted region. In the PGGB graph, the pattern is more complex, likely owing to the sequence collapsing...
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Method: Haplotype-aware sequence alignment to pangenome graphs
- Ghanshyam Chandra,
- Daniel Gibney,
- and Chirag Jain
Genome Res. September 2024 34: 1265-1275; Published in Advance July 16, 2024, doi:10.1101/gr.279143.124
...75080, USA Corresponding author: chirag@iisc.ac.inAbstractModern pan graphs are built using haplotype-resolved assemblies. When mapping reads to a pan graph, prioritizing alignments that are consistent with the known haplotypes improves genotyping accuracy. However, the existing rigorous formulations...
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Perspective: Unraveling the hidden complexity of cancer through long-read sequencing
- Qiuhui Li,
- Ayse G. Keskus,
- Justin Wagner,
- Michal B. Izydorczyk,
- Winston Timp,
- Fritz J. Sedlazeck,
- Alison P. Klein,
- Justin M. Zook,
- Mikhail Kolmogorov,
- and Michael C. Schatz
Genome Res. April 2025 35: 599-620; Published in Advance March 20, 2025, doi:10.1101/gr.280041.124
...excluded from variant benchmarks even with near-perfect assemblies due to challenges in aligning, representing, and comparing large complex SVs around segmental duplications and satellite repeats.View larger version: In this window In a new window Figure 2. Comparative analysis of structural variation...
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