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Method: Long-read reconstruction of many diverse haplotypes with devider
- Jim Shaw,
- Christina Boucher,
- Yun William Yu,
- Noelle Noyes,
- and Heng Li
Genome Res. December 2025 35: 2637-2649; Published in Advance September 23, 2025, doi:10.1101/gr.280510.125
...then leverage the length of long reads by finding walks along the PDBG through unitig construction and read-to-graph alignment. We find that devider efficiently resolves haplotypes in a variety of synthetic and real data sets and show its versatility to reveal genomic heterogeneity.MethodsAt a high level...
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Method: Long-read RNA sequencing reveals allele-specific N⁶-methyladenosine modifications
- Dayea Park and
- Can Cenik
Genome Res. April 2025 35: 999-1011; Published in Advance October 29, 2024, doi:10.1101/gr.279270.124
...Dayea Park and Can Cenik Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA Corresponding author: ccenik@austin.utexas.eduAbstractLong-read sequencing technology enables highly accurate detection of allele-specific RNA expression, providing insights...
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Research: Strong bias in long-read sequencing prevents assembly of Drosophila melanogaster Y-linked genes
- A. Bernardo Carvalho,
- Bernard Y. Kim,
- and Fabiana Uno
Genome Res. January 2026 36: 71-82; Published in Advance October 1, 2025, doi:10.1101/gr.280604.125
...fails at multiple levels: read initiation (very few reads start within satellite regions), read elongation (satellite-containing reads are shorter on average), and basecalling (quality scores drop as sequencing enters a satellite sequence). These findings challenge the assumption that long-read...
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Research: Centromeric instability and chromoanasynthesis observed in nine supernumerary marker chromosomes resolved with long-read genome sequencing
- Kristine Bilgrav Saether,
- Angelo Salazar Mantero,
- Marlene Ek,
- Maria Pettersson,
- Elisabeth Syk Lundberg,
- Christopher M. Grochowski,
- Claudia M.B. Carvalho,
- Jesper Eisfeldt,
- and Anna Lindstrand
Genome Res. April 2026 36: 661-670; Published in Advance March 25, 2026, doi:10.1101/gr.281175.125
...resolution, as well as to identify their chromosomal origin and formation mechanism. Here, we apply long-read sequencing (lrGS) in combination with the telomere-to-telomere (T2T-CHM13) assembly to characterize the structure and genomic content of 10 clinically detected sSMCs. We use sequencing data...
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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
...alterations in transcriptomes or epis and cannot simultaneously capture genomic and epigenomic variations, which further hinders the phasing of methylation and the detection of allele-specific methylation (ASM).Addressing these challenges, long-read sequencing technologies, such as Pacific Biosciences (Pac...
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Research: Long-read sequencing reveals HBV integration patterns and oncogenic impact on early-onset hepatocellular carcinoma
- Yao Wang,
- Dong Yu,
- Yue Mei,
- ZhiDa Fu,
- Jian Lin,
- Di Wu,
- Yuan Yang,
- and Hongli Yan
Genome Res. November 2025 35: 2389-2405; Published in Advance September 16, 2025, doi:10.1101/gr.279889.124
...that integrates into host genomic DNA and forms virus–virus and virus–host genomic structural rearrangements, which are unstable and lead to further intratumoral heterogeneity and clonal evolution; through long-read sequencing, unique breakpoints shared across structural variants were also observed in HPV...
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Mini-Review: A Hitchhiker's Guide to long-read genomic analysis
- Medhat Mahmoud,
- Daniel P. Agustinho,
- and Fritz J. Sedlazeck
Genome Res. April 2025 35: 545-558; doi:10.1101/gr.279975.124
..., scalability, and accuracy advancements have driven this evolution. Concurrently, novel analytical methods have emerged to harness the full potential of long reads. These advancements have enabled milestones such as the first fully completed human , enhanced identification and understanding of complex genomic...
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Research: Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotypes and phenotypes in chronic lymphocytic leukemia
- Gage S. Black,
- Xiaomeng Huang,
- Yi Qiao,
- Philip Moos,
- Deepa Sampath,
- Deborah M. Stephens,
- Jennifer A. Woyach,
- and Gabor T. Marth
Genome Res. April 2025 35: 686-697; Published in Advance February 18, 2025, doi:10.1101/gr.279049.124
...by the long-read scRNA-seq data (Fig. 4; Supplemental Figs. 5 and 6). We illustrate such concordance in patient 1, where the WES data showed a linear pattern of subclonal evolution (Fig. 4A). To visualize this same pattern of evolution within the scRNA-seq samples, we created a genotype matrix plot showing...
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Perspective: The impact of long-read sequencing on human population-scale genomics
- Tobias Rausch,
- Tobias Marschall,
- and Jan O. Korbel
Genome Res. April 2025 35: 593-598; doi:10.1101/gr.280120.124
...to genetic variants (Cheung et al. 2023). DNA methylation patterns captured by long-read sequencing can help reveal the parent of origin of genetic variation extending to chromosome-length haplotypes, as well as detect parent-specific methylation patterns to help resolve genomic imprinting and disease...
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Method: De novo detection of somatic variants in high-quality long-read single-cell RNA sequencing data
- Arthur Dondi,
- Nico Borgsmüller,
- Pedro F. Ferreira,
- Brian J. Haas,
- Francis Jacob,
- Viola Heinzelmann-Schwarz,
- Tumor Profiler Consortium,
- and Niko Beerenwinkel
Genome Res. April 2025 35: 900-913; Published in Advance March 19, 2025, doi:10.1101/gr.279281.124
....beerenwinkel@bsse.ethz.chAbstractIn cancer, genetic and transcriptomic variations generate clonal heterogeneity, leading to treatment resistance. Long-read single-cell RNA sequencing (LR scRNA-seq) has the potential to detect genetic and transcriptomic variations simultaneously. Here, we present LongSom, a computational workflow leveraging...
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