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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
..., Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China 200438 ↵7 These authors contributed equally to this work. Corresponding author: hongliyan@smmu.edu.cnAbstractHepatitis B virus (HBV) integration is a key driver of hepatocellular carcinoma (HCC) occurrence and progression...
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Resource: Charting the regulatory landscape of TP53 on transposable elements in cancer
- Xuan Qu,
- Yonghao Liang,
- Colin McCornack,
- Xiaoyun Xing,
- Heather Schmidt,
- Chad Tomlinson,
- Catrina Fronick,
- Edward A. Belter, Jr.,
- Juan F. Macias-Velasco,
- and Ting Wang
Genome Res. June 2025 35: 1456-1471; Published in Advance May 13, 2025, doi:10.1101/gr.279398.124
..., rescuing WT TP53 expression allows for partial recovery of the TE expression profile observed in the context of chronic TP53 expression. TP53 mutations R175H and R273H manifest their oncogenic characteristic partially through activating TE promoters in a cell type–specific manner. Lastly, we identified...
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Research: Multisite long-read sequencing reveals the early contributions of somatic structural variations to HBV-related hepatocellular carcinoma tumorigenesis
- Tianfu Zeng,
- Haotian Liao,
- Lin Xia,
- Siyao You,
- Yanqun Huang,
- Jiaxun Zhang,
- Yahui Liu,
- Xuyan Liu,
- and Dan Xie
Genome Res. April 2025 35: 671-685; Published in Advance March 4, 2025, doi:10.1101/gr.279617.124
...↵3 These authors equally contributed to this work. Corresponding author: danxie@scu.edu.cnAbstractSomatic structural variations (SVs) represent a critical category of genomic mutations in hepatocellular carcinoma (HCC). However, the accurate identification of somatic SVs using short-read high...
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Research: Long-read RNA sequencing of archival tissues reveals novel genes and transcripts associated with clear cell renal cell carcinoma recurrence and immune evasion
- Joshua Lee,
- Elizabeth A. Snell,
- Joanne Brown,
- Charlotte E. Booth,
- Rosamonde E. Banks,
- Daniel J. Turner,
- Naveen S. Vasudev,
- and Dimitris Lagos
Genome Res. November 2024 34: 1849-1864; Published in Advance September 16, 2024, doi:10.1101/gr.278801.123
...disease recurrence, and identified the exhaustion marker TOX and the LINC04216 noncoding RNA as novel candidate recurrence-associated genes.Differential transcript usage analysis identifies candidate isoform switching events associated with ccRCC recurrenceOne of the advantages of the long-read sequencing...
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Method: The SeqSplice multiplexed minigene splicing assay for characterization and quantitation of variant-induced BRCA1 and BRCA2 splice isoforms
- Daffodil M. Canson,
- Michael T. Parsons,
- Gemma Moir-Meyer,
- Troy Dumenil,
- Gemma Montalban,
- Erica Lin,
- Terri P. McVeigh,
- Aimee L. Davidson,
- Shaun M. Bouckaert,
- Matt Trau,
- Darren Korbie,
- and Amanda B. Spurdle
Genome Res. September 2025 35: 2104-2115; Published in Advance August 6, 2025, doi:10.1101/gr.279557.124
...from a known BRCA1 exon 5 variant (c.188T>C) that produces a naturally occurring alternative isoform containing a 22 bp deletion (Δ5q22), in addition to the full-length (FL) transcript. As part of this experiment, we also assessed construction of SeqSplice libraries at different input concentrations...
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Research: Heterogeneous and novel transcript expression in single cells of patient-derived clear cell renal cell carcinoma organoids
- Tülay Karakulak,
- Natalia Zajac,
- Hella Anna Bolck,
- Anna Bratus-Neuenschwander,
- Qin Zhang,
- Weihong Qi,
- Debleena Basu,
- Tamara Carrasco Oltra,
- Hubert Rehrauer,
- Christian von Mering,
- Holger Moch,
- and Abdullah Kahraman
Genome Res. April 2025 35: 698-711; Published in Advance March 19, 2025, doi:10.1101/gr.279345.124
...and contributed equally to this work. Corresponding author: abdullah.kahraman@fhnw.chAbstractSplicing is often dysregulated in cancer, leading to alterations in the expression of canonical and alternatively spliced isoforms. We used the multiplexed arrays sequencing (MAS-seq) protocol of PacBio to sequence full...
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Research: Nucleosome binding by TP53, TP63, and TP73 is determined by the composition, accessibility, and helical orientation of their binding sites
- Patrick D. Wilson,
- Xinyang Yu,
- Christopher R. Handelmann,
- and Michael J. Buck
Genome Res. March 2025 35: 404-416; Published in Advance February 10, 2025, doi:10.1101/gr.279541.124
...and is mutated in >50% of human cancers (Joerger and Fersht 2007; Baugh et al. 2018; Marei et al. 2021). Upon activation by cell stress signals, TP53 induces the expression of genes involved in cell cycle arrest and apoptosis (Nguyen et al. 2018; Fischer and Sammons 2024). TP63 and TP73 also induce...
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Research: Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects of SF3B1 mutations
- Alicja Pacholewska,
- Matthias Lienhard,
- Mirko Brüggemann,
- Heike Hänel,
- Lorina Bilalli,
- Anja Königs,
- Felix Heß,
- Kerstin Becker,
- Karl Köhrer,
- Jesko Kaiser,
- Holger Gohlke,
- Norbert Gattermann,
- Michael Hallek,
- Carmen D. Herling,
- Julian König,
- Christina Grimm,
- Ralf Herwig,
- Kathi Zarnack,
- and Michal R. Schweiger
Genome Res. November 2024 34: 1832-1848; Published in Advance September 13, 2024, doi:10.1101/gr.279327.124
...Table S5). From these 15 tested, 12 (80%) clearly showed an increase in alternatively spliced isoform expression in the SF3B1mut/wt conditions. The strongest effects were observed for 3′AS events in MAP3K7, SEPTIN6, and SETD4, which showed an almost complete switch to the alternative splicing variant...
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Research: Deciphering the largest disease-associated transcript isoforms in the human neural retina with advanced long-read sequencing approaches
- Merel Stemerdink,
- Tabea Riepe,
- Nick Zomer,
- Renee Salz,
- Michael Kwint,
- Jaap Oostrik,
- Raoul Timmermans,
- Barbara Ferrari,
- Stefano Ferrari,
- Alfredo Dueñas Rey,
- Emma Delanote,
- Suzanne E. de Bruijn,
- Hannie Kremer,
- Susanne Roosing,
- Frauke Coppieters,
- Alexander Hoischen,
- Frans P.M. Cremers,
- Peter A.C. ‘t Hoen,
- Erwin van Wijk,
- and Erik de Vrieze
Genome Res. April 2025 35: 725-739; Published in Advance March 4, 2025, doi:10.1101/gr.280060.124
...contributing to the diversity of transcript isoforms expressed in the retina is alternative splicing, a biological process that allows a single gene to encode multiple transcript isoforms leading to tissue-specific differences in gene expression and function. This process involves the use of alternative...
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Method: Transcriptional fates of human-specific segmental duplications in brain
- Max L. Dougherty,
- Jason G. Underwood,
- Bradley J. Nelson,
- Elizabeth Tseng,
- Katherine M. Munson,
- Osnat Penn,
- Tomasz J. Nowakowski,
- Alex A. Pollen,
- and Evan E. Eichler
Genome Res. October 2018 28: 1566-1576; Published in Advance September 18, 2018, doi:10.1101/gr.237610.118
...genes whose promoters were included in the human-specific SD show expression patterns that are more similar to their ancestors than those that acquire it from new sequence.We took advantage of the full-length cDNA sequences to classify the consequences of the SD with respect to transcript or isoform...

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