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Research: Xist upstream deletion leads to dysregulation of Xist and autosomal gene expression
- Sudeshna Majumdar,
- Lakshmi Sowjanya Bammidi,
- Hemant C. Naik,
- Avinchal Manhas,
- Runumi Baro,
- Akash Kalita,
- Amlan Jyoti Naskar,
- Sundarraj Nidharshan,
- Girija S. Bariha,
- Dimple Notani,
- and Srimonta Gayen
Genome Res. September 2025 35: 1992-2010; Published in Advance August 6, 2025, doi:10.1101/gr.279822.124
...). From a viewpoint near the Xist transcriptional start sites, we found major contacts of the Xist with the regions encompassing Ftx loci on the inactive X in XEN cells (Fig. 1C). These interactions were found to be less in the active X Chromosome; however, we observed that Xist interacts at the 3′ region...
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Method: Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes
- Hongke Peng,
- Jafar S. Jabbari,
- Luyi Tian,
- Changqing Wang,
- Yupei You,
- Chong Chyn Chua,
- Natasha S. Anstee,
- Noorul Amin,
- Andrew H. Wei,
- Nadia M. Davidson,
- Andrew W. Roberts,
- David C.S. Huang,
- Matthew E. Ritchie,
- and Rachel Thijssen
Genome Res. April 2025 35: 942-955; Published in Advance January 10, 2025, doi:10.1101/gr.279322.124
...the transcriptome profile to isoform usage, mutations, and translocations in full-length transcripts at a single-cell level (Wu and Schmitz 2023).In recent years, several high-throughput methods have been developed to enable single-cell long-read sequencing. These approaches typically involve barcoding of c...
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Method: Long-read Ribo-STAMP simultaneously measures transcription and translation with isoform resolution
- Pratibha Jagannatha,
- Alexandra T. Tankka,
- Daniel A. Lorenz,
- Tao Yu,
- Brian A. Yee,
- Kristopher W. Brannan,
- Cathy J. Zhou,
- Jason G. Underwood,
- and Gene W. Yeo
Genome Res. November 2024 34: 2012-2024; Published in Advance June 21, 2024, doi:10.1101/gr.279176.124
...Methodist Research Institute, Houston, TX 77030, USA Corresponding author: geneyeo@ucsd.eduAbstractTranscription and translation are intertwined processes in which mRNA isoforms are crucial intermediaries. However, methodological limitations in analyzing translation at the mRNA isoform level have left gaps...
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Research: Alternative splicing generates HER2 isoform diversity underlying antibody–drug conjugate resistance in breast cancer
- Gabriela D.A. Guardia,
- Carlos H. dos Anjos,
- Aline Rangel-Pozzo,
- Filipe F. dos Santos,
- Alexander Birbrair,
- Paula F. Asprino,
- Anamaria A. Camargo,
- and Pedro A.F. Galante
Genome Res. September 2025 35: 1942-1958; Published in Advance July 15, 2025, doi:10.1101/gr.280304.124
...-term efficacy. Addressing these obstacles is vital for enhancing therapeutic strategies and patient care. Alternative splicing, a post-transcriptional mechanism that enhances transcript diversity (isoforms), can produce proteins with varied functions, cellular localizations, or binding properties. Here, we...
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Method: Biosurfer for systematic tracking of regulatory mechanisms leading to protein isoform diversity
- Mayank Murali,
- Jamie Saquing,
- Senbao Lu,
- Ziyang Gao,
- Emily F. Watts,
- Ben Jordan,
- Zachary Peters Wakefield,
- Ana Fiszbein,
- David R. Cooper,
- Peter J. Castaldi,
- Dmitry Korkin,
- and Gloria M. Sheynkman
Genome Res. April 2025 35: 1012-1024; Published in Advance March 14, 2025, doi:10.1101/gr.279317.124
...the functionality of downstream protein products. We introduce Biosurfer, a computational approach for comparing protein isoforms, while systematically tracking the transcriptional, splicing, and translational variations that underlie differences in the sequences of the protein products. Using Biosurfer, we...
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...first approach the question of what regulates your GOI transcriptionally, you should start by compiling available information on chromatin landscape (especially regulatory region hallmarks) and TF binding from browsers (e.g., UCSC Genome Browser) and user-friendly databases (e.g., Harmonizome). For most...
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Method: Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution
- Qian Qin,
- Victoria Popic,
- Kirsty Wienand,
- Houlin Yu,
- Emily White,
- Akanksha Khorgade,
- Asa Shin,
- Christophe Georgescu,
- Catarina D. Campbell,
- Arthur Dondi,
- Niko Beerenwinkel,
- Francisca Vazquez,
- Aziz M. Al'Khafaji,
- and Brian J. Haas
Genome Res. April 2025 35: 967-986; Published in Advance March 14, 2025, doi:10.1101/gr.279200.124
...short-read sequences. Recent advances in long-read isoform sequencing enable the detection of fusion transcripts at unprecedented resolution in bulk and single-cell samples. Here, we developed a new computational tool, CTAT-LR-Fusion, to detect fusion transcripts from long-read RNA-seq with or without...
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Method: Kinetic measurement of gene-specific RNA polymerase II transcription elongation rates
- Haiyue Liu and
- Lea H. Gregersen
Genome Res. November 2025 35: 2550-2562; Published in Advance October 22, 2025, doi:10.1101/gr.280852.125
...Haiyue Liu and Lea H. Gregersen Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark Corresponding author: leag@sund.ku.dkAbstractTranscription is regulated at multiple levels, including initiation, elongation, and termination...
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Review: Understanding isoform expression by pairing long-read sequencing with single-cell and spatial transcriptomics
- Natan Belchikov,
- Justine Hsu,
- Xiang Jennie Li,
- Julien Jarroux,
- Wen Hu,
- Anoushka Joglekar,
- and Hagen U. Tilgner
Genome Res. November 2024 34: 1735-1746; doi:10.1101/gr.279640.124
...in kidney cancer (Shiau et al. 2023).Single-cell long-read RNA-seq has also proven valuable in understanding infectious diseases. The parasite Plasmodium vivax, one of the species that causes malaria, had been difficult to accurately profile transcriptionally with bulk methods because of the variety...
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Resource: Full-length RNA transcript sequencing traces brain isoform diversity in house mouse natural populations
- Wenyu Zhang,
- Anja Guenther,
- Yuanxiao Gao,
- Kristian Ullrich,
- Bruno Huettel,
- Aftab Ahmad,
- Lei Duan,
- Kaizong Wei,
- and Diethard Tautz
Genome Res. November 2024 34: 2118-2132; Published in Advance September 17, 2024, doi:10.1101/gr.279166.124
...the largest diversity of cell types with an overall transcript diversity only comparable to the testis (Bekpen et al. 2018), but with many more of these transcripts being likely to be functional in the brain compared to the testis, where there is a lot of expression due to a transcriptionally permissive...

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