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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
.... Originally developed from bacterial studies aimed at understanding the complete genetic diversity of bacterial genes, the concept of the pan has been expanded to encompass the full genomic variation within any biological population (Golicz et al. 2020; Abondio et al. 2023). Because of lower sequencing costs...
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Resource: Multitissue single-nucleus RNA-seq reveals cell type–specific regulatory patterns of alternative polyadenylation in pigs
- Qiuhan Wen,
- Zhen Wang,
- Qi Bao,
- Tianli Ding,
- Haihan Zhang,
- Jianbo Li,
- Zhuang Liu,
- Jieping Huang,
- and Guoqiang Yi
Genome Res. September 2025 35: 2116-2129; Published in Advance June 16, 2025, doi:10.1101/gr.280095.124
...-cell atlas of pigs by adding a layer of posttranscriptional regulation to the existing gene expression data, highlighting the significant role of cell type–specific 3′ UTR lengths in cell commitment and complex trait regulation.Alternative polyadenylation (APA) refers to the process by which pre-mRNA adds...
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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
.... 2007; Turpin et al. 2016). Thus, a deeper understanding of these resistance mechanisms remains a critical challenge in overcoming and managing breast cancer tumors expressing HER2.Alternative splicing, a fundamental post-transcriptional process in eukaryotic gene expression, allows a single gene locus...
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RECOMB 2022 Special/Methods: Lossless indexing with counting de Bruijn graphs
- Mikhail Karasikov,
- Harun Mustafa,
- Gunnar Rätsch,
- and André Kahles
Genome Res. September 2022 32: 1754-1764; Published in Advance May 24, 2022, doi:10.1101/gr.276607.122
...attributes such as gene expression or positions in a general manner have remained underexplored. In this work, we propose counting de Bruijn graphs, a notion generalizing annotated de Bruijn graphs by supplementing each node–label relation with one or many attributes (e.g., a k-mer count or its positions...
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Method: Highly efficient and scarless genome editing via essential gene-coupled homology-directed repair
- Joo Hye Yeo,
- Hyongbum Henry Kim,
- Sang Ho Oh,
- and Jinu Lee
Genome Res. April 15, 2026 gr.281194.125; Published in Advance April 15, 2026, doi:10.1101/gr.281194.125
...strategies, including small-molecule treatments and marker-based 32 selection, are constrained by cytotoxicity, genomic scarring, and inconsistent 33 performance. Here, we present ESS-HDR (essential gene–supported scarless HDR), a 34 robust, drug- and marker-free platform that selectively enriches HDR...
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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
...beads. To focus on individual candidate genes predicted to be bound by the protein of interest, precipitated DNA can be analyzed using qPCR with primers designed specifically against the regulatory sequences of the GOIs. Alternatively, in ChIP-seq following precipitation, cross-links are reversed...
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Method: Joint imputation and deconvolution of gene expression across spatial transcriptomics platforms
- Hongyu Zheng,
- Hirak Sarkar,
- and Benjamin J. Raphael
Genome Res. December 2025 35: 2734-2743; Published in Advance November 17, 2025, doi:10.1101/gr.280555.125
...techniques to measure gene expression in physical space with varying spatial resolution, gene panel size, sequencing depth, processing time, and cost. Selecting the most appropriate SRT protocol for profiling a target sample can be challenging. One alternative is to use multiple SRT methods to profile...
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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
...of absolute elongation rates in kb/min.Alternative indirect approaches, such as the elongation indexes derived from the ratio of TT-seq to RNAPII occupancy (e.g., from mNET-seq or PRO-seq), have been used to infer elongation velocity along the gene body (Gressel et al. 2017; Caizzi et al. 2021; Mimoso...
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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
...). Differential analysis was performed using a paired two-tailed DESeq2 test. (C,D) Gene Ontology enrichment analysis for differentially expressed genes increasing (C) or decreasing (D) in expression. Select terms are displayed. (E) The top five unique TF motifs for repressed or activated ATAC peaks. (F...
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Method: Reference-informed prediction of alternative splicing and splicing-altering mutations from sequences
- Chencheng Xu,
- Suying Bao,
- Ye Wang,
- Wenxing Li,
- Hao Chen,
- Yufeng Shen,
- Tao Jiang,
- and Chaolin Zhang
Genome Res. July 2024 34: 1052-1065; Published in Advance July 26, 2024, doi:10.1101/gr.279044.124
..., Terrytown, NY 10591, USA; 9Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA Corresponding authors: jiang@cs.ucr.edu, cz2294@columbia.eduAbstractAlternative splicing plays a crucial role in protein diversity and gene expression regulation...
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