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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
...isoforms from the same gene increases vastly the complexity of the transcriptome and proteome in eukaryotes (Keren et al. 2010; Nilsen and Graveley 2010). Alternative isoforms with different coding sequences can be generated through multiple types of alternative splicing (AS) events (Naftaly et al. 2021...
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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
..., and translation efficiency. In contrast, ALE-APA results from multiple PASs located in alternative terminal exons, which could lead to the production of truncated protein isoforms (Mariella et al. 2019; Goering et al. 2021). These alternatively polyadenylated mRNAs greatly expand the diversity of transcripts...
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Research: Resolving complex duplication variants in autism spectrum disorder using long-read genome sequencing
- Jesper Eisfeldt,
- Edward J. Higginbotham,
- Felix Lenner,
- Jennifer Howe,
- Bridget A. Fernandez,
- Anna Lindstrand,
- Stephen W. Scherer,
- and Lars Feuk
Genome Res. November 2024 34: 1763-1773; Published in Advance October 29, 2024, doi:10.1101/gr.279263.124
...involving duplications which had been identified by srGS, but where the architecture of the genomic rearrangement and breakpoints could not be fully elucidated from srGS data (Trost et al. 2022). Using ONT lrGS, we resolve the CGRs structure and study the effects on methylation patterns to unravel both...
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Method: Resolving the chromatin impact of mosaic variants with targeted Fiber-seq
- Stephanie C. Bohaczuk,
- Zachary J. Amador,
- Chang Li,
- Benjamin J. Mallory,
- Elliott G. Swanson,
- Jane Ranchalis,
- Mitchell R. Vollger,
- Katherine M. Munson,
- Tom Walsh,
- Morgan O. Hamm,
- Yizi Mao,
- Andre Lieber,
- and Andrew B. Stergachis
Genome Res. December 2024 34: 2269-2278; Published in Advance December 9, 2024, doi:10.1101/gr.279747.124
...of an internal nucleosome varied across the individual reads (Fig. 1F), indicating that the precise pattern of accessibility within a promoter can vary quite substantially from fiber to fiber.Given the potential for targeted Fiber-seq to synchronously resolve alterations in both the and chromatin epi at single...
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Method: Statistically rigorous and computationally efficient chromatin stripe detection with Quagga
- Fan Feng,
- Sean Moran,
- Anders S. Hansen,
- Xiaotian Zhang,
- and Jie Liu
Genome Res. January 2026 36: 159-168; Published in Advance November 12, 2025, doi:10.1101/gr.280132.124
...regulation, and cell differentiation. Nevertheless, StripeDiff does not provide a user-friendly package to directly call all stripes with common contact map files.Here we introduce Quagga, a statistically rigorous, algorithmically efficient, and interpretable tool to identify stripes. Quagga's biggest...
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Method: Robust and efficient annotation of cell states through gene signature scoring
- Laure Ciernik,
- Agnieszka Kraft,
- Florian Barkmann,
- Josephine Yates,
- and Valentina Boeva
Genome Res. March 2026 36: 630-644; Published in Advance February 18, 2026, doi:10.1101/gr.280926.125
...phenotype (Nevins and Potti 2007). One key application of signature scoring is cell annotation, as it offers a highly efficient and reliable method for classifying cells into types and states (Neftel et al. 2019). Notably, the quality of gene signatures plays a critical role in this process, as the accuracy...
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Research: Assessing the readiness of Oxford Nanopore sequencing for clinical genomics applications
- Judith Arres,
- Santosh Elavalli,
- Shalini Behl,
- Daniel Matias Sanchez,
- Ayesha Al Ali,
- Abdelrahman Ahmed Yehia Abdelaziz Saad,
- Azza Attia,
- Cyla Minas,
- Sharika Pariyachery,
- Shariq Ahmed,
- Fatmah Aldhuhoori,
- Nitu Thulasidharan,
- Gurunath Katagi,
- Omar Soliman,
- Shilp Purohit,
- Vinay Kusuma,
- Raony Cardenas,
- Thyago Cardoso,
- Luis F. Paulin,
- Philippe Sanio,
- Joseph Mafofo,
- Haiguo Wu,
- Val Zvereff,
- Albarah El-Khani,
- Fahed Al Marzooqi,
- Tiago R. Magalhães,
- Fritz J. Sedlazeck,
- and Javier Quilez
Genome Res. March 2026 36: 460-471; Published in Advance February 11, 2026, doi:10.1101/gr.280134.124
...annotation for a cystic fibrosis–causing indel in GM07829. This work underscores the growing readiness of ONT for clinical applications, highlighting both its advancements and its potential for broader adoption in clinical genomics and large-scale operations.The advent of long-read sequencing (LRS) enabled...
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Method: MCHelper automatically curates transposable element libraries across eukaryotic species
- Simon Orozco-Arias,
- Pío Sierra,
- Richard Durbin,
- and Josefa González
Genome Res. December 2024 34: 2256-2268; Published in Advance December 9, 2024, doi:10.1101/gr.278821.123
..., there are several automatic tools available that allow de novo discovery and annotation of TE insertions, e.g., RepeatModeler2 (RM2) (Flynn et al. 2020), REPET (Flutre et al. 2011), and EDTA (Ou et al. 2019) (for a more comprehensive list visit: https://tehub.org/) (Elliott et al. 2021). However, libraries produced...
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Method: Efficient integration of spatial omics data for joint domain detection, matching, and alignment with stMSA
- Han Shu,
- Jing Chen,
- Chang Xu,
- Jialu Hu,
- Yongtian Wang,
- Jiajie Peng,
- Qinghua Jiang,
- Xuequn Shang,
- and Tao Wang
Genome Res. October 2025 35: 2285-2299; Published in Advance August 14, 2025, doi:10.1101/gr.280584.125
...of surface protein expression using specific antibodies, thereby enriching transcriptomic data with valuable spatially resolved proteomic information. This integration allows for a comprehensive understanding of the spatial distribution of proteins, offering invaluable insights into the proteomic landscape...
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Research: Meta-analysis of activated neurons reveals dynamic regulation of diverse classes of alternative splicing
- Keegan S. Krick,
- Marissa Maroni,
- Erica Korb,
- Kristen W. Lynch,
- and Elizabeth A. Heller
Genome Res. June 2025 35: 1301-1312; Published in Advance April 24, 2025, doi:10.1101/gr.280082.124
...that are not differentially expressed after KCl treatment. Functionally, alternative splicing of RNA processing machinery and regulators precedes splicing of genes related to neuronal function. Given recent advances in elucidating chromatin-mediated alternative splicing in the brain, we explored the coincident regulation...

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