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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
...polyadenylation (APA) plays a crucial role in gene regulation and phenotypic diversity. Whereas extensive studies have explored the global APA landscape using bulk RNA-seq data, in-depth analyses of APA events at the single-cell level remain limited—particularly in farm animals. In this study, we construct...
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Research: Chimeric mitochondrial RNA transcripts predict mitochondrial genome deletion mutations in mitochondrial genetic diseases and aging
- Amy R. Vandiver,
- Allen Herbst,
- Paul Stothard,
- and Jonathan Wanagat
Genome Res. January 2025 35: 55-65; Published in Advance November 27, 2024, doi:10.1101/gr.279072.124
...skeletal muscle from which we observed an increase in chimeric mtRNA associated with aging (PRJNA793055). When we compared each samples’ sum total of chimeric mtRNA transcripts for all rat samples to the global transcriptome, we identified 6104 differentially expressed genes associated with the chimeric mt...
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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
...examples of modified nucleotides include bromouridine, which can be immunoprecipitated by specific antibodies (global run-on assay) (Core and Lis 2008), or biotinylated cytosine, which can be bound to streptavidin-based binders (precision run-on assay) (Mahat et al. 2016). The resulting transcripts...
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Resource: The ggRibo single-gene viewer reveals insights into translatome and other nucleotide-resolution omics data
- Hsin-Yen Larry Wu,
- Isaiah D. Kaufman,
- and Polly Yingshan Hsu
Genome Res. September 2025 35: 2130-2142; Published in Advance July 22, 2025, doi:10.1101/gr.280480.125
...the mechanism of mRNA translation (Guydosh and Green 2014; Chothani et al. 2023; Wu et al. 2024a).Although several Ribo-seq software packages generate aggregate plots to examine 3 nt periodicity at a global level (Ji et al. 2015; Calviello et al. 2016, 2020; Zhang et al. 2017; Xiao et al. 2018; Choudhary et al...
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Research: Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
- Benjamin D. Umans and
- Yoav Gilad
Genome Res. August 2025 35: 1689-1700; Published in Advance June 2, 2025, doi:10.1101/gr.280219.124
...topic modeling, which reveals context-specific gene regulation linked to dynamic cellular processes and environmental responses, offering a deeper understanding of how gene regulation is modulated in the brain. These findings underscore the importance of genotype-environment interactions in genetic...
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Research: Alternative splicing modulated by genetic variants demonstrates accelerated evolution regulated by highly conserved proteins
- Yun-Hua Esther Hsiao,
- Jae Hoon Bahn,
- Xianzhi Lin,
- Tak-Ming Chan,
- Rena Wang,
- and Xinshu Xiao
Genome Res. April 2016 26: 440-450; Published in Advance February 17, 2016, doi:10.1101/gr.193359.115
...-nucleotide variants (SNVs) all demonstrated positive selection or accelerated evolution in primates. We predicted that GMAS SNVs often alter binding of splicing factors, with SRSF1 affecting the most GMAS events and demonstrating global allelic binding bias. However, in contrast to their GMAS targets, the predicted...
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Research: Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease
- Stephanie Y. Yang,
- Christina A. Castellani,
- Ryan J. Longchamps,
- Vamsee K. Pillalamarri,
- Brian O'Rourke,
- Eliseo Guallar,
- and Dan E. Arking
Genome Res. March 2021 31: 349-358; Published in Advance January 13, 2021, doi:10.1101/gr.269381.120
....1096/fj.04-3284com ↵The GTEx Consortium. 2013. The Genotype-Tissue Expression (GTEx) project. Nat Genet 45: 580–585. doi:10.1038/ng.2653 ↵Guantes R, Rastrojo A, Neves R, Lima A, Aguado B, Iborra FJ. 2015. Global variability in gene expression and alternative splicing is modulated by mitochondrial content...
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Resource: Quantitative RNA-seq meta-analysis of alternative exon usage in C. elegans
- Nicolas J. Tourasse,
- Jonathan R.M. Millet,
- and Denis Dupuy
Genome Res. December 2017 27: 2120-2128; Published in Advance October 31, 2017, doi:10.1101/gr.224626.117
..., there may be several predicted orthologs to the same C. elegans gene. A global and optimal pairwise alignment was computed according to the Needleman and Wunsch algorithm (Needleman and Wunsch 1970) between the full nucleotide sequence of each C. elegans gene and its ortholog(s) using the program “needle...
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Method: Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution
- Ryan O'Hara,
- Enzo Tedone,
- Andrew Ludlow,
- Ejun Huang,
- Beatrice Arosio,
- Daniela Mari,
- and Jerry W. Shay
Genome Res. November 2019 29: 1878-1888; Published in Advance September 23, 2019, doi:10.1101/gr.250480.119
...though the basis of any mechanism regulating mtDNA copy number remains a poorly understood phenomenon (Gammage and Frezza 2019), cellular mitochondrial content is believed to modulate global transcription (Guantes et al. 2015), but this is an area of interest that remains mostly unexplored...
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Research: Comparative analysis of alternative polyadenylation in S. cerevisiae and S. pombe
- Xiaochuan Liu,
- Mainul Hoque,
- Marc Larochelle,
- Jean-François Lemay,
- Nathan Yurko,
- James L. Manley,
- François Bachand,
- and Bin Tian
Genome Res. October 2017 27: 1685-1695; Published in Advance September 15, 2017, doi:10.1101/gr.222331.117
...from cell cycle and reach a quiescent state (Hoffman et al. 2015). We next asked whether APA profiles change in cells growing in rich versus minimal media. Using the top two most abundant 3′ UTR PAS isoforms of each gene, we examined the global 3′ UTR APA trend. We found that genes with up...

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