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Method: 3′-end ligation sequencing is a sensitive method to detect DNA nicks at potential sites of off-target activity induced by prime editors
- Jacob Stewart-Ornstein,
- Matthew J. Irby,
- Marina K. Lilieholm,
- Dylan Laprise,
- Maria D. Collier,
- Thomas Aunins,
- Dewi Harjanto,
- Aaron N. Chang,
- Deepak Reyon,
- and Jeremy S. Duffield
Genome Res. September 2025 35: 2064-2075; Published in Advance August 5, 2025, doi:10.1101/gr.280164.124
...off-target sites. Here we show that PEG-seq is an important addition to the off-target detection toolkit, enabling off-target discovery for DNA nicking gene editors such as prime editors.Biochemical methods for identifying sites in genomic DNA that are recognized or acted on by a protein or protein...
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Research: Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells
- Marcel Tarbier,
- Sebastian D. Mackowiak,
- Vaishnovi Sekar,
- Franziska Bonath,
- Etka Yapar,
- Bastian Fromm,
- Omid R. Faridani,
- Inna Biryukova,
- and Marc R. Friedländer
Genome Res. February 2026 36: 291-302; Published in Advance January 12, 2026, doi:10.1101/gr.279914.124
...RNAs induce expression variation at the RNA level, but some may buffer variation at the protein level. miRNAs that are themselves highly and variably expressed induce covariations between their targets. Lastly, miRNA primary transcripts can be robustly detected in whole-cell single-cell RNA-seq data, opening...
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Method: Dynamics of intronic polyadenylation in the hematopoietic lineage and its regulation by DNA methylation
- Richa Rashmi,
- Abhinaya Muruganandham,
- Pranita Borkar,
- Sumana Mallick,
- Taylor Hubbs,
- Ari Aviles,
- Daniel Chung,
- and Irtisha Singh
Genome Res. April 13, 2026 gr.281044.125; Published in Advance April 13, 2026, doi:10.1101/gr.281044.125
...1 Dynamics of intronic polyadenylation in the hematopoietic lineage and its 1 regulation by DNA methylation 2 Richa Rashmi1, Abhinaya Muruganandham1,2, Pranita Borkar1, Sumana Mallick1,2, Taylor 3 Hubbs1, Ari Aviles1,3, Daniel Chung1, Irtisha Singh1,2,3* 4 1Department of Cell Biology & Genetics...
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Research: Cell-type- and chromosome-specific chromatin landscapes and DNA replication programs of Drosophila testis tumor stem cell–like cells
- Jennifer A. Urban,
- Daniel Ringwalt,
- John M. Urban,
- Wingel Xue,
- Ryan Gleason,
- Keji Zhao,
- and Xin Chen
Genome Res. January 2026 36: 83-101; Published in Advance December 10, 2025, doi:10.1101/gr.280809.125
...-translational modifications, play a crucial role in regulating programs integral to a cell's identity, like gene expression and DNA replication. However, the transcriptional, chromatin, and replication timing profiles of adult stem cells in vivo remain poorly understood. Containing germline stem cells (GSCs) and somatic cyst...
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Research: Integrating genetic variation with deep learning provides context for variants impacting transcription factor binding during embryogenesis
- Olga M. Sigalova,
- Mattia Forneris,
- Frosina Stojanovska,
- Bingqing Zhao,
- Rebecca R. Viales,
- Adam Rabinowitz,
- Fayrouz Hammal,
- Benoît Ballester,
- Judith B. Zaugg,
- and Eileen E.M. Furlong
Genome Res. May 2025 35: 1138-1153; Published in Advance April 15, 2025, doi:10.1101/gr.279652.124
...during Drosophila embryogenesis. Using a combined haplotype test, we identified 9%–18% of TF-bound regions impacted by genetic variation even for essential regulators. By expanding WASP (a tool for allele-specific read mapping) to examine indels, we increased detection of allelically imbalanced peaks...
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Method: Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC
- Byron J. Smith,
- Chunyu Zhao,
- Veronika Dubinkina,
- Xiaofan Jin,
- Liron Zahavi,
- Saar Shoer,
- Jacqueline Moltzau-Anderson,
- Eran Segal,
- and Katherine S. Pollard
Genome Res. May 2025 35: 1247-1260; Published in Advance April 10, 2025, doi:10.1101/gr.279543.124
...in a microbial community, but they often fall short in characterizing variation in gene content between strains (Plaza Oñate et al. 2019). As a result, it is challenging to study the functional consequences of strain-level variation in the gut microbiome.The most common way to study microbial gene content...
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Research: Common cis-regulatory variation modifies the penetrance of pathogenic SHROOM3 variants in craniofacial microsomia
- Hao Zhu,
- Jiao Zhang,
- Soumya Rao,
- Matthew D. Durbin,
- Ying Li,
- Ruirui Lang,
- Jiqiang Liu,
- Baichuan Xiao,
- Hailin Shan,
- Ziqiu Meng,
- Jinmo Wang,
- Xiaokai Tang,
- Zhenni Shi,
- Liza L. Cox,
- Shouqin Zhao,
- Stephanie M. Ware,
- Tiong Y. Tan,
- Michelle de Silva,
- Lyndon Gallacher,
- Ting Liu,
- Jie Mi,
- Changqing Zeng,
- Hou-Feng Zheng,
- Qingguo Zhang,
- Stylianos E. Antonarakis,
- Timothy C. Cox,
- and Yong-Biao Zhang
Genome Res. May 2025 35: 1065-1079; Published in Advance April 15, 2025, doi:10.1101/gr.280047.124
...encompassed by GWAS signals in both cohorts (Supplemental Fig. 1). SHROOM3 was found to harbor the highest number of predicted deleterious coding variants in our cohorts and therefore became the focus of this study.Within the CFM cohort, 15,481 variants were detected across the SHROOM3 locus (including 100 kb...
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Method: k-mer manifold approximation and projection for visualizing DNA sequences
- Chengbo Fu,
- Einari A. Niskanen,
- Gong-Hong Wei,
- Zhirong Yang,
- Marta Sanvicente-García,
- Marc Güell,
- and Lu Cheng
Genome Res. May 2025 35: 1234-1246; Published in Advance April 10, 2025, doi:10.1101/gr.279458.124
..., Universitat Pompeu Fabra, 08003 Barcelona, Spain; 8Institució Catalana de Recerca i Estudis Avançats, ICREA, 08003 Barcelona, Spain Corresponding author: lu.cheng.ac@gmail.comAbstractIdentifying and illustrating patterns in DNA sequences are crucial tasks in various biological data analyses. In this task...
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Research: Variation in the fitness impact of translationally optimal codons among animals
- Florian Bénitière,
- Tristan Lefébure,
- and Laurent Duret
Genome Res. March 2025 35: 446-458; Published in Advance February 10, 2025, doi:10.1101/gr.279837.124
...indicates that in most species, intra-genomic variation in NSPs somehow contributes to the variance in SCU among genes. Hence, it is important to take this source of variance into account to be able to detect signatures of TS within s.tRNA abundance matches proteome requirementsTo quantify the intensity...
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Research: Analysis of a cell-free DNA–based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations
- Yasine Malki,
- Guannan Kang,
- W.K. Jacky Lam,
- Qing Zhou,
- Suk Hang Cheng,
- Peter P.H. Cheung,
- Jinyue Bai,
- Ming Lok Chan,
- Chui Ting Lee,
- Wenlei Peng,
- Yiqiong Zhang,
- Wanxia Gai,
- Winsome W.S. Wong,
- Mary-Jane L. Ma,
- Wenshuo Li,
- Xinzhou Xu,
- Zhuoran Gao,
- Irene O.L. Tse,
- Huimin Shang,
- L.Y. Lois Choy,
- Peiyong Jiang,
- K.C. Allen Chan,
- and Y.M. Dennis Lo
Genome Res. January 2025 35: 31-42; Published in Advance November 27, 2024, doi:10.1101/gr.279667.124
...its release and clearance. We hypothesized that cfDNA clearance by nucleases might be one mechanism that contributes toward inter-individual variations in cfDNA concentrations. We performed fragmentomic analysis of the plasma cfDNA from 862 healthy individuals, with a cfDNA concentration range of 1...
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