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Method: RNA-DNA hybrid (R-loop) immunoprecipitation mapping: an analytical workflow to evaluate inherent biases
- László Halász,
- Zsolt Karányi,
- Beáta Boros-Oláh,
- Tímea Kuik-Rózsa,
- Éva Sipos,
- Éva Nagy,
- Ágnes Mosolygó-L,
- Anett Mázló,
- Éva Rajnavölgyi,
- Gábor Halmos,
- and Lóránt Székvölgyi
Genome Res. June 2017 27: 1063-1073; Published in Advance March 24, 2017, doi:10.1101/gr.219394.116
...by a few laboratories, without paying attention to the potential caveats that might affect the outcome of RNA-DNA hybrid mapping. To assess the accuracy and utility of this technology, we pursued an analytical approach to estimate inherent biases and errors in the DRIP protocol. By performing DRIP...
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Method: Deep structural clustering reveals hidden systematic biases in RNA sequencing data
- Qiang Su,
- Yi Long,
- Deming Gou,
- Junmin Quan,
- Xiaoming Zhou,
- and Qizhou Lian
Genome Res. November 2025 35: 2563-2577; Published in Advance September 19, 2025, doi:10.1101/gr.280713.125
...and colored by its GMM cluster label. Each k-mer is associated with a theoretical modeling count and an empirical sequencing count; these counts are aggregated based on cluster labels. The correlation between these aggregates evaluates how high-dimensional structural features determine sequencing biases...
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Research: Pangenome analysis reveals families of ubiquitin-ligase adaptors as key genomic divergence drivers that lead to hybrid incompatibility
- Dongying Xie,
- Pohao Ye,
- Yiming Ma,
- and Zhongying Zhao
Genome Res. March 2026 36: 506-521; Published in Advance February 17, 2026, doi:10.1101/gr.280885.125
.... 2020; Jiao et al. 2025). These interactions often fuel hybrid genomic conflicts. Short-read sequencing technologies have struggled to resolve such complexities owing to inherent limitations in assembly. In contrast, the advent of long-read sequencing technologies, such as of Pacific Biosciences (Pac...
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Method: Analytical validation of germline small variant detection using long-read HiFi genome sequencing
- Nathan Hammond,
- Linda Liao,
- Pun Wai Tong,
- Zena Ng,
- Thuy-Mi P. Nguyen,
- Chandler Ho,
- Yao Yang,
- and Stuart A. Scott
Genome Res. June 2025 35: 1391-1399; Published in Advance April 11, 2025, doi:10.1101/gr.278836.123
...of diagnostic long-read HiFi sequencing, we executed an analytical validation plan that was centered on comprehensively evaluating HiFi sequencing for germline SNV/indel detection and specimen types that are used for clinical testing in medical genetics. Results were stratified by variant type and GIAB...
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Method: A high-throughput screening method for selecting feature SNPs to evaluate breed diversity and infer ancestry
- Meilin Zhang,
- Heng Du,
- Yu Zhang,
- Yue Zhuo,
- Zhen Liu,
- Yahui Xue,
- Lei Zhou,
- Sixuan Zhou,
- Wanying Li,
- and Jian-Feng Liu
Genome Res. August 2025 35: 1875-1886; Published in Advance July 15, 2025, doi:10.1101/gr.280176.124
...for efficient and accurate discovery of the breed diversities of species and ancestries of populations are needed.Breed diversity can be evaluated through genetic or phenotypic analyses, each offering unique insights (Reist-Marti et al. 2003). Traditionally, genetic diversity assessments relied on pedigree...
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Method: High-resolution spatial transcriptomics in fixed tissue using a cost-effective PCL-seq workflow
- Xue Dong,
- Mengzhu Hu,
- Xiaonan Cui,
- Wenjian Zhou,
- Jingtao Cai,
- Guangyao Mao,
- and Weiyang Shi
Genome Res. September 2025 35: 2052-2063; Published in Advance August 5, 2025, doi:10.1101/gr.279906.124
...compatibility. PCL-seq is based on poly(A) priming and thus works with a wide range of species, from animal to plant, theoretically. In comparison, commercial platforms like GeoMx DSP rely on species-specific hybridization probes, limiting their use primarily to human and murine studies. (3) Simplified workflow...
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Resource: Human proteins that interact with RNA/DNA hybrids
- Isabel X. Wang,
- Christopher Grunseich,
- Jennifer Fox,
- Joshua Burdick,
- Zhengwei Zhu,
- Niema Ravazian,
- Markus Hafner,
- and Vivian G. Cheung
Genome Res. September 2018 28: 1405-1414; Published in Advance August 14, 2018, doi:10.1101/gr.237362.118
...and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892, USA Corresponding author: vgcheung@med.umich.eduAbstractRNA/DNA hybrids form when RNA hybridizes with its template DNA generating a three-stranded structure known as the R-loop. Knowledge of how they form and resolve, as well as their functional roles...
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Resource: Haplotype-resolved 3D chromatin architecture of the hybrid pig
- Yu Lin,
- Jing Li,
- Yiren Gu,
- Long Jin,
- Jingyi Bai,
- Jiaman Zhang,
- Yujie Wang,
- Pengliang Liu,
- Keren Long,
- Mengnan He,
- Diyan Li,
- Can Liu,
- Ziyin Han,
- Yu Zhang,
- Xiaokai Li,
- Bo Zeng,
- Lu Lu,
- Fanli Kong,
- Ying Sun,
- Yongliang Fan,
- Xun Wang,
- Tao Wang,
- An'an Jiang,
- Jideng Ma,
- Linyuan Shen,
- Li Zhu,
- Yanzhi Jiang,
- Guoqing Tang,
- Xiaolan Fan,
- Qingyou Liu,
- Hua Li,
- Jinyong Wang,
- Li Chen,
- Liangpeng Ge,
- Xuewei Li,
- Qianzi Tang,
- and Mingzhou Li
Genome Res. February 2024 34: 310-325; Published in Advance March 13, 2024, doi:10.1101/gr.278101.123
..., skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data...
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Research: RNA–DNA sequence differences in Saccharomyces cerevisiae
- Isabel X. Wang,
- Christopher Grunseich,
- Youree G. Chung,
- Hojoong Kwak,
- Girish Ramrattan,
- Zhengwei Zhu,
- and Vivian G. Cheung
Genome Res. November 2016 26: 1544-1554; Published in Advance September 16, 2016, doi:10.1101/gr.207878.116
...that RDD formation is affected by mutations in genes regulating R-loops. Loss-of-function mutations in ribonuclease H, senataxin, and topoisomerase I that resolve RNA–DNA hybrids lead to increases in RDD frequency. Our results demonstrate that RDD is a conserved process that diversifies transcriptomes...
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Method: Characterization of meiotic recombination intermediates through gene knockouts in founder hybrid mice
- Benjamin Davies,
- Gang Zhang,
- Daniela Moralli,
- Samy Alghadban,
- Daniel Biggs,
- Chris Preece,
- Peter Donnelly,
- and Anjali Gupta Hinch
Genome Res. November 2023 33: 2018-2027; Published in Advance November 17, 2023, doi:10.1101/gr.278024.123
...level, we generated maps of in vivo binding of RPA and RAD51 in candidate knockout founder mice. Specifically, we performed chromatin immunoprecipitation (ChIP) followed by ssDNA sequencing (ChIP-seq) (Khil et al. 2012) for RAD51 and RPA (Hinch et al. 2020) in testes of the adult male Dmc1−/− hybrid...
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