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Method: PoreMeth2 for decoding the evolution of methylome alterations with nanopore sequencing
- Gianluca Mattei,
- Marta Baragli,
- Barbara Gega,
- Alessandra Mingrino,
- Martina Chieca,
- Tommaso Ducci,
- Gianmaria Frigè,
- Luca Mazzarella,
- Romina D'Aurizio,
- Francesco De Logu,
- Romina Nassini,
- Pier Giuseppe Pelicci,
- and Alberto Magi
Genome Res. November 2025 35: 2501-2512; Published in Advance October 20, 2025, doi:10.1101/gr.280259.124
...differential methylation studies to just 50% of the human methylome. Nanopore sequencing, with its long reads, enables the analysis of epiallele frequency across both high and low CpG density regions. Here, we introduce a novel computational approach, PoreMeth2, an R library that integrates epiallelic...
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Research: Characterization of the distribution and dynamics of chromatin states in the C. elegans germline reveals substantial H3K4me3 remodeling during oogenesis
- Mariateresa Mazzetto,
- Lauren E. Gonzalez,
- Nancy Sanchez,
- and Valerie Reinke
Genome Res. January 2024 34: 57-69; Published in Advance December 26, 2023, doi:10.1101/gr.278247.123
...transcription, the accompanying changes to chromatin structure and how those changes contribute to correct activation in the early embryo are not well characterized (Robert et al. 2015).Functional and genomic studies have revealed some epigenetic regulatory mechanisms that influence germline chromatin...
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Research: Expanded methylome and quantitative trait loci detection by long-read profiling of personal DNA
- Cristian Groza,
- Bing Ge,
- Warren A. Cheung,
- Tomi Pastinen,
- and Guillaume Bourque
Genome Res. April 2025 35: 644-652; Published in Advance March 20, 2025, doi:10.1101/gr.279240.124
...from the CHM13v2 reference (SV-CpGs), thus expanding their number by 43.6%. Using 435 methylomes, we genotyped 4.06 million SV-CpGs, of which 3.93 million (96.8%) are methylated at least once. Nonrepeat sequences contribute 1.59 × 106 novel SV-CpGs, followed by centromeric satellites (6.57 × 105...
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Research: KRAB zinc-finger proteins regulate endogenous retroviruses to sculpt germline transcriptomes and genome evolution
- Kai Otsuka,
- Akihiko Sakashita,
- So Maezawa,
- Richard M. Schultz,
- and Satoshi H. Namekawa
Genome Res. March 2025 35: 417-431; Published in Advance March 12, 2025, doi:10.1101/gr.279924.124
...in meiosis, suggesting that meiotic sex chromosome inactivation (MSCI) may antagonize the coevolution of KZFPs and ERVs in mammals. Our study uncovers a mechanism by which a subset of KZFPs regulate ERVs to sculpt germline transcriptomes. We propose that epigenetic programming during the transition from...
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Research: Incomplete erasure of histone marks during epigenetic reprogramming in medaka early development
- Hiroto S. Fukushima,
- Hiroyuki Takeda,
- and Ryohei Nakamura
Genome Res. April 2023 33: 572-586; Published in Advance April 28, 2023, doi:10.1101/gr.277577.122
...analyzed histone modification dynamics during epigenetic reprogramming in Japanese killifish, medaka (Oryzias latipes) embryos. Our data revealed that H3K27ac, H3K27me3, and H3K9me3 escape complete reprogramming, whereas H3K4 methylation is completely erased during cleavage stage. Furthermore, we...
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Method: Genotyping of selected germline adaptive immune system loci using short-read sequencing data
- Michael K.B. Ford,
- Ananth Hari,
- Meredith Yeager,
- Lisa Mirabello,
- Stephen Chanock,
- Ibrahim Numanagić,
- COVNET Consortium,
- and S. Cenk Sahinalp
Genome Res. September 2025 35: 2076-2086; Published in Advance August 5, 2025, doi:10.1101/gr.280314.124
...a cohort of 461 COVID-19 patients from the COVNET Consortium.ResultsMendelian concordance analysis reveals strong concordance across immune lociWe applied ImmunoTyper2 to genotype 590 parent–child trios from the 1kGP. Processing times varied by locus, ranging from 12 min for TRAV and TRBV to 63 min...
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Method: Simultaneous assessment of human genome and methylome data in a single experiment using limited deamination of methylated cytosine
- Bo Yan,
- Duan Wang,
- and Laurence Ettwiller
Genome Res. June 2024 34: 904-913; Published in Advance June 10, 2024, doi:10.1101/gr.278294.123
...- or targeted- sequencing show the same germline variation calling accuracy and sensitivity compared with standard DNA-seq. Additionally, regional methylation levels provide an accurate map of the human methylome.Cytosine methylation is the main epigenetic DNA modification found in higher Eukaryotes. In humans...
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Method: TFcomb identifies transcription factor combinations for cellular reprogramming based on single-cell multiomics data
- Chen Li,
- Sijie Chen,
- Yixin Chen,
- Haiyang Bian,
- Minsheng Hao,
- Lei Wei,
- and Xuegong Zhang
Genome Res. June 2025 35: 1429-1439; Published in Advance April 10, 2025, doi:10.1101/gr.279955.124
...of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China Corresponding author: weilei92@tsinghua.edu.cnAbstractReprogramming cell state transitions provides the potential for cell engineering and regenerative therapy. Finding the reprogramming transcription factors (TFs...
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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: Combinatorial microRNA activity is essential for the transition of pluripotent cells from proliferation into dormancy
- Dhanur P. Iyer,
- Lambert Moyon,
- Lars Wittler,
- Chieh-Yu Cheng,
- Francisca R. Ringeling,
- Stefan Canzar,
- Annalisa Marsico,
- and Aydan Bulut-Karslioğlu
Genome Res. April 2024 34: 572-589; Published in Advance May 6, 2024, doi:10.1101/gr.278662.123
...and others have revealed significant rewiring of the metabolic, epigenetic, and transcriptomic signatures of cells in this transition (Fu et al. 2014; Boroviak et al. 2015; Hussein et al. 2020; Collignon et al. 2023; Iyer et al. 2023; van der Weijden et al. 2024). Among these are altered RNA methylation...

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