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Method: EnDeep4mC predicts DNA N⁴-methylcytosine sites using a dual-adaptive feature encoding framework in deep ensembles
- Shuyu Zhang,
- Quan Zou,
- Mengting Niu,
- Zhibin Lv,
- Antony Stalin,
- and Ximei Luo
Genome Res. March 2026 36: 589-599; Published in Advance February 17, 2026, doi:10.1101/gr.280977.125
...capturing local conserved patterns, long-range context dependence, and global attention correlations of DNA sequences.To address these limitations, we propose EnDeep4mC, a dual-adaptive optimization framework. The core innovations of EnDeep4mC include (1) a species-model collaborative mechanism...
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Method: Iterative improvement of deep learning models using synthetic regulatory genomics
- André M. Ribeiro-dos-Santos and
- Matthew T. Maurano
Genome Res. November 2025 35: 2539-2549; Published in Advance October 22, 2025, doi:10.1101/gr.280540.125
...York University Grossman School of Medicine, New York, New York 10016, USA Corresponding author: maurano@nyu.eduAbstractDeep learning models can accurately reconstruct -wide epigenetic tracks from the reference sequence alone. But it is unclear what predictive power they have on sequence diverging from...
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Research: Strong bias in long-read sequencing prevents assembly of Drosophila melanogaster Y-linked genes
- A. Bernardo Carvalho,
- Bernard Y. Kim,
- and Fabiana Uno
Genome Res. January 2026 36: 71-82; Published in Advance October 1, 2025, doi:10.1101/gr.280604.125
...reads produced by deep sequencing with state-of-the-art Nanopore (10.4 flow cells, 200× coverage) and PacBio (HiFi 50×). The same exons are accurately assembled using Illumina 67× coverage. We find that these missing exons are consistently located near simple satellite sequences, in which sequencing...
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Research: A massively parallel reporter assay reveals context-dependent activity of homeodomain binding sites in vivo
- Andrew E.O. Hughes,
- Connie A. Myers,
- and Joseph C. Corbo
Genome Res. October 2018 28: 1520-1531; Published in Advance August 29, 2018, doi:10.1101/gr.231886.117
...but at lower levels. Of note, all of these factors are down-regulated by P14 and are not expressed in adult photoreceptors (Sowden et al. 2001), suggesting that TBX TFs may regulate photoreceptor gene expression specifically at early post-natal stages.In addition to identifying sequence features...
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Research: Analysis of canine gene constraint identifies new variants for orofacial clefts and stature
- Reuben M. Buckley,
- Nüket Bilgen,
- Alexander C. Harris,
- Peter Savolainen,
- Cafer Tepeli,
- Metin Erdoğan,
- Aitor Serres Armero,
- Dayna L. Dreger,
- Frank G. van Steenbeek,
- Marjo K. Hytönen,
- Heidi G. Parker,
- Jessica Hale,
- Hannes Lohi,
- Bengi Çınar Kul,
- Adam R. Boyko,
- and Elaine A. Ostrander
Genome Res. May 2025 35: 1080-1093; Published in Advance March 24, 2025, doi:10.1101/gr.280092.124
...by noncoding variation surrounding and likely regulating highly constrained genes. Further investigation is required to identify trait-associated noncoding variants and candidate gene regulatory regions.DiscussionArtificial selection for desired traits has made the domestic dog one of the most phenotypically...
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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 2D models in capturing the full complexity of higher-order structural influences, we propose a novel three-dimensional (3D) approach. This 3D analysis leverages a deep-learning variational autoencoder-Gaussian mixture model (VAE-GMM) to examine the high-dimensional structural similarities of k...
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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
...trained a deep neural network, which pinpointed the causal variant for strong effect variants with >90% accuracy. Taken together, this study provides a functional assessment of the sequence requirements for the occupancy of four essential regulators and identifies new dependency relationships...
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Research: Optical genome mapping identifies rare structural variants in neural tube defects
- Nikhil S. Sahajpal,
- Jane Dean,
- Benjamin Hilton,
- Timothy Fee,
- Cindy Skinner,
- Alex Hastie,
- Barbara R. DuPont,
- Alka Chaubey,
- Michael J. Friez,
- and Roger E. Stevenson
Genome Res. April 2025 35: 798-809; Published in Advance March 19, 2025, doi:10.1101/gr.279318.124
...SVs impacting genes implicated in the neural tube development pathways. This study identifies RMND5A, HNRNPC, FOXD4, and RBBP4 as strong candidate genes associated with NTDs, and expands the phenotypic spectrum of AMER1 and TGIF1 to include NTDs. This study constitutes the first systematic...
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Method: Modeling gene interactions in polygenic prediction via geometric deep learning
- Han Li,
- Jianyang Zeng,
- Michael P. Snyder,
- and Sai Zhang
Genome Res. January 2025 35: 178-187; Published in Advance November 19, 2024, doi:10.1101/gr.279694.124
...-Net, an interpretable geometric deep learning–based framework that effectively models the nonlinearity of biological systems for enhanced disease prediction and biological discovery. PRS-Net begins by deconvoluting the -wide PRS at the single-gene resolution and then explicitly encapsulates gene–gene interactions...
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Research: Large-scale mapping of gene regulatory logic reveals context-dependent repression by transcriptional activators
- David van Dijk,
- Eilon Sharon,
- Maya Lotan-Pompan,
- Adina Weinberger,
- Eran Segal,
- and Lucas B. Carey
Genome Res. January 2017 27: 87-94; Published in Advance December 13, 2016, doi:10.1101/gr.212316.116
..., green, blue) or adding a polyT nucleosome disfavoring sequence (green, red). IDs show library construct identifiers.The measurements were carried out using our previously described method that involves FACS sorting and deep sequencing of a barcoded pooled promoter library (Sharon et al. 2012, 2014...

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