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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
...DNA accessibility and RNA transcription across these engineered sequences when delivered at their endogenous loci. At a high level, we observe a good correlation between accessibility predicted by Enformer and experimental data. But model performance is best for sequences that more resembled...
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Method: Scalable cell-specific coexpression networks for granular regulatory pattern discovery with NeighbourNet
- Yidi Deng,
- Jiadong Mao,
- Jarny Choi,
- and Kim-Anh Lê Cao
Genome Res. April 2026 36: 785-801; Published in Advance March 5, 2026, doi:10.1101/gr.281171.125
...expression in biological systems. At the core of these networks lies the inference of gene regulation, which reflects the binding of transcription factors (TFs) to specific DNA sequences to either activate or repress target gene expression. This regulation directs crucial cellular processes...
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Method: spRefine denoises and imputes spatial transcriptomic data with a reference-free framework powered by genomic language model
- Tianyu Liu,
- Tinglin Huang,
- Wengong Jin,
- Tinyi Chu,
- Rex Ying,
- and Hongyu Zhao
Genome Res. April 2026 36: 754-768; Published in Advance February 3, 2026, doi:10.1101/gr.281001.125
...among genes. However, this method is limited to the imputation of protein-coding genes. To simultaneously impute and denoise gene expression profiles, we may consider genomic language models (gLMs) (Avsec et al. 2021; de Almeida and Pierrot 2022; Benegas et al. 2025), which model DNA sequence...
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Resource: Cell type–specific gene regulatory atlas prioritizes drug targets and repurposable medicines in Alzheimer's disease
- Yunxiao Ren,
- Ming Hu,
- Yang E. Li,
- Andrew A. Pieper,
- Jeffrey Cummings,
- and Feixiong Cheng
Genome Res. March 2026 36: 645-659; Published in Advance January 21, 2026, doi:10.1101/gr.280436.125
...–specific cis-regulatory DNA elements (CREs), we pinpoint 141 ADNC-associated genes. Using gene set enrichment analysis (GSEA) and network proximity analysis, we further identify nine candidate repurposable drugs that were associated with these ADNC-related genes. In summary, this cell type–specific multiomic...
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Research: Functional genomics analysis of developing zebrafish and human endoderm reveals highly conserved cis-regulatory modules acting during vertebrate organogenesis
- Daniela M. Riley,
- Randa Elsayed,
- Mark D. Walsh,
- Simaran Johal,
- Ying Lin,
- Harry Walton,
- Till Bretschneider,
- Sascha Ott,
- and Andrew C. Nelson
Genome Res. April 2026 36: 695-712; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
...and compared with all HCNEs (Fig. 4H; Supplemental Figs. S14–S18).Consistent with expectations, our analyses reveal a highly significant association between endoderm HCNEs and genes encoding DNA-binding and gene regulatory proteins, including HMG domain-containing and chromatin binding factors. Notably...
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Resource: A systems view on DNA damage response kinetics in Tetrahymena
- Emily Nischwitz,
- Vivien A.C. Schoonenberg,
- Rachel Mullner,
- Albert Fradera-Sola,
- Susanne Zimbelmann,
- Joshua J. Smith,
- and Falk Butter
Genome Res. January 28, 2026 ; Published in Advance January 28, 2026, doi:10.1101/gr.281000.125
...Chaudhuri A, Nussenzweig A. 2017. Themultifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol 18: 610– 621. doi:10.1038/nrm.2017.53 R Core Team. 2022. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. https...
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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
..., providing actionable insights into ensemble architecture design in DL frameworks.Comparison with existing predictorsTo verify the performance of EnDeep4mC, we systematically compared it against five DL models (4mCCNN, Deep4mC, Hyb4mC, DeepSF-4mC, and EpiTEAmDNA) and one traditional ML model (4mc...
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Method: A scalable computational framework for predicting gene expression from candidate cis-regulatory elements
- Qinhu Zhang,
- Siguo Wang,
- Zhipeng Li,
- Wenzheng Bao,
- Wenjian Liu,
- and De-Shuang Huang
Genome Res. February 2026 36: 361-374; Published in Advance January 16, 2026, doi:10.1101/gr.281219.125
...for predicting gene expression (ScPGE) from discrete candidate CREs (cCREs). ScPGE assembles DNA sequences, transcription factor (TF) binding scores, and epigenomic tracks from discrete cCREs into three-dimensional tensors, and then models the relationships between cCREs and genes by combining convolutional...
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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
.... 2019; Singh et al. 2019; Buikema et al. 2020). GSK3i promotes cell cycling, marked by DNA synthesis and mitosis; reduced cell ploidy; and sarcomere disassembly—all markers of CM immaturity (Mollova et al. 2013; Mills et al. 2019; Singh et al. 2019; Buikema et al. 2020).CHIR99021 (CHIR) is a potent GSK3...
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Research: Genomic regulatory landscape underlying the antiviral response of Atlantic salmon
- Shahmir Naseer,
- Thomas C Clark,
- Bertrand Collet,
- Pooran Dewari,
- Damir Baranasic,
- Daniel J Macqueen,
- Pierre Boudinot,
- and Samuel A.M. Martin
Genome Res. October 22, 2025 gr.280579.125; Published in Advance October 22, 2025, doi:10.1101/gr.280579.125
...such as histone acetylation and methylation contribute to 48 this regulation by altering DNA accessibility at enhancers and promoters (Mostafavi et al., 49 2016; Kan et al., 2022). Transposase-accessible chromatin with sequencing (ATAC-seq) 50 and chromatin immunoprecipitation and sequencing (ChIP-seq) are widely...
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