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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
...@eitech.edu.cnAbstractDeciphering the relationships between cis-regulatory elements (CREs) and target gene expression has been a long-standing unsolved problem in molecular biology, and the dynamics of CREs in different cell types make this problem more challenging. To address this challenge, we propose a scalable computational framework...
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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. March 5, 2026 ; Published in Advance March 5, 2026, doi:10.1101/gr.281171.125
...stronger regulatory relevance than expression alone, and therefore produce TF activity scores that more accurately capture true cellular states. To validate this, we benchmarked activity scores derived from expression (ETAS, expression-based TF activity scores) against those derived from coexpression (Co...
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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
...catalog, excluding 23andMe samples. These loci were intersected with cell type–specific cCREs (FDR ≤ 0.05, |log2FC| > 0.5) to link genetic variants with putative regulatory elements.Identification of positive TF-regulators and putative targetsTo infer TF-regulators, we correlated motif accessibility...
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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
...for downstream TFBS analysis, allowing the 142 identification of key regulatory motifs involved in the antiviral response. 143 To further characterise the genomic distribution of ATAC-seq and H3K27ac peaks, we 144 annotated consensus peaks relative to gene features and transcription start sites (TSS). The 145...
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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
...with shorter input windows (Karollus et al. 2023), we adapted the published Enformer model to use flexible input and output lengths to enable capturing relevant regulatory elements while maintaining high computational efficiency, as well as outputting predictions for large synthetic payloads (Methods). We...
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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. March 4, 2026 ; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
...disparate vertebrate species is therefore generally lacking. Identification of tissue-specific CRMs and their key operative TFs is pivotal to understanding how gene regulatory control of cell fate decisions is achieved during normal development. Furthermore, to understand the basis for developmental...
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Method: Recovering gene regulatory networks in single-cell multi-omics data with PRISM-GRN
- Wenhao Zhang,
- Lan Cao,
- Xiaoxuan Gu,
- Yongyu Long,
- and Ying Wang
Genome Res. January 2026 36: 142-158; Published in Advance October 9, 2025, doi:10.1101/gr.280757.125
...to comprehensively map GRNs (Badia-i-Mompel et al. 2023). High-throughput RNA sequencing (RNA-seq), which enables -wide analysis of the cellular transcriptome on bulk cells (Ozsolak and Milos 2011), has revolutionized GRN inference by enabling the computational derivation of regulatory networks from gene expression...
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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
...; Love et al. 2014). ATAC-seq profiles surrounding the MYH6 locus (Fig. 1F,G) were visualized in the Integrative Genomics Viewer (IGV) (Robinson et al. 2011). The identification of TF binding motifs in differentially accessible regions was performed using the MEME suite (v5.5.7) (Supplemental Table S2...
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Resource: Multitissue single-nucleus RNA-seq reveals cell type–specific regulatory patterns of alternative polyadenylation in pigs
- Qiuhan Wen,
- Zhen Wang,
- Qi Bao,
- Tianli Ding,
- Haihan Zhang,
- Jianbo Li,
- Zhuang Liu,
- Jieping Huang,
- and Guoqiang Yi
Genome Res. September 2025 35: 2116-2129; Published in Advance June 16, 2025, doi:10.1101/gr.280095.124
...of ELAVL1 and ELAVL2, which play a crucial role in spermatogonia by promoting cell proliferation and preventing apoptosis. Although our computational evidence supports this model, experimental validation using techniques such as RNA-EMSA, CLIP-seq, and cell type–specific perturbation is necessary. However...
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Research: Wnt signaling activation induces CTCF binding and loop formation at cis-regulatory elements of target genes
- Anna Nordin,
- Chaitali Chakraborty,
- Mattias Jonasson,
- Orgena Dano,
- Gianluca Zambanini,
- Pierfrancesco Pagella,
- Silvia Remeseiro,
- and Claudio Cantù
Genome Res. August 2025 35: 1701-1716; Published in Advance June 23, 2025, doi:10.1101/gr.279684.124
...as beta-catenin) drives the expression of target genes from regulatory regions bound by TCF/LEF transcription factors. Gene regulation, however, entails the interplay between sequence information and 3D structure, yet the impact of Wnt signaling on structure has been poorly explored. Here, we investigate...
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