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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...on potentially misleading predictions.Prediction of potential regulatory sitesThis review focuses on gene-specific transcriptional regulation via direct TF binding to regulatory DNA sites. The initial task is thus to locate candidate DNA regions potentially involved in TF binding, and this starts...
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Research: Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts
- Yanis Zekri,
- Sebastian Gregoricchio,
- Elif Yapıcı,
- Chia-Chi Flora Huang,
- Tunç Morova,
- Umut Berkay Altıntaş,
- Gozde Korkmaz,
- Nathan A. Lack,
- and Wilbert Zwart
Genome Res. July 2025 35: 1530-1543; Published in Advance June 10, 2025, doi:10.1101/gr.280320.124
...samples reveal distinct transcription complex compositions, 3D contexts, and regulatory dynamics associated with different classes of ESR1 binding sites. Overall, our results establish a comprehensive framework to highlight and elucidate the molecular basis underlying ESR1 genomic heterogeneity and its...
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Method: Early feature extraction drives model performance in high-resolution chromatin accessibility prediction
- Aayush Grover,
- Till Muser,
- Liine Kasak,
- Lin Zhang,
- Ekaterina Krymova,
- and Valentina Boeva
Genome Res. March 2026 36: 619-629; Published in Advance January 12, 2026, doi:10.1101/gr.281042.125
...for genomic data. Integrated into diverse architectures such as convoluted neural networks (CNNs), long short-term memory (LSTM), dilated CNNs, and transformers, ConvNeXt V2 blocks consistently improve performance, leading to similar prediction accuracy across these different model types. This reveals...
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Resource: Quadrupia provides a comprehensive catalog of G-quadruplexes across genomes from the tree of life
- Nikol Chantzi,
- Akshatha Nayak,
- Fotis A. Baltoumas,
- Eleni Aplakidou,
- Shiau Wei Liew,
- Jesslyn Elvaretta Galuh,
- Michail Patsakis,
- Austin Montgomery,
- Camille Moeckel,
- Ioannis Mouratidis,
- Saiful Arefeen Sazed,
- Wilfried Guiblet,
- Panagiotis Karmiris-Obratański,
- Guliang Wang,
- Apostolos Zaravinos,
- Karen M. Vasquez,
- Chun Kit Kwok,
- Georgios A. Pavlopoulos,
- and Ilias Georgakopoulos-Soares
Genome Res. November 2025 35: 2578-2600; Published in Advance August 26, 2025, doi:10.1101/gr.279790.124
...://www.pavlopoulos-lab.org/quadrupia), the largest and, to our knowledge, most comprehensive database of putative G4 DNA-forming sequences to date, covering 108,534 species and encompassing 87,160,084 putative G4 DNA-forming sequences. The experimental validation of highly prevalent G4s across the tree of life suggests that our predictions...
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Research: Transcription and potential functions of a novel XIST isoform in male peripheral glia
- Kevin S. O'Leary,
- Meng-Yen Li,
- Kevyn Jackson,
- Lijie Shi,
- Elena Ezhkova,
- Bernice E. Morrow,
- and Deyou Zheng
Genome Res. February 2026 36: 257-274; Published in Advance December 12, 2025, doi:10.1101/gr.280832.125
..., SOX10, TCF4, ETS1, SREBF1, CEBPB, KLF2, and ETV5) were higher in either skeletal muscle or heart nonmyelinating Schwann cells. Analysis of the transcription regulatory programs by the SCENIC software predicted that FOXO1 (and YY1) could regulate XIST in heart and skeletal muscle Schwann cells...
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Method: Automated interpretable artificial intelligence genomic prediction with AIGP
- Lei Wei,
- Ziqin Jiang,
- Baoliang Fan,
- Yidan Yan,
- Zhenqiang Xu,
- Xiaoxiang Hu,
- and Yuzhe Wang
Genome Res. March 5, 2026 gr.281006.125; Published in Advance March 5, 2026, doi:10.1101/gr.281006.125
.... To date, the 72 relationship between ML's predictive accuracy and the aforementioned parameters, 73 particularly when applied to different traits, remains inadequately analyzed and lacks 74 comprehensiveness (Reel et al. 2021; Lourenço et al. 2024). 75 ML models often struggle to elucidate...
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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 gr.280838.125; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
...RNA-seq on 28 hpf samples. 151 This revealed strong enrichment for transcripts expressed in specific endoderm cell 152 populations including pancreatic, liver and intestinal markers (Fig. 1D, Supplemental Fig. 2, 153 Supplemental Table 1). However, we also note enrichment of markers of fin epithelia...
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Resource: Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease
- Kangli Wang,
- Weikun Xia,
- Yingli Gu,
- Songpeng Zu,
- Qian Yang,
- Maria Luisa Amaral,
- Yaozhi Wang,
- Allen Wang,
- Xiang-Dong Fu,
- William C. Mobley,
- and Bing Ren
Genome Res. March 4, 2026 gr.281113.125; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...networks(Lee and Young 2013; Levine 66 et al. 2014; Long et al. 2016). Understanding these regulatory mechanisms beyond transcription 67 may reveal critical aspects of how cellular changes during aging contribute to PD pathology. 68 A pivotal study employing the multiome technique in human aging and PD...
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Method: Kinetic measurement of gene-specific RNA polymerase II transcription elongation rates
- Haiyue Liu and
- Lea H. Gregersen
Genome Res. November 2025 35: 2550-2562; Published in Advance October 22, 2025, doi:10.1101/gr.280852.125
...rate) and successfully transcribes the full-length RNA (i.e., processivity) (Muniz et al. 2021).Advances in biochemical and high-throughput technologies have revealed that transcription elongation rates are highly regulated (Muniz et al. 2021). For example, depletion of elongation factor Paf1C...
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Research: Genome-wide nucleosome and transcription factor responses to genetic perturbations reveal chromatin-mediated mechanisms of transcriptional regulation
- Kevin Moyung,
- Yulong Li,
- Heather K. MacAlpine,
- Alexander J. Hartemink,
- and David M. MacAlpine
Genome Res. January 2026 36: 115-128; Published in Advance December 9, 2025, doi:10.1101/gr.279637.124
...with the up- and downregulation of genes and use these signatures to reveal regulatory mechanisms previously unexplored in expression-based studies. Finally, we demonstrate that chromatin features are predictive of transcriptional activity, and we leverage these features to reconstruct chromatin...

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