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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
..., hinging on the precise binding of transcription factors (TFs) and cofactors to gene regulatory elements such as promoters and enhancers. Although it is relatively routine to profile -wide DNA binding landscapes of proteins, identifying the specific proteins that bind to, and regulate the transcription of...
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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
..., and interpretable exploration of causal GRNs with prior knowledge and multi-omics data.Gene regulatory networks (GRNs), which encapsulate the complex interactions among transcription factors (TFs), target genes, and various regulatory elements, constitute the core machinery of gene regulation (Levine and Davidson...
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Method: Aggregation of recount3 RNA-seq data improves inference of consensus and tissue-specific gene coexpression networks
- Prashanthi Ravichandran,
- Princy Parsana,
- Rebecca Keener,
- Kasper D. Hansen,
- and Alexis Battle
Genome Res. September 2025 35: 2087-2103; Published in Advance July 17, 2025, doi:10.1101/gr.280808.125
...-specific networks. Central genes in consensus networks are enriched for evolutionarily constrained genes and ubiquitous biological pathways, whereas context-specific central nodes include tissue-specific transcription factors. The increased statistical power from data aggregation facilitates the derivation...
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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
...(regulatory) relationships by associating gene expression at successive points in the trajectory. Despite their advantages, CSN inference faces key challenges in both scalability and stability. Inferring networks for thousands of cells is computationally intensive and often restricted to transcription factor...
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Method: Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution
- Paul Ashford,
- Alexander M. Frankell,
- Zofia Piszka,
- Camilla S.M. Pang,
- Mahnaz Abbasian,
- Maise Al Bakir,
- Mariam Jamal-Hanjani,
- Nicholas McGranahan,
- Charles Swanton,
- and Christine A. Orengo
Genome Res. March 2026 36: 561-577; Published in Advance February 19, 2026, doi:10.1101/gr.278663.123
...s (Van de Peer et al. 2009; Kondrashov 2012; Wang et al. 2012). Although increased ploidy following WGD incurs fitness costs to an organism, it can confer advantages during times of environmental change and stress, including increased adaptability and robustness of gene regulatory networks (Ebadi et...
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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
...are the mean log2FC for that group. (C) Heatmap of the DEGs (adjusted P-values < 0.05 and |fold change| > 1.5). (D,E) ToppFun results from downregulated (D) and upregulated (E) genes in C. (F) Boxplots showing the expression of XIST, DNAAF1, and HMMR. (G) Cloned XIST, DNAAF1, and HMMR transcript sequence...
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Method: Analysis of coding gene expression from small RNA sequencing
- Aygun Azadova,
- Anthonia Ekperuoh,
- Greg N. Brooke,
- and Antonio Marco
Genome Res. March 2026 36: 611-618; Published in Advance February 10, 2026, doi:10.1101/gr.281364.125
...-seq data are often unavailable. The lack of paired sequencing experiments limits the analysis of microRNA–gene regulatory networks. Here, we explore whether protein-coding gene expression can be quantified directly from transcript fragments present in sRNA-seq experiments. We analyze studies containing...
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Method: Diffusion-based generation of gene regulatory networks from scRNA-seq data with DigNet
- Chuanyuan Wang and
- Zhi-Ping Liu
Genome Res. February 2025 35: 340-354; Published in Advance December 18, 2024, doi:10.1101/gr.279551.124
....The transcriptional state of a cell is intricately controlled by a gene regulatory network (GRN) comprising numerous transcription factors (TFs) and their target genes. Coordinating with other regulatory elements, GRNs modulate the cell's phenotype, identity, and function in a dynamic and specific manner (Levine...
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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
...interplay of nucleosomes and TFs together in the context of transcriptional regulation is crucial for better understanding gene regulation within an organism.Although numerous efforts to construct gene regulatory networks (GRNs) have used -wide expression profiling under various genetic and environmental...
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Method: Parallel analysis of replication timing, gene expression, and copy number with PARTAGE
- Lakshana Sruthi Sadu Murari,
- Quinn Dickinson,
- Silvia Meyer-Nava,
- and Juan Carlos Rivera-Mulia
Genome Res. March 19, 2026 ; Published in Advance March 19, 2026, doi:10.1101/gr.281532.125
...to abnormal gene expression, instability, and structural variation in multiple diseases, including cancer. However, mechanistic links between RT, large-scale 3D architecture, and transcriptional regulation remain poorly understood. A major limitation is that current approaches require the separate profiling...
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