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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 Le Cao
Genome Res. March 5, 2026 gr.281171.125; Published in Advance March 5, 2026, doi:10.1101/gr.281171.125
...Gene networks provide a fundamental framework for understanding the molecular mechanisms 13 that govern gene expression. Advances in single-cell RNA sequencing (scRNA-seq) have enabled 14 network inference at cellular resolution; however, most existing approaches rely on predefined 15 clusters or cell...
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Method: Tree-based differential testing using inferential uncertainty for RNA-seq
- Noor Pratap Singh,
- Euphy Y. Wu,
- Jason Fan,
- Michael I. Love,
- and Rob Patro
Genome Res. October 2025 35: 2326-2338; Published in Advance August 21, 2025, doi:10.1101/gr.279981.124
...-aware differential transcript/gene expression methods. Our method detects inner nodes that show a strong signal for differential expression, which would have been overlooked when analyzing the transcripts alone.RNA-seq has become the de facto technology for measuring the expression profiles of different genomic...
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Method: Bayesian inference of sample-specific coexpression networks
- Enakshi Saha,
- Viola Fanfani,
- Panagiotis Mandros,
- Marouen Ben Guebila,
- Jonas Fischer,
- Katherine H. Shutta,
- Dawn L. DeMeo,
- Camila M. Lopes-Ramos,
- and John Quackenbush
Genome Res. September 2024 34: 1397-1410; Published in Advance August 12, 2024, doi:10.1101/gr.279117.124
...networks is a critical element of GRN inference, as the correlation between expression patterns may indicate that genes are coregulated by common factors. However, methods that estimate coexpression networks generally derive an aggregate network representing the mean regulatory properties of the population...
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Research: Global identification of mammalian host and nested gene pairs reveal tissue-specific transcriptional interplay
- Bertille Montibus,
- James A. Cain,
- Rocio T. Martinez-Nunez,
- and Rebecca J. Oakey
Genome Res. December 2024 34: 2163-2175; Published in Advance November 22, 2024, doi:10.1101/gr.279430.124
...that transcriptional co-occurrence is often tissue specific. This coexpression was especially prevalent within the transcriptionally permissive tissue, testis. We use this developmental system and scRNA-seq analysis to demonstrate that the coexpression of pairs can occur in single cells and transcription in the same...
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Resource: Binding profiles for 961 Drosophila and C. elegans transcription factors reveal tissue-specific regulatory relationships
- Michelle Kudron,
- Louis Gevirtzman,
- Alec Victorsen,
- Bridget C. Lear,
- Jiahao Gao,
- Jinrui Xu,
- Swapna Samanta,
- Emily Frink,
- Adri Tran-Pearson,
- Chau Huynh,
- Dionne Vafeados,
- Ann Hammonds,
- William Fisher,
- Martha Wall,
- Greg Wesseling,
- Vanessa Hernandez,
- Zhichun Lin,
- Mary Kasparian,
- Kevin White,
- Ravi Allada,
- Mark Gerstein,
- LaDeana Hillier,
- Susan E. Celniker,
- Valerie Reinke,
- and Robert H. Waterston
Genome Res. December 2024 34: 2319-2334; Published in Advance October 22, 2024, doi:10.1101/gr.279037.124
...depends on metapeak size and complexity. Combining ChIP-seq data with single-cell RNA-seq data in a machine-learning model identifies TFs with a prominent role in promoting target gene expression in specific cell types, even differentiating between parent–daughter cells during embryogenesis. These data...
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Method: A gene regulatory network–aware graph learning method for cell identity annotation in single-cell RNA-seq data
- Mengyuan Zhao,
- Jiawei Li,
- Xiaoyi Liu,
- Ke Ma,
- Jijun Tang,
- and Fei Guo
Genome Res. July 2024 34: 1036-1051; Published in Advance August 12, 2024, doi:10.1101/gr.278439.123
...of emulating molecular mechanisms in which genes act as “bridges” in biological systems while achieving distantly related cellular communications.Thus, scHGR is a single-cell resolution annotation tool that integrates gene regulatory networks into cell identity inference. For scRNA-seq data sets from various...
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Method: Evaluation of strategies for evidence-driven genome annotation using long-read RNA-seq
- Alejandro Paniagua,
- Cristina Agustín-García,
- Francisco J. Pardo-Palacios,
- Thomas Brown,
- Maite De Maria,
- Nancy D. Denslow,
- Camila J. Mazzoni,
- and Ana Conesa
Genome Res. April 2025 35: 1053-1064; Published in Advance December 23, 2024, doi:10.1101/gr.279864.124
...'s organisms, herald a new era of possibilities and requirements for annotation. Traditionally, annotation has relied on ab initio algorithms alone or combined with short-read sequencing and proteomics data to improve gene predictions. However, with the increased availability and throughput of lrRNA-seq...
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Research: Mapping multitissue regulatory variants reveals a liver-centric coexpression network associated with duck egg-laying performance
- Yang Xi,
- Jingjing Qi,
- Zhao Yang,
- Yutian Zeng,
- Huicong Zhang,
- Qiuyu Tao,
- Mengru Xu,
- Anqi Huang,
- Shenqiang Hu,
- Chunchun Han,
- Lili Bai,
- Jiwei Hu,
- Jiwen Wang,
- Liang Li,
- Lingzhao Fang,
- and Hehe Liu
Genome Res. October 2025 35: 2211-2225; Published in Advance September 10, 2025, doi:10.1101/gr.280345.124
.... That could be attributed to the temporal and tissue specificity of regulatory variations, as such associations have primarily been found in the pituitary gland (Luan et al. 2013; Gao et al. 2015) and our RNA-seq data were only collected at a single time point (330 days old). These results also highlighted...
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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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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
...polyadenylation (APA) plays a crucial role in gene regulation and phenotypic diversity. Whereas extensive studies have explored the global APA landscape using bulk RNA-seq data, in-depth analyses of APA events at the single-cell level remain limited—particularly in farm animals. In this study, we construct...

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