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Method: Recalibrating differential gene expression by genetic dosage variance prioritizes functionally relevant genes
- Philipp Rentzsch,
- Aaron Kollotzek,
- Kaushik Ram Ganapathy,
- Pejman Mohammadi,
- and Tuuli Lappalainen
Genome Res. October 2025 35: 2316-2325; Published in Advance September 17, 2025, doi:10.1101/gr.280360.124
...that this approach will simplify the identification of disease-causing molecular processes and enhance the discovery of therapeutic targets.Since the advent of cDNA microarrays (Schena et al. 1995), differential gene expression profiling has been used to examine the characteristic gene regulatory changes...
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Method: Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease
- Tanner D. Jensen,
- Bohan Ni,
- Chloe M. Reuter,
- John E. Gorzynski,
- Sarah Fazal,
- Devon Bonner,
- Rachel A. Ungar,
- Pagé C. Goddard,
- Archana Raja,
- Euan A. Ashley,
- Jonathan A. Bernstein,
- Stephan Zuchner,
- Undiagnosed Diseases Network,
- Michael D. Greicius,
- Stephen B. Montgomery,
- Michael C. Schatz,
- Matthew T. Wheeler,
- and Alexis Battle
Genome Res. April 2025 35: 914-928; Published in Advance March 20, 2025, doi:10.1101/gr.279323.124
...causal for a rare neurodevelopmental disorder. Our observations demonstrate the promise of integrating long-read sequencing with gene expression toward improving the prioritization of functional SVs and TREs in rare disease patients.Long-read sequencing technology has improved in recent years in terms...
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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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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. April 2026 36: 849-864; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...are downregulated at early aging stages in oligodendrocyte. Our multiomic atlas underscores the substantial regulatory network changes during aging that may predispose to PD, providing valuable insights for furthering understanding of PD pathogenesis and potential therapeutic targets.Parkinson's disease (PD...
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Research: Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
- Benjamin D. Umans and
- Yoav Gilad
Genome Res. August 2025 35: 1689-1700; Published in Advance June 2, 2025, doi:10.1101/gr.280219.124
...between genetic variants and environmental stressors is key to understanding the mechanisms underlying neurological diseases. In this study, we use human brain organoids to explore how varying oxygen levels expose context-dependent gene regulatory effects. By subjecting a genetically diverse panel of 21...
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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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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
...polyploidization as well as changes in calcium dynamics and metabolism following stress with endothelin-1. Collectively, these results identify regulatory mechanisms of cardiac gene programs that modulate cardiomyocyte maturation, affect cellular stress response, and could serve as potential therapeutic targets...
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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
...into contextualized gene regulatory networks (GRNs). In addition, PKNs enable the inference of upstream signaling pathways (USPs) for each CSN by tracing signal transduction paths (receptor–TF–target) inferred based on the contextualized TF–target interactions.By repeating this regression procedure across all...
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Resource: Integrated single-cell multiome analysis reveals muscle fiber-type gene regulatory circuitry modulated by endurance exercise
- Aliza B. Rubenstein,
- Gregory R. Smith,
- Zidong Zhang,
- Xi Chen,
- Toby L. Chambers,
- Frederique Ruf-Zamojski,
- Natalia Mendelev,
- Wan Sze Cheng,
- Michel Zamojski,
- Mary Anne S. Amper,
- Venugopalan D. Nair,
- Andrew R. Marderstein,
- Stephen B. Montgomery,
- Olga G. Troyanskaya,
- Elena Zaslavsky,
- Todd Trappe,
- Scott Trappe,
- and Stuart C. Sealfon
Genome Res. July 2025 35: 1664-1677; Published in Advance May 20, 2025, doi:10.1101/gr.280051.124
...adaptations to exercise, are controlled through the interaction of proximal and distal regulatory domains on DNA that interact in 3D space (Schoenfelder and Fraser 2019). Gene regulatory circuits, comprising chromatin regulatory domains, transcription factors (TFs), and their target genes, represent...
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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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