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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
...aberrations in cell-cycle control. In non-small-cell lung cancer (NSCLC), instability occurs early in tumor growth, resulting in pronounced intratumor heterogeneity, including changes in gene copy number, and whole- doubling (WGD) in ∼75% of tumors. Gene duplication, genetic drift, and selection mediate...
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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
...1 Title 1 Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals 2 conserved gene alterations linked to Parkinson’s disease 3 Running title: Substantia nigra aging linked to Parkinson 4 Kangli Wang1, Weikun Xia1, Yingli Gu1, Songpeng Zu1, Qian Yang2, Maria Luisa Amaral1...
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Method: Predicted protein 3D structures provide essential insights into the genetic architecture underlying phenotypic diversity in maize
- Shuai Wang,
- Merritt Khaipho-Burch,
- Lynn C. Johnson,
- Zachary R. Miller,
- Peter J. Bradbury,
- Doug Speed,
- William J. Allen,
- M. Cinta Romay,
- Jiquan Xue,
- Edward S. Buckler,
- Guillaume P. Ramstein,
- and Baoxing Song
Genome Res. January 2026 36: 214-225; Published in Advance October 31, 2025, doi:10.1101/gr.280514.125
...to those shown in C.To assess our ability to identify candidate causal genes via structure-based PWAS, we inspected associated protein structures encoded by known genes with phenotypes (Supplemental Fig. S14). The predicted protein structure of the transcription factor LIGULELESS1 (encoded by Zm00001eb...
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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
....ResultsWNT activation promotes immature phenotypes in cultured iPSC-CMsTo identify enhancers that regulate gene expression, we used a reproducible and inducible method to drive immature phenotypes in human iPSC-CMs by activating WNT signaling through chemical inhibition of GSK3 (GSK3i) (Mollova et al. 2013; Mills et al...
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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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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
...with disease. Gene-by-environment (GxE) interactions occur when genetic variants influence how individuals respond to specific environmental exposures, leading to interindividual differences in phenotypes, including variability in disease susceptibility. This concept is particularly important in complex...
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Research: Developmental transcriptomics in Pristionchus reveals the environmental responsiveness of a plasticity gene-regulatory network
- Shelley Reich,
- Tobias Loschko,
- Julie Jung,
- Samantha Nestel,
- Ralf J. Sommer,
- and Michael S. Werner
Genome Res. July 2025 35: 1560-1573; Published in Advance June 9, 2025, doi:10.1101/gr.279783.124
...into environmentally sensitive switch genes and downstream genes that execute the decision.Phenotypic plasticity is a widespread phenomenon by which exposure to different environments elicits different phenotypes from the same genotype (Pigliucci 2001; West-Eberhard 2003; DeWitt and Scheiner 2004). In sexually mature...
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Method: Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC
- Byron J. Smith,
- Chunyu Zhao,
- Veronika Dubinkina,
- Xiaofan Jin,
- Liron Zahavi,
- Saar Shoer,
- Jacqueline Moltzau-Anderson,
- Eran Segal,
- and Katherine S. Pollard
Genome Res. May 2025 35: 1247-1260; Published in Advance April 10, 2025, doi:10.1101/gr.279543.124
...characterization of gene products (Zhou et al. 2019). Although we augmented available annotations by leveraging co-occurrence clusters to investigate epistatic and evolutionary relationships between genes, as others have done previously (Minot et al. 2021), laboratory-based characterization is still vital...
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Method: Deciphering context-specific gene programs from single-cell and spatial transcriptomics data with DeCEP
- Lin Li,
- Xianbin Su,
- and Ze-Guang Han
Genome Res. October 2025 35: 2300-2315; Published in Advance August 21, 2025, doi:10.1101/gr.279689.124
...types or states, particularly during development and disease (Cha and Lee 2020). For example, the gene programs of cancer cells within tumor tissue exhibit significant dysfunction compared with those of normal cells (Hanahan 2022). They also display significant plasticity during key processes...
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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
....lappalainen@scilifelab.seAbstractDifferential expression (DE) analysis is a widely used method for identifying genes that are functionally relevant for an observed phenotype or biological response. However, typical DE analysis includes selection of genes based on a threshold of fold change in expression under the implicit assumption that all genes...
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