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Resource: Cell type–specific gene regulatory atlas prioritizes drug targets and repurposable medicines in Alzheimer's disease
- Yunxiao Ren,
- Ming Hu,
- Yang E. Li,
- Andrew A. Pieper,
- Jeffrey Cummings,
- and Feixiong Cheng
Genome Res. March 2026 36: 645-659; Published in Advance January 21, 2026, doi:10.1101/gr.280436.125
...by integrating experimentally validated interactions from multiple public databases, including yeast two-hybrid (Luck et al. 2020), kinase–substrate, signaling, and protein complex data sets, resulting in a comprehensive network of 351,444 interactions among 17,706 proteins. The drug–target network was built...
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Research: Transcriptomic landscape of transposable elements reveals LTR7-PLAAT4 as a potential oncogene and therapeutic target in pancreatic adenocarcinoma
- Meilong Shi,
- Chuanqi Teng,
- Shan Zhang,
- Xiaobo He,
- Lingyun Xu,
- Fengxian Han,
- Rongqi Wen,
- Ganjun Yu,
- Jingwen Liu,
- Yang Feng,
- Yanfeng Wu,
- Yan Ren,
- Gang Jin,
- and Jing Li
Genome Res. February 2026 36: 275-290; Published in Advance January 8, 2026, doi:10.1101/gr.280528.125
...platform and evaluated the correlation between drug sensitivity and LTR7-PLAAT4 status in the organoids. A bespoke 64 compound library was assembled for screening, including chemotherapy (n = 14) and targeted drugs (n = 23) (Supplemental Table S8). As positive controls, one organoid (DAC78) bearing...
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Research: Wnt signaling activation induces CTCF binding and loop formation at cis-regulatory elements of target genes
- Anna Nordin,
- Chaitali Chakraborty,
- Mattias Jonasson,
- Orgena Dano,
- Gianluca Zambanini,
- Pierfrancesco Pagella,
- Silvia Remeseiro,
- and Claudio Cantù
Genome Res. August 2025 35: 1701-1716; Published in Advance June 23, 2025, doi:10.1101/gr.279684.124
...as beta-catenin) drives the expression of target genes from regulatory regions bound by TCF/LEF transcription factors. Gene regulation, however, entails the interplay between sequence information and 3D structure, yet the impact of Wnt signaling on structure has been poorly explored. Here, we investigate...
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Research: Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells
- Marcel Tarbier,
- Sebastian D. Mackowiak,
- Vaishnovi Sekar,
- Franziska Bonath,
- Etka Yapar,
- Bastian Fromm,
- Omid R. Faridani,
- Inna Biryukova,
- and Marc R. Friedländer
Genome Res. February 2026 36: 291-302; Published in Advance January 12, 2026, doi:10.1101/gr.279914.124
...target expression variation and covariation, but these observations have been limited to a few microRNAs. Here we systematically study microRNA alternative functions in mouse embryonic stem cells (mESCs) by genetically deleting Drosha, leading to global loss of microRNAs. We apply complementary single...
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Research: Alternative splicing generates HER2 isoform diversity underlying antibody–drug conjugate resistance in breast cancer
- Gabriela D.A. Guardia,
- Carlos H. dos Anjos,
- Aline Rangel-Pozzo,
- Filipe F. dos Santos,
- Alexander Birbrair,
- Paula F. Asprino,
- Anamaria A. Camargo,
- and Pedro A.F. Galante
Genome Res. September 2025 35: 1942-1958; Published in Advance July 15, 2025, doi:10.1101/gr.280304.124
...of the ERBB2 receptor (also known as HER2) and hormone receptors. Targeted therapies for HER2-positive BC, such as trastuzumab, antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors, have improved patient outcomes, but primary/acquired resistance still poses challenges that can limit treatments’ long...
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Method: Systematic identification of interchromosomal interaction networks supports the existence of specialized RNA factories
- Borislav Hrisimirov Hristov,
- William Stafford Noble,
- and Alessandro Bertero
Genome Res. October 2024 34: 1610-1623; Published in Advance September 25, 2024, doi:10.1101/gr.278327.123
....Loci strongly bound by DNA-binding proteins often exhibit significant interactions in transThe identification of dense subnetworks of trans Hi-C contacts that are enriched for RBM20 targets supports our hypothesis that RNA biogenesis influences 3D chromatin organization by bringing into proximity coregulated...
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Resource: DEAD box RNA helicases are pervasive protein kinase interactors and activators
- Alexander Hirth,
- Edoardo Fatti,
- Eugen Netz,
- Sergio P. Acebron,
- Dimitris Papageorgiou,
- Andrea Švorinić,
- Cristina-Maria Cruciat,
- Emil Karaulanov,
- Alexandr Gopanenko,
- Tianheng Zhu,
- Irmgard Sinning,
- Jeroen Krijgsveld,
- Oliver Kohlbacher,
- and Christof Niehrs
Genome Res. June 2024 34: 952-966; Published in Advance July 10, 2024, doi:10.1101/gr.278264.123
...their role in RNA biology, DDX proteins may stimulate protein kinases. To investigate if protein kinase–DDX interaction is a more widespread phenomenon, we conducted three orthogonal large-scale screens, including proteomics analysis with 32 RNA helicases, protein array profiling, and kinome-wide in vitro...
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Method: Delineating yeast cleavage and polyadenylation signals using deep learning
- Emily Kunce Stroup and
- Zhe Ji
Genome Res. July 2024 34: 1066-1080; Published in Advance June 24, 2024, doi:10.1101/gr.278606.123
....ji@northwestern.eduAbstract3′-end cleavage and polyadenylation is an essential process for eukaryotic mRNA maturation. In yeast species, the polyadenylation signals that recruit the processing machinery are degenerate and remain poorly characterized compared with the well-defined regulatory elements in mammals. Here we...
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Method: Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution
- Qian Qin,
- Victoria Popic,
- Kirsty Wienand,
- Houlin Yu,
- Emily White,
- Akanksha Khorgade,
- Asa Shin,
- Christophe Georgescu,
- Catarina D. Campbell,
- Arthur Dondi,
- Niko Beerenwinkel,
- Francisca Vazquez,
- Aziz M. Al'Khafaji,
- and Brian J. Haas
Genome Res. April 2025 35: 967-986; Published in Advance March 14, 2025, doi:10.1101/gr.279200.124
...the landscape of cancer genomic variations, deriving biomarkers for molecular diagnostics of cancer patients, and targeting therapies such as tyrosine kinase inhibitors for the treatment of kinase gene fusions such as BCR::ABL1 in CML patients (Cuellar et al. 2018) and EML4::ALK (Christopoulos et al. 2018...
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Method: 3′-end ligation sequencing is a sensitive method to detect DNA nicks at potential sites of off-target activity induced by prime editors
- Jacob Stewart-Ornstein,
- Matthew J. Irby,
- Marina K. Lilieholm,
- Dylan Laprise,
- Maria D. Collier,
- Thomas Aunins,
- Dewi Harjanto,
- Aaron N. Chang,
- Deepak Reyon,
- and Jeremy S. Duffield
Genome Res. September 2025 35: 2064-2075; Published in Advance August 5, 2025, doi:10.1101/gr.280164.124
...and have not been widely used for off-target identification (Cao et al 2020; Elacqua et al. 2021). We therefore sought to develop a direct deep sequencing strategy that would utilize single-strand ligation of sequencing adapters to efficiently capture SSBs induced by nicking endonucleases.ResultsTo develop...
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