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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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Method: The oligogenic inheritance test GCOD detects risk genes and their interactions in congenital heart defects
- Maureen Pittman,
- Kihyun Lee,
- Franco Felix,
- Yu Huang,
- Adrienne Lam,
- Mauro W. Costa,
- Deepak Srivastava,
- and Katherine S. Pollard
Genome Res. February 2026 36: 330-347; Published in Advance December 12, 2025, doi:10.1101/gr.281141.125
...target sets, hallmark gene sets, or GO sets (Supplemental Fig. 4).Significant co-occurrence within protein–protein interactions and canonical pathways indicates that the interaction (direct or indirect) of oligogenic set gene products could be relevant to disease pathogenesis. We noted a particularly...
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Resource: Genetic features and genomic targets of human KRAB-zinc finger proteins
- Jonas de Tribolet-Hardy,
- Christian W. Thorball,
- Romain Forey,
- Evarist Planet,
- Julien Duc,
- Alexandre Coudray,
- Bara Khubieh,
- Sandra Offner,
- Cyril Pulver,
- Jacques Fellay,
- Michael Imbeault,
- Priscilla Turelli,
- and Didier Trono
Genome Res. August 2023 33: 1409-1423; Published in Advance September 20, 2023, doi:10.1101/gr.277722.123
...and combinatorial modes of action with strong influences on human speciation.Krüppel-associated box (KRAB) domain-containing zinc finger proteins (KZFPs) constitute one of the largest groups of transcription factors encoded by tetrapods, with 378 protein-coding representatives in human alone (Supplemental Table S1...
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Research: Combinatorial microRNA activity is essential for the transition of pluripotent cells from proliferation into dormancy
- Dhanur P. Iyer,
- Lambert Moyon,
- Lars Wittler,
- Chieh-Yu Cheng,
- Francisca R. Ringeling,
- Stefan Canzar,
- Annalisa Marsico,
- and Aydan Bulut-Karslioğlu
Genome Res. April 2024 34: 572-589; Published in Advance May 6, 2024, doi:10.1101/gr.278662.123
..., the pluripotent epiblast depends on miRNA activity, the absence of which results in the loss of pluripotent cells. Through the integration of high-sensitivity small RNA expression profiling of individual embryos and protein expression of miRNA targets with public data of protein–protein interactions, we...
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Method: Modeling gene interactions in polygenic prediction via geometric deep learning
- Han Li,
- Jianyang Zeng,
- Michael P. Snyder,
- and Sai Zhang
Genome Res. January 2025 35: 178-187; Published in Advance November 19, 2024, doi:10.1101/gr.279694.124
...is a protein-coding gene and each edge stands for an interaction between genes vi and vj with a STRING score greater than 0.8. Note that we add a self-loop (vi, vi) to each node in the network. Finally, we obtain a GGI network encompassing 19,836 genes and 250,236 interactions.PRS-NetGraph neural network...
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Research: Characterization of DNA methylation reader proteins in Arabidopsis thaliana
- Jonathan Cahn,
- James P.B. Lloyd,
- Ino D. Karemaker,
- Pascal W.T.C. Jansen,
- Jahnvi Pflueger,
- Owen Duncan,
- Jakob Petereit,
- Ozren Bogdanovic,
- A. Harvey Millar,
- Michiel Vermeulen,
- and Ryan Lister
Genome Res. December 2024 34: 2229-2243; Published in Advance December 4, 2024, doi:10.1101/gr.279379.124
...by the presence of mCG, irrespective of whether it is a protein-coding gene or TE, and of whether it is expressed or not (Fig. 3). MBD5 and MBD6 bound regions are often cobound by MBD2 (78%), but only in protein-coding regions (Fig. 3A). Genes with body methylation are the main targets of MBD2 identified...
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Method: ERC2.0 evolutionary rate covariation update improves inference of functional interactions across large phylogenies
- Jordan H. Little,
- Guillermo Hoffmann Meyer,
- Aakash Grover,
- Alex Michael Francette,
- Raghavendran Partha,
- Karen M. Arndt,
- Martin Smith,
- Nathan Clark,
- and Maria Chikina
Genome Res. September 2025 35: 2041-2051; Published in Advance August 7, 2025, doi:10.1101/gr.280586.125
...predictions.The omics era has greatly increased the number of sequenced s (Hotaling et al. 2021). With this influx of information, network and system biologists have developed approaches to study gene and protein interactions from a broader perspective and at a much larger scale. Networks of such interactions...
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Research: Enhancers display constrained sequence flexibility and context-specific modulation of motif function
- Franziska Reiter,
- Bernardo P. de Almeida,
- and Alexander Stark
Genome Res. March 2023 33: 346-358; Published in Advance March 20, 2023, doi:10.1101/gr.277246.122
...motifs at different enhancer positions depend on their interaction with other TFs and the sequence context.In summary, testing thousands of sequence variants in different enhancer positions revealed that enhancer sequences display constrained flexibility, in that only a specific but still diverse set...
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Method: Harnessing agent-based frameworks in CellAgentChat to unravel cell–cell interactions from single-cell and spatial transcriptomics
- Vishvak Raghavan,
- Yumin Zheng,
- Yue Li,
- and Jun Ding
Genome Res. July 2025 35: 1646-1663; Published in Advance May 2, 2025, doi:10.1101/gr.279771.124
...at both individual cell and system levels. Moreover, CellAgentChat enables in silico perturbation analysis of the downstream effects of cellular interactions on gene expression, facilitating the identification of potential therapeutic receptor targets. Notably, the adaptive framework of Cell...
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Resource: Single-nucleus transcriptomic mapping uncovers targets for traumatic brain injury
- Qiuyun Yang,
- Lingxuan Zhang,
- Manrui Li,
- Yang Xu,
- Xiaogang Chen,
- Ruixuan Yuan,
- Xiaofeng Ou,
- Min He,
- Miao Liao,
- Lin Zhang,
- Hao Dai,
- Meili Lv,
- Xiaoqi Xie,
- Weibo Liang,
- and Xiameng Chen
Genome Res. October 2023 33: 1818-1832; Published in Advance September 20, 2023, doi:10.1101/gr.277881.123
...) SCENIC results of the control and mTBI group. Major regulators were shown; their corresponding enriched DNA-binding motifs are shown in right column. (F) Ridge plot showing the expression of Tcf7l1. (G) Protein–protein interaction (PPI) networks of TFs and miRNAs in neuroblast (upper) and astrocyte, q...

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