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Resource: A systems view on DNA damage response kinetics in Tetrahymena
- Emily Nischwitz,
- Vivien Schoonenberg,
- Rachel Mullner,
- Albert Fradera-Sola,
- Susanne Zimbelmann,
- Joshua J Smith,
- and Falk Butter
Genome Res. January 28, 2026 gr.281000.125; Published in Advance January 28, 2026, doi:10.1101/gr.281000.125
...24 0 to 8 hours) integrates over 250 paired transcriptome and proteome measurements. We 25 observe upregulation of known DNA repair proteins as well as a global dynamic response of 26 not yet characterized transcripts and proteins. Using artificial neural networks, we classify 27 different expression...
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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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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
...were normalized by the mean of the pre-exercise samples. (C) Network plot reveals the cell-type-specific target genes (blue) of PPARD (orange) identified by the integrated regulatory circuit analysis. Selected GO terms enriched in the target genes are annotated below. (D,E) Log2 fold-change (log2FC...
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Research: Mutational scanning of CRX classifies clinical variants and reveals biochemical properties of the transcriptional effector domain
- James L. Shepherdson,
- David M. Granas,
- Jie Li,
- Zara Shariff,
- Stephen P. Plassmeyer,
- Alex S. Holehouse,
- Michael A. White,
- and Barak A. Cohen
Genome Res. October 2024 34: 1540-1552; Published in Advance September 25, 2024, doi:10.1101/gr.279415.124
...a cell line carrying a synthetic fluorescent CRX transcriptional reporter and a genomic landing pad (LP) system for controlled single-copy expression of variants. We integrated a plasmid library encoding all single amino acid substitution CRX variants into this cell line so that each individual cell...
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Research: Epigenetic drift score captures directional methylation variability and links aging to transcriptional, metabolic, and genetic alterations
- Xiu Fan,
- Qili Qian,
- Wenran Li,
- Tianzi Liu,
- Changqing Zeng,
- Peilin Jia,
- Huandong Lin,
- Xin Gao,
- Li Jin,
- Mingfeng Xia,
- Sijia Wang,
- and Fan Liu
Genome Res. October 2025 35: 2173-2188; Published in Advance August 1, 2025, doi:10.1101/gr.280155.124
...and Schumacher 2024). Understanding and quantifying epigenetic drift may offer novel biomarkers for aging trajectories, disease susceptibility, and therapeutic interventions aimed at mitigating age-associated decline.The etiology of epigenetic drift is multifactorial. Genetic predisposition accounts...
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Research: Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations
- Irene Mei,
- Susanne Nichterwitz,
- Melanie Leboeuf,
- Jik Nijssen,
- Isadora Lenoel,
- Dirk Repsilber,
- Christian S. Lobsiger,
- and Eva Hedlund
Genome Res. September 2025 35: 1975-1991; Published in Advance July 17, 2025, doi:10.1101/gr.279501.124
...-analysis on existing transcriptomic data sets of rodent mutant Sod1 spinal MNs to reveal a general vulnerability code.ResultsTranscriptional regulation of mutant Sod1 or other disease-associated genes does not underlie selective vulnerability among MNsTo retrieve temporal mechanistic insight into the differential...
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Research: Androgen receptor–mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells
- Johannes Hiltunen,
- Laura Helminen,
- Niina Aaltonen,
- Kaisa-Mari Launonen,
- Hanna Laakso,
- Marjo Malinen,
- Einari A. Niskanen,
- Jorma J. Palvimo,
- and Ville Paakinaho
Genome Res. August 2025 35: 1717-1732; Published in Advance June 2, 2025, doi:10.1101/gr.280224.124
...). In particular, enhancer dysfunction is commonly observed in cancers, in which it can drive disease progression through both genetic and epigenetic mechanisms. Although initial studies emphasized the role of DNA mutations within enhancers in tumorigenesis (Sur et al. 2012), cancers can also arise in the absence...
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Research: Functional genomics analysis of developing zebrafish and human endoderm reveals highly conserved cis-regulatory modules acting during vertebrate organogenesis
- Daniela M. Riley,
- Randa Elsayed,
- Mark D. Walsh,
- Simaran Johal,
- Ying Lin,
- Harry Walton,
- Till Bretschneider,
- Sascha Ott,
- and Andrew C. Nelson
Genome Res. March 4, 2026 ; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
...that there are few endoderm-specific CRMs, with many CRMs governing pancreas development also likely acting within the nervous system. Furthermore, these highly conserved CRMs are strongly enriched for binding sites of “neuro-pancreatic” transcription factors governing both pancreas and nervous system development...
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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 transcription factor (TF)–target gene relationships, chromatin accessibility, and genetic variation, this framework aims to elucidate the cell type–specific regulatory mechanisms underlying AD progression, link genetic risk variants to cis-regulatory elements and target genes, and prioritize...
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Resource: Interspecies systems biology links bacterial metabolic pathways to nematode gene expression, chemotaxis behavior, and survival
- Marina Athanasouli,
- Tobias Loschko,
- and Christian Rödelsperger
Genome Res. October 2025 35: 2363-2374; Published in Advance August 5, 2025, doi:10.1101/gr.280848.125
..., highlighting the complexity of cross-kingdom interactions and their impact on host development and disease. These interactions are influenced by the heterogeneity of the gut microbiome, as well as variations in host diet and genetic background, making them challenging to study. In recent years, the nematodes...

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