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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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Research: Systematic transcriptome analysis associated with physiological and chronological aging in Caenorhabditis elegans
- Seokjin Ham,
- Sieun S. Kim,
- Sangsoon Park,
- Eun Ji E. Kim,
- Sujeong Kwon,
- Hae-Eun H. Park,
- Yoonji Jung,
- and Seung-Jae V. Lee
Genome Res. November/December 2022 32: 2003-2014; Published in Advance November 9, 2022, doi:10.1101/gr.276515.121
.... Corresponding author: seungjaevlee@kaist.ac.krAbstractAging is associated with changes in a variety of biological processes at the transcriptomic level, including gene expression. Two types of aging occur during a lifetime: chronological and physiological aging. However, dissecting the difference between...
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Research: Polycomb misregulation in enterocytes drives tissue decline in the aging Drosophila intestine
- Sarah M. Leichter,
- Kami Ahmad,
- and Steven Henikoff
Genome Res. January 2026 36: 102-114; Published in Advance November 17, 2025, doi:10.1101/gr.281058.125
...genes in old tissue, the genes for histone His2B and for histone His2A increase the most (Fig. 5C,D), suggesting a higher demand for these histones in the aging gut. In yeast, overexpression of core histone genes extends replicative life span, highlighting their potential role in promoting cellular...
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Method: Estimating the size of long tandem repeat expansions from short reads with ScatTR
- Rashid Al-Abri and
- Gamze Gürsoy
Genome Res. December 2025 35: 2701-2713; Published in Advance August 21, 2025, doi:10.1101/gr.280563.125
...was very low (0.047).ScatTR correctly identifies samples with C9orf72 pathogenic repeat expansionsTo further validate the utility of ScatTR, we assessed its ability to estimate the size of a well-characterized pathogenic repeat expansion in C9orf72 gene, a biomarker for familial ALS and frontotemporal...
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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
...aging. These include changes in DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. Collectively, such alterations disrupt gene regulatory networks, leading to transcriptional dysregulation, loss of cellular homeostasis, and increased vulnerability to age-related diseases...
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Research: Optical genome mapping enables accurate testing of large repeat expansions
- Bart van der Sanden,
- Kornelia Neveling,
- Syukri Shukor,
- Michael D. Gallagher,
- Joyce Lee,
- Stephanie L. Burke,
- Maartje Pennings,
- Ronald van Beek,
- Michiel Oorsprong,
- Ellen Kater-Baats,
- Eveline Kamping,
- Alide A. Tieleman,
- Nicol C. Voermans,
- Ingrid E. Scheffer,
- Jozef Gecz,
- Mark A. Corbett,
- Lisenka E.L.M. Vissers,
- Andy Wing Chun Pang,
- Alex Hastie,
- Erik-Jan Kamsteeg,
- and Alexander Hoischen
Genome Res. April 2025 35: 810-823; Published in Advance March 20, 2025, doi:10.1101/gr.279491.124
...of symptoms, and variation in age of onset, which makes identification of the molecular diagnosis challenging (Tankard et al. 2018).All individuals have a certain repeat length at each disease-associated STR locus; however, only once the size of a disease-associated repeat exceeds a certain repeat size...
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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
...occurring in the early stages of the disease and to inform the development of therapeutics aimed at halting AD progression. Additionally, we presented the distribution of limbic-predominant age-related TDP-43 encephalopathy (LATE) stage, apolipoprotein E (APOE) gene carrier status, sex, and age at death...
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Method: Characterizing tandem repeat complexities across long-read sequencing platforms with TREAT and otter
- Niccoló Tesi,
- Alex Salazar,
- Yaran Zhang,
- Sven van der Lee,
- Marc Hulsman,
- Lydian Knoop,
- Sanduni Wijesekera,
- Jana Krizova,
- Anne-Fleur Schneider,
- Maartje Pennings,
- Kristel Sleegers,
- Erik-Jan Kamsteeg,
- Marcel Reinders,
- and Henne Holstege
Genome Res. November 2024 34: 1942-1953; Published in Advance October 15, 2024, doi:10.1101/gr.279351.124
...; Khristich and Mirkin 2020; Stevanovski et al. 2022). For instance, Fragile-X syndrome results from a GGC repeat expansion in the FMR1 gene, with affected individuals having up to 4000 copies compared to <50 in healthy individuals (Yu et al. 1991). Similarly, ALS is caused by an intronic hexa...
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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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Review: Advancing genomic technologies and clinical awareness accelerates discovery of disease-associated tandem repeat sequences
- Terence Gall-Duncan,
- Nozomu Sato,
- Ryan K.C. Yuen,
- and Christopher E. Pearson
Genome Res. January 2022 32: 1-27; Published in Advance December 29, 2021, doi:10.1101/gr.269530.120
...These authors contributed equally to this review. Corresponding author: christopher.pearson@sickkids.caAbstractExpansions of gene-specific DNA tandem repeats (TRs), first described in 1991 as a disease-causing mutation in humans, are now known to cause >60 phenotypes, not just disease, and not only in humans...

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