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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
...Cell type–specific gene regulatory atlas prioritizes drug targets and repurposable medicines in Alzheimer's disease Yunxiao Ren1,2, Ming Hu3,4, Yang E. Li5, Andrew A. Pieper6,7,8,9,10,11, Jeffrey Cummings12 and Feixiong Cheng1,2,4,13 1Cleveland Clinic Genome Center, Cleveland Clinic Research...
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Method: A novel multislice framework for precision 3D spatial domain reconstruction and disease pathology analysis
- Daijun Zhang,
- Ren Qi,
- Xun Lan,
- and Bin Liu
Genome Res. August 2025 35: 1794-1808; Published in Advance July 14, 2025, doi:10.1101/gr.280281.124
...as a multislice joint analysis framework featuring a precorrection mechanism that enables the precise identification of complex spatial domains, advancing disease pathology insights. STMSC assumes that precise three-dimensional (3D) reconstruction is essential for an in-depth investigation of tissue components...
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Method: Inferring disease progression stages in single-cell transcriptomics using a weakly supervised deep learning approach
- Fabien Wehbe,
- Levi Adams,
- Jordan Babadoudou,
- Samantha Yuen,
- Yoon-Seong Kim,
- and Yoshiaki Tanaka
Genome Res. January 2025 35: 135-146; Published in Advance December 2, 2024, doi:10.1101/gr.278812.123
...disease mechanisms in humans. However, individual cells in patient-derived tissues are in different pathological stages, and hence, such cellular variability impedes subsequent differential gene expression analyses. To overcome such a heterogeneity issue, we present a novel deep learning approach, sc...
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Research: Deciphering the largest disease-associated transcript isoforms in the human neural retina with advanced long-read sequencing approaches
- Merel Stemerdink,
- Tabea Riepe,
- Nick Zomer,
- Renee Salz,
- Michael Kwint,
- Jaap Oostrik,
- Raoul Timmermans,
- Barbara Ferrari,
- Stefano Ferrari,
- Alfredo Dueñas Rey,
- Emma Delanote,
- Suzanne E. de Bruijn,
- Hannie Kremer,
- Susanne Roosing,
- Frauke Coppieters,
- Alexander Hoischen,
- Frans P.M. Cremers,
- Peter A.C. ‘t Hoen,
- Erwin van Wijk,
- and Erik de Vrieze
Genome Res. April 2025 35: 725-739; Published in Advance March 4, 2025, doi:10.1101/gr.280060.124
...for Medical Genetics, Ghent University Hospital, Ghent 9000, Belgium; 7Department of Biomolecular Medicine, Ghent University, Ghent 9000, Belgium; 8Department of Pharmaceutics, Ghent University, Ghent 9000, Belgium; 9Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud...
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Method: A somatic hypermutation–based machine learning model stratifies individuals with Crohn's disease and controls
- Modi Safra,
- Lael Werner,
- Ayelet Peres,
- Pazit Polak,
- Naomi Salamon,
- Michael Schvimer,
- Batia Weiss,
- Iris Barshack,
- Dror S. Shouval,
- and Gur Yaari
Genome Res. January 2023 33: 71-79; Published in Advance December 16, 2022, doi:10.1101/gr.276683.122
...et al. 2012). There are two subtypes of IBD: Crohn's disease (CD), in which inflammation can involve any part of the gastrointestinal tract and is transmural, in contrast to ulcerative colitis, in which inflammation is confined to the colon and is considered superficial. Significant progress has been...
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Method: De novo individualized disease modules reveal the synthetic penetrance of genes and inform personalized treatment regimens
- Taylor M. Weiskittel,
- Choong Y. Ung,
- Cristina Correia,
- Cheng Zhang,
- and Hu Li
Genome Res. January 2022 32: 124-134; Published in Advance December 7, 2021, doi:10.1101/gr.275889.121
...of this variability can be captured with patient stratification through disease subtype classification or biomarker testing, but the majority of inter-patient variability remains unexplained (Dagogo-Jack and Shaw 2018). The lack of broadly applicable biomarkers indicates that unique system-level interactions...
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Method: Multimodal single-cell/nucleus RNA sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer's disease
- Jielin Xu,
- Pengyue Zhang,
- Yin Huang,
- Yadi Zhou,
- Yuan Hou,
- Lynn M. Bekris,
- Justin Lathia,
- Chien-Wei Chiang,
- Lang Li,
- Andrew A. Pieper,
- James B. Leverenz,
- Jeffrey Cummings,
- and Feixiong Cheng
Genome Res. October 2021 31: 1900-1912; Published in Advance February 24, 2021, doi:10.1101/gr.272484.120
.... 2017; Habib et al. 2020). For example, disease-associated microglia (DAM) have been identified as a unique microglia subtype associated with AD (Keren-Shaul et al. 2017), and disease-associated astrocytes (DAA) have been identified as becoming increasingly abundant with progression of AD (Habib et al...
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Perspective: Applications of single-cell genomics and computational strategies to study common disease and population-level variation
- Benjamin J. Auerbach,
- Jian Hu,
- Muredach P. Reilly,
- and Mingyao Li
Genome Res. October 2021 31: 1728-1741; doi:10.1101/gr.275430.121
...atherosclerosis (Wirka et al. 2019; Pan et al. 2020), subtype switching of macrophages during pathological cardiac hypertrophy (Ren et al. 2020), the transition of myeloid cells during the progression and regression of kidney disease (Conway et al. 2020), the transition from homeostatic microglia to amyloid...
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Research: DNA methylation epitypes highlight underlying developmental and disease pathways in acute myeloid leukemia
- Brian Giacopelli,
- Min Wang,
- Ada Cleary,
- Yue-Zhong Wu,
- Anna Reister Schultz,
- Maximilian Schmutz,
- James S. Blachly,
- Ann-Kathrin Eisfeld,
- Bethany Mundy-Bosse,
- Sebastian Vosberg,
- Philipp A. Greif,
- Rainer Claus,
- Lars Bullinger,
- Ramiro Garzon,
- Kevin R. Coombes,
- Clara D. Bloomfield,
- Brian J. Druker,
- Jeffrey W. Tyner,
- John C. Byrd,
- and Christopher C. Oakes
Genome Res. May 2021 31: 747-761; Published in Advance March 11, 2021, doi:10.1101/gr.269233.120
...approaches for improved subclassification and understanding of the biology of the disease. Here, we analyzed -wide DNA methylation in 649 AML patients using Illumina arrays and identified a configuration of 13 subtypes (termed “epitypes”) using unbiased clustering. Integration of genetic data revealed...
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Method: Whole-genome analysis of noncoding genetic variations identifies multiscale regulatory element perturbations associated with Hirschsprung disease
- Alexander Xi Fu,
- Kathy Nga-Chu Lui,
- Clara Sze-Man Tang,
- Ray Kit Ng,
- Frank Pui-Ling Lai,
- Sin-Ting Lau,
- Zhixin Li,
- Maria-Mercè Garcia-Barcelo,
- Pak-Chung Sham,
- Paul Kwong-Hang Tam,
- Elly Sau-Wai Ngan,
- and Kevin Y. Yip
Genome Res. November 2020 30: 1618-1632; Published in Advance September 18, 2020, doi:10.1101/gr.264473.120
...Whole- analysis of noncoding genetic variations identifies multiscale regulatory element perturbations associated with Hirschsprung disease Alexander Xi Fu1,9, Kathy Nga-Chu Lui2,9, Clara Sze-Man Tang2,3, Ray Kit Ng4, Frank Pui-Ling Lai2,3, Sin-Ting Lau2,3, Zhixin Li2, Maria-Mercè Garcia-Barcelo2...

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