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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
...-precision gene expression analysis techniques across different brain regions can deepen our understanding of how genes regulate brain development and disease processes on structural and functional levels.To assess the impact of the microenvironmental deconstruction module on spatial domain identification...
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Resource: Global compositional and functional states of the human gut microbiome in health and disease
- Sunjae Lee,
- Theo Portlock,
- Emmanuelle Le Chatelier,
- Fernando Garcia-Guevara,
- Frederick Clasen,
- Florian Plaza Oñate,
- Nicolas Pons,
- Neelu Begum,
- Azadeh Harzandi,
- Ceri Proffitt,
- Dorines Rosario,
- Stefania Vaga,
- Junseok Park,
- Kalle von Feilitzen,
- Fredric Johansson,
- Cheng Zhang,
- Lindsey A. Edwards,
- Vincent Lombard,
- Franck Gauthier,
- Claire J. Steves,
- David Gomez-Cabrero,
- Bernard Henrissat,
- Doheon Lee,
- Lars Engstrand,
- Debbie L. Shawcross,
- Gordon Proctor,
- Mathieu Almeida,
- Jens Nielsen,
- Adil Mardinoglu,
- David L. Moyes,
- Stanislav Dusko Ehrlich,
- Mathias Uhlen,
- and Saeed Shoaie
Genome Res. June 2024 34: 967-978; Published in Advance July 22, 2024, doi:10.1101/gr.278637.123
...and statistical methods, we identified Fusobacterium nucleatum and Anaerostipes hadrus with the highest frequencies, enriched and depleted, respectively, across different disease cohorts. Distinct functional distributions were observed in the gut microbiomes of both westernized and nonwesternized populations...
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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
...disease activity is recapitulated in the cohort disease modules, there are additional unexplored interactions detectable only at the individual patient level, which dictate patient-specific mechanisms, phenotypes, and therapeutic responses. We additionally suspect that at the gene level, there are patient...
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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
...discovery slowed as the limitations of technological methods reduced the ability to detect more complex pathogenic repeat expansions. However, recent technological advances in both DNA sequencing techniques and computational analysis have again increased speed of discovery, with 17 new disease...
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Research: A multi-enhancer RET regulatory code is disrupted in Hirschsprung disease
- Sumantra Chatterjee,
- Kameko M. Karasaki,
- Lauren E. Fries,
- Ashish Kapoor,
- and Aravinda Chakravarti
Genome Res. December 2021 31: 2199-2208; Published in Advance November 15, 2021, doi:10.1101/gr.275667.121
...disease risk at a single gene. It is now well established that most human complex traits and diseases arise from the additive genetic effects of hundreds to thousands of variants distributed across the ( Visscher et al. 2017 ). At each locus, multiple statistically significant variants are detected...
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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
...imbalance, as is performed in BSCET (Fan et al. 2021); or detect cell type–interacting QTLs (Donovan et al. 2020; Kim-Hellmuth et al. 2020) or cell composition QTLs (Park et al. 2021). The estimated cell type proportions can also be used to compare cell type compositions between diseased cases and controls...
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Method: Deep profiling and custom databases improve detection of proteoforms generated by alternative splicing
- Laura M. Agosto,
- Matthew R. Gazzara,
- Caleb M. Radens,
- Simone Sidoli,
- Josue Baeza,
- Benjamin A. Garcia,
- and Kristen W. Lynch
Genome Res. December 2019 29: 2046-2055; Published in Advance November 14, 2019, doi:10.1101/gr.248435.119
...database trained on analysis of RNA-seq data with MAJIQ, an algorithm optimized to detect and quantify differential and unannotated splice junction usage. We matched tandem mass spectra acquired by data-dependent acquisition (DDA) against our custom RNA-seq based database, as well as SWISS-PROT and Ref...
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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
...-associated perturbations of regulatory elements, genes, and pathways. Applying it to our whole- sequencing data of 918 short-segment Hirschsprung disease patients and matched controls, we identify various novel genes not detected by standard single-variant and region-based tests, functionally centering on neural crest...
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Perspective: Genomic approaches for understanding the genetics of complex disease
- William L. Lowe, Jr. and
- Timothy E. Reddy
Genome Res. October 2015 25: 1432-1441; doi:10.1101/gr.190603.115
...be used to improve the prediction of disease onset and the design of prevention and early detection strategies. Subsequently determining the effects of causal variants on gene expression can prioritize downstream efforts to characterize causal genes and their role in disease etiology. That prioritization...
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