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Method: Iterative improvement of deep learning models using synthetic regulatory genomics
- André M. Ribeiro-dos-Santos and
- Matthew T. Maurano
Genome Res. November 2025 35: 2539-2549; Published in Advance October 22, 2025, doi:10.1101/gr.280540.125
...and ultimately enable functional classification of regulatory variants identified by population studies.Most genetic associations with human diseases and traits lie within noncoding regulatory DNA (Maurano et al. 2012). Genome-scale methods to analyze the function of noncoding regulatory elements within...
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Research: Expanded methylome and quantitative trait loci detection by long-read profiling of personal DNA
- Cristian Groza,
- Bing Ge,
- Warren A. Cheung,
- Tomi Pastinen,
- and Guillaume Bourque
Genome Res. April 2025 35: 644-652; Published in Advance March 20, 2025, doi:10.1101/gr.279240.124
...elements, and tandem repeats. More generally, the DNA sequences omitted from current reference s are likely a source of substantial epigenetic activity. Expanding the nonreference results to a larger number of human s and epis can expose population variation with potential new insights on trait variation...
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Method: Scalable cell-specific coexpression networks for granular regulatory pattern discovery with NeighbourNet
- Yidi Deng,
- Jiadong Mao,
- Jarny Choi,
- and Kim-Anh Le Cao
Genome Res. March 5, 2026 gr.281171.125; Published in Advance March 5, 2026, doi:10.1101/gr.281171.125
...1Scalable cell-specific coexpression networks for granular regulatory 2 pattern discovery with NeighbourNet 3 Yidi Deng1,2, Jiadong Mao1,† & Jarny Choi3,† & Kim-Anh Lê Cao1,*,† 4 1Melbourne Integrative Genomics, School of Mathematics and Statistics, The University of Melbourne, 5 3010, Australia 6...
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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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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
...to be a promising approach toward modeling the role of genomic variants in cis regulatory logic. In particular, CNNs have already shown great promise in modeling the contribution of promoter genetic variation on mean gene expression levels. Agarwal and Shendure (2020) first introduced their algorithm, Xpresso...
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Research: Lake Malawi cichlid pangenome graph reveals extensive structural variation driven by transposable elements
- Fu Xiang Quah,
- Miguel Vasconcelos Almeida,
- Moritz Blumer,
- Chengwei Ulrika Yuan,
- Bettina Fischer,
- Kirsten See,
- Ben Jackson,
- Richard Zatha,
- Bosco Rusuwa,
- George F. Turner,
- M. Emília Santos,
- Hannes Svardal,
- Martin Hemberg,
- Richard Durbin,
- and Eric Miska
Genome Res. May 2025 35: 1094-1107; Published in Advance April 10, 2025, doi:10.1101/gr.279674.124
...seven species, the total size of which is 33.1% longer than that of a single cichlid . Approximately 4.73% to 9.86% of the assembly lengths are estimated as interspecies structural variation between cichlids, suggesting substantial genomic diversity underappreciated in SNP studies. Although coding...
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Research: Cis-acting variation is common across regulatory layers but is often buffered during embryonic development
- Swann Floc'hlay,
- Emily S. Wong,
- Bingqing Zhao,
- Rebecca R. Viales,
- Morgane Thomas-Chollier,
- Denis Thieffry,
- David A. Garfield,
- and Eileen E.M. Furlong
Genome Res. February 2021 31: 211-224; Published in Advance December 11, 2020, doi:10.1101/gr.266338.120
...accessibility, histone modifications, and gene expression in F1 embryos generated from eight Drosophila crosses at three embryonic stages, yielding a comprehensive data set of 240 samples spanning multiple regulatory layers. Genetic variation (allelic imbalance) impacts gene expression more frequently than...
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Research: Machine learning identifies activation of RUNX/AP-1 as drivers of mesenchymal and fibrotic regulatory programs in gastric cancer
- Milad Razavi-Mohseni,
- Weitai Huang,
- Yu A. Guo,
- Dustin Shigaki,
- Shamaine Wei Ting Ho,
- Patrick Tan,
- Anders J. Skanderup,
- and Michael A. Beer
Genome Res. May 2024 34: 680-695; Published in Advance May 22, 2024, doi:10.1101/gr.278565.123
...-seq data from a collection of 25 cell lines (Ho et al. 2023). Principal component analysis (PCA) of variation in the activity of distal peaks (Methods) showed significant heterogeneity in chromatin accessibility across the cell lines, forming three clusters (Fig. 1A) with similar genomic accessibility...
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Method: Predicting genotype-specific gene regulatory networks
- Deborah Weighill,
- Marouen Ben Guebila,
- Kimberly Glass,
- John Quackenbush,
- and John Platig
Genome Res. March 2022 32: 524-533; Published in Advance February 22, 2022, doi:10.1101/gr.275107.120
...expression data—provided there are expression and eQTL data from a relevant cell type obtained from a sufficiently large population to infer accurate regulatory network models. This implies that EGRET can be used in interpreting disease-linked variation where the variant colocalizes with an eQTL signal...
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Resource: Impact of regulatory variation across human iPSCs and differentiated cells
- Nicholas E. Banovich,
- Yang I. Li,
- Anil Raj,
- Michelle C. Ward,
- Peyton Greenside,
- Diego Calderon,
- Po Yuan Tung,
- Jonathan E. Burnett,
- Marsha Myrthil,
- Samantha M. Thomas,
- Courtney K. Burrows,
- Irene Gallego Romero,
- Bryan J. Pavlovic,
- Anshul Kundaje,
- Jonathan K. Pritchard,
- and Yoav Gilad
Genome Res. January 2018 28: 122-131; Published in Advance December 5, 2017, doi:10.1101/gr.224436.117
...variation in the population when learning the model parameters.To identify transcription factors that help predict the shared and cell-type–specific regulatory activity across loci, we computed DeepLIFT scores (Shrikumar et al. 2016) with respect to each filter in the first convolutional layer. Among 1320...
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