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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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Method: Genome-scale identification of cellular pathways required for cell surface recognition
- Sumana Sharma,
- S. Josefin Bartholdson,
- Amalie C.M. Couch,
- Kosuke Yusa,
- and Gavin J. Wright
Genome Res. September 2018 28: 1372-1382; Published in Advance June 18, 2018, doi:10.1101/gr.231183.117
...and C) or technical (D and E) replicate experiments is shown.Genome-scale, cell-based CRISPR-KO screens identify directly interacting receptorsMany extracellular proteins are known to bind HS, and the finding that HS binding in our assay could be additive rather than codependent on other receptors...
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Method: Systematic identification of interchromosomal interaction networks supports the existence of specialized RNA factories
- Borislav Hrisimirov Hristov,
- William Stafford Noble,
- and Alessandro Bertero
Genome Res. October 2024 34: 1610-1623; Published in Advance September 25, 2024, doi:10.1101/gr.278327.123
...and Duan 2019; Zheng and Xie 2019).Most of our current understanding of 3D architecture centers around chromatin folding within individual chromosomes, that is, on intrachromosomal or cis contacts. These contacts give rise to a variety of hierarchical features at different genomic scales, including...
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Resource: Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes
- Guanjue Xiang,
- Xi He,
- Belinda M. Giardine,
- Kathryn J. Isaac,
- Dylan J. Taylor,
- Rajiv C. McCoy,
- Camden Jansen,
- Cheryl A. Keller,
- Alexander Q. Wixom,
- April Cockburn,
- Amber Miller,
- Qian Qi,
- Yanghua He,
- Yichao Li,
- Jens Lichtenberg,
- Elisabeth F. Heuston,
- Stacie M. Anderson,
- Jing Luan,
- Marit W. Vermunt,
- Feng Yue,
- Michael E.G. Sauria,
- Michael C. Schatz,
- James Taylor,
- Berthold Göttgens,
- Jim R. Hughes,
- Douglas R. Higgs,
- Mitchell J. Weiss,
- Yong Cheng,
- Gerd A. Blobel,
- David M. Bodine,
- Yu Zhang,
- Qunhua Li,
- Shaun Mahony,
- and Ross C. Hardison
Genome Res. July 2024 34: 1089-1105; Published in Advance July 1, 2024, doi:10.1101/gr.277950.123
...Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epis Guanjue Xiang1,2,3, Xi He1, Belinda M. Giardine4, Kathryn J. Isaac5, Dylan J. Taylor5, Rajiv C. McCoy5, Camden Jansen4, Cheryl A. Keller4, Alexander Q. Wixom4, April...
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Method: Pooled analysis of radiation hybrids identifies loci for growth and drug action in mammalian cells
- Arshad H. Khan,
- Andy Lin,
- Richard T. Wang,
- Joshua S. Bloom,
- Kenneth Lange,
- and Desmond J. Smith
Genome Res. October 2020 30: 1458-1467; Published in Advance September 2, 2020, doi:10.1101/gr.262204.120
...), as described at http://creativecommons.org/licenses/by-nc/4.0/.References ↵Ahn S, Wang RT, Park CC, Lin A, Leahy RM, Lange K, Smith DJ. 2009. Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids. PLoS Comput Biol 5: e1000407...
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Method: SeqFold: Genome-scale reconstruction of RNA secondary structure integrating high-throughput sequencing data
- Zhengqing Ouyang,
- Michael P. Snyder,
- and Howard Y. Chang
Genome Res. February 2013 23: 377-387; Published in Advance October 11, 2012, doi:10.1101/gr.138545.112
...SeqFold: Genome-scale reconstruction of RNA secondary structure integrating high-throughput sequencing data Zhengqing Ouyang 1 , 2 , 3 , Michael P. Snyder 2 and Howard Y. Chang 1 , 3 1 Howard Hughes Medical Institute and Program...
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Method: Correcting signal biases and detecting regulatory elements in STARR-seq data
- Young-Sook Kim,
- Graham D. Johnson,
- Jungkyun Seo,
- Alejandro Barrera,
- Thomas N. Cowart,
- William H. Majoros,
- Alejandro Ochoa,
- Andrew S. Allen,
- and Timothy E. Reddy
Genome Res. May 2021 31: 877-889; Published in Advance March 15, 2021, doi:10.1101/gr.269209.120
...for clearer visual identification of elements with activating or repressive regulatory effects. For example, a region near the PER1 gene that is well known to have activating regulatory activity in response activation of the glucocorticoid receptor (NR3C1) (Reddy et al. 2012; Johnson et al. 2018) showed much...
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Research: Evolutionary expansion of DNA hypomethylation in the mammalian germline genome
- Jianghan Qu,
- Emily Hodges,
- Antoine Molaro,
- Pascal Gagneux,
- Matthew D. Dean,
- Gregory J. Hannon,
- and Andrew D. Smith
Genome Res. February 2018 28: 145-158; Published in Advance December 19, 2017, doi:10.1101/gr.225896.117
...the evolution of regulatory systems in different species.Existing comparative analyses of mammalian methylomes have increased our understanding of DNA methylation divergence. Methylation states across multiple primate species recapitulate their phylogenetic relationship (Martin et al. 2011), and greater...
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Research: Comprehensive identification and analysis of human accelerated regulatory DNA
- Rachel M. Gittelman,
- Enna Hun,
- Ferhat Ay,
- Jennifer Madeoy,
- Len Pennacchio,
- William S. Noble,
- R. David Hawkins,
- and Joshua M. Akey
Genome Res. September 2015 25: 1245-1255; Published in Advance June 23, 2015, doi:10.1101/gr.192591.115
.... Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population...
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Research: Dissecting the regulatory activity and sequence content of loci with exceptional numbers of transcription factor associations
- Ryne C. Ramaker,
- Andrew A. Hardigan,
- Say-Tar Goh,
- E. Christopher Partridge,
- Barbara Wold,
- Sara J. Cooper,
- and Richard M. Myers
Genome Res. July 2020 30: 939-950; Published in Advance July 2, 2020, doi:10.1101/gr.260463.119
...) that associate with a locus can act as a quantitative predictor of the locus’ regulatory activity and that the activities of loci with large numbers of DAP associations can be disrupted in a predictable manner by altering subsets of putative “driver motifs.”Classically, regulatory loci are thought...
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