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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
...the reference, such as disease- and trait-associated variants or engineered sequences. Recent work has applied synthetic regulatory genomics to characterized dozens of deletions, inversions, and rearrangements of DNase I hypersensitive sites (DHSs). Here, we use the state-of-the-art model Enformer to predict...
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Research: Functional genomics analysis of developing zebrafish and human endoderm reveals highly conserved cis-regulatory modules acting during vertebrate organogenesis
- Daniela M. Riley,
- Randa Elsayed,
- Mark D. Walsh,
- Simaran Johal,
- Ying Lin,
- Harry Walton,
- Till Bretschneider,
- Sascha Ott,
- and Andrew C. Nelson
Genome Res. April 2026 36: 695-712; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
..., identification of conserved CRMs is often confounded by rearrangement and substitution of TFBSs, leading to similar functional capabilities without deep sequence conservation (for reviews, see Nelson and Wardle 2013; Long et al. 2016; Jindal and Farley 2021). Despite this, comparative genomic analyses indicate...
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Research: Identification and validation of supervariants reveal novel loci associated with human white matter microstructure
- Shiying Wang,
- Ting Li,
- Bingxin Zhao,
- Wei Dai,
- Yisha Yao,
- Cai Li,
- Tengfei Li,
- Hongtu Zhu,
- and Heping Zhang
Genome Res. January 2024 34: 20-33; Published in Advance December 12, 2023, doi:10.1101/gr.277905.123
..., to account for potential multi-SNP effects. We perform supervariant identification and validation to identify loci associated with 22 white matter fractional anisotropy phenotypes derived from diffusion tensor imaging. To increase reproducibility, we use United Kingdom (UK) Biobank White British (n = 30...
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Research: A novel quantitative trait locus implicates Msh3 in the propensity for genome-wide short tandem repeat expansions in mice
- Mikhail O. Maksimov,
- Cynthia Wu,
- David G. Ashbrook,
- Flavia Villani,
- Vincenza Colonna,
- Nima Mousavi,
- Nichole Ma,
- Lu Lu,
- Jonathan K. Pritchard,
- Alon Goren,
- Robert W. Williams,
- Abraham A. Palmer,
- and Melissa Gymrek
Genome Res. May 2023 33: 689-702; Published in Advance May 1, 2023, doi:10.1101/gr.277576.122
...epoch.Mapping quantitative trait loci for STR mutation phenotypesWe wondered whether observed differences in the number and size of mutations across strains could be driven by genetic variation affecting DNA repair or other pathways. To this end, we defined several quantitative phenotypes to summarize...
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Method: Identification of the shortest species-specific oligonucleotide sequences
- Ioannis Mouratidis,
- Maxwell A. Konnaris,
- Nikol Chantzi,
- Candace S.Y. Chan,
- Michail Patsakis,
- Kimonas Provatas,
- Austin Montgomery,
- Fotis A. Baltoumas,
- Congzhou M. Sha,
- Manvita Mareboina,
- Georgios A. Pavlopoulos,
- Dionysios V. Chartoumpekis,
- and Ilias Georgakopoulos-Soares
Genome Res. February 2025 35: 279-295; Published in Advance January 2, 2025, doi:10.1101/gr.280070.124
...for the identification of nucleic quasi-primes and exemplifies their utility for detecting genomic loci that are associated with human-specific traits and that could be potentially important targets in understanding human brain evolution and brain-associated diseases.View larger version: In this window In a new window...
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Research: Identification of the male-specific region on the guppy Y Chromosome from a haplotype-resolved assembly
- Kang Du,
- Oliver Deusch,
- Ilja Bezrukov,
- Christa Lanz,
- Yann Guiguen,
- Margarete Hoffmann,
- Anette Habring,
- Detlef Weigel,
- Manfred Schartl,
- and Christine Dreyer
Genome Res. March 2025 35: 489-498; Published in Advance March 5, 2025, doi:10.1101/gr.279582.124
...). Then the mapping coverage and content of sex-specific SNPs were determined in 50 kb sliding windows using PSASS (https://github.com/SexGenomicsToolkit/PSASS).TE identificationTransposable elements were identified using RepeatModeler2 (Flynn et al. 2020) and RepeatMasker (https://www.repeatmasker.org/). DNA...
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Resource: Comprehensive identification of genomic and environmental determinants of phenotypic plasticity in maize
- Laura E. Tibbs-Cortes,
- Tingting Guo,
- Carson M. Andorf,
- Xianran Li,
- and Jianming Yu
Genome Res. August 2024 34: 1253-1263; Published in Advance September 13, 2024, doi:10.1101/gr.279027.124
...indices, genomic prediction enables accurate performance predictions. Genome-wide association studies (GWASs) detected genetic loci associated with the plastic response to the identified environmental indices for all examined traits. By systematically uncovering the major environmental and genomic factors...
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Research: Functional noncoding SNPs in human endothelial cells fine-map vascular trait associations
- Anu Toropainen,
- Lindsey K. Stolze,
- Tiit Örd,
- Michael B. Whalen,
- Paula Martí Torrell,
- Verena M. Link,
- Minna U. Kaikkonen,
- and Casey E. Romanoski
Genome Res. March 2022 32: 409-424; Published in Advance February 22, 2022, doi:10.1101/gr.276064.121
...variants and their mechanisms of action in relevant biological systems at scale. The identification of functional variants relative to proxy variants in high linkage disequilibrium (LD) presents an additional challenge. Recent studies have begun to map molecular quantitative trait loci (molQTLs) for gene...
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Research: Epstein–Barr virus nuclear antigen 2 extensively rewires the human chromatin landscape at autoimmune risk loci
- Ted Hong,
- Sreeja Parameswaran,
- Omer A. Donmez,
- Daniel Miller,
- Carmy Forney,
- Michael Lape,
- Mariana Saint Just Ribeiro,
- Jun Liang,
- Lee E. Edsall,
- Albert F. Magnusen,
- William Miller,
- Iouri Chepelev,
- John B. Harley,
- Bo Zhao,
- Leah C. Kottyan,
- and Matthew T. Weirauch
Genome Res. December 2021 31: 2185-2198; Published in Advance November 19, 2021, doi:10.1101/gr.264705.120
...also been shown to be increased in the presence of SLE immune complexes (Hagberg et al. 2013), suggesting a possible role for EBNA2 in LY9 gene regulation in lupus.EBNA2 alters chromatin accessibility at thousands of human genomic lociWe examined the impact of EBNA2 on -wide chromatin accessibility...
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Research: A hidden layer of structural variation in transposable elements reveals potential genetic modifiers in human disease-risk loci
- Elisabeth J. van Bree,
- Rita L.F.P. Guimarães,
- Mischa Lundberg,
- Elena R. Blujdea,
- Jimi L. Rosenkrantz,
- Fred T.G. White,
- Josse Poppinga,
- Paula Ferrer-Raventós,
- Anne-Fleur E. Schneider,
- Isabella Clayton,
- David Haussler,
- Marcel J.T. Reinders,
- Henne Holstege,
- Adam D. Ewing,
- Colette Moses,
- and Frank M.J. Jacobs
Genome Res. April 2022 32: 656-670; Published in Advance March 24, 2022, doi:10.1101/gr.275515.121
...variable SVAs (SV-SVAs) in neurological disease–associated loci, and we further associate SV-SVAs to disease-associated SNPs and differential gene expression using luciferase assays and expression quantitative trait loci data. Finally, we genetically deleted SV-SVAs in the BIN1 and CD2AP Alzheimer...
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