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Research: Integrating genetic variation with deep learning provides context for variants impacting transcription factor binding during embryogenesis
- Olga M. Sigalova,
- Mattia Forneris,
- Frosina Stojanovska,
- Bingqing Zhao,
- Rebecca R. Viales,
- Adam Rabinowitz,
- Fayrouz Hammal,
- Benoît Ballester,
- Judith B. Zaugg,
- and Eileen E.M. Furlong
Genome Res. May 2025 35: 1138-1153; Published in Advance April 15, 2025, doi:10.1101/gr.279652.124
...can also bind to low-affinity sites or to alternative motifs (Sandmann et al. 2007; Farley et al. 2016; Kribelbauer et al. 2019), we applied ProBound (Rube et al. 2022), a method to predict TF binding affinity based on equilibrium binding, to the sequences ±30 bp around each variant. This indicates...
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Method: Discriminative prediction of mammalian enhancers from DNA sequence
- Dongwon Lee,
- Rachel Karchin,
- and Michael A. Beer
Genome Res. December 2011 21: 2167-2180; Published in Advance August 29, 2011, doi:10.1101/gr.121905.111
...concern in this paper is to identify which sequence features are specific to enhancers and to investigate the degree to which we can identify functional enhancer regions in a mammalian using only DNA sequence features in these regions. We initially focus on recent -wide experiments that identified EP300...
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Method: Multiplexed massively parallel SELEX for characterization of human transcription factor binding specificities
- Arttu Jolma,
- Teemu Kivioja,
- Jarkko Toivonen,
- Lu Cheng,
- Gonghong Wei,
- Martin Enge,
- Mikko Taipale,
- Juan M. Vaquerizas,
- Jian Yan,
- Mikko J. Sillanpää,
- Martin Bonke,
- Kimmo Palin,
- Shaheynoor Talukder,
- Timothy R. Hughes,
- Nicholas M. Luscombe,
- Esko Ukkonen,
- and Jussi Taipale
Genome Res. June 2010 20: 861-873; Published in Advance April 8, 2010, doi:10.1101/gr.100552.109
...and transcriptional activation. The ultimate aim here is to read the genetic code of gene expression, that is, to understand the expression of genes based on DNA sequence. Preparation of high-quality physical models of DNA–DBD interactions using existing methods is laborious and expensive. Economic and relatively...
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Research: Revisiting chromatin packaging in mouse sperm
- Qiangzong Yin,
- Chih-Hsiang Yang,
- Olga S. Strelkova,
- Jingyi Wu,
- Yu Sun,
- Sneha Gopalan,
- Liyan Yang,
- Job Dekker,
- Thomas G. Fazzio,
- Xin Zhiguo Li,
- Johan Gibcus,
- and Oliver J. Rando
Genome Res. December 2023 33: 2079-2093; Published in Advance December 21, 2023, doi:10.1101/gr.277845.123
...IP-seq, and native MNase ChIP-seq. However, each of these assays shows distinct behavior following DNase or DTT treatment; together, these findings raise substantial concerns regarding affinity-based chromatin analysis in bona fide sperm and motivate continued optimization to allow more efficient recovery...
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Method: A unified model for yeast transcript definition
- Carl G. de Boer,
- Harm van Bakel,
- Kyle Tsui,
- Joyce Li,
- Quaid D. Morris,
- Corey Nislow,
- Jack F. Greenblatt,
- and Timothy R. Hughes
Genome Res. January 2014 24: 154-166; Published in Advance October 29, 2013, doi:10.1101/gr.164327.113
...Abstract Identifying genes in the genomic context is central to a cell's ability to interpret the genome. Yet, in general, the signals used to define eukaryotic genes are poorly described. Here, we derived simple classifiers that identify where transcription will initiate and terminate using nucleic acid...
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Method: Predicting cell-type–specific gene expression from regions of open chromatin
- Anirudh Natarajan,
- Galip Gürkan Yardımcı,
- Nathan C. Sheffield,
- Gregory E. Crawford,
- and Uwe Ohler
Genome Res. September 2012 22: 1711-1722; doi:10.1101/gr.135129.111
...Carolina 27708, USA; 4 Department of Biostatistics &amp; Bioinformatics, Duke University, Durham, North Carolina 27708, USA Abstract Complex patterns of cell-type–specific gene expression are thought to be achieved by combinatorial binding of transcription factors (TFs) to sequence...
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Resource: Genome-wide annotation of microRNA primary transcript structures reveals novel regulatory mechanisms
- Tsung-Cheng Chang,
- Mihaela Pertea,
- Sungyul Lee,
- Steven L. Salzberg,
- and Joshua T. Mendell
Genome Res. September 2015 25: 1401-1409; Published in Advance August 19, 2015, doi:10.1101/gr.193607.115
...F, Jensen ST, Ohler U, Hatzigeorgiou AG. 2009. A transcription factor affinity-based code for mammalian transcription initiation. Genome Res 19: 644–656. Melamed Z, Levy A, Ashwal-Fluss R, Lev-Maor G, Mekahel K, Atias N, Gilad S, Sharan R, Levy C, Kadener S, et al. 2013. Alternative splicing...
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Research: Nascent RNA sequencing reveals a dynamic global transcriptional response at genes and enhancers to the natural medicinal compound celastrol
- Noah Dukler,
- Gregory T. Booth,
- Yi-Fei Huang,
- Nathaniel Tippens,
- Colin T. Waters,
- Charles G. Danko,
- John T. Lis,
- and Adam Siepel
Genome Res. November 2017 27: 1816-1829; Published in Advance October 12, 2017, doi:10.1101/gr.222935.117
...affinity based on the DNA sequence alone (Alipanahi et al. 2015). In both cases, we considered the interval between 500 bp upstream of and 200 bp downstream from the transcription start site of each active gene. Our regression model included a coefficient for each TF at each time point. A positive estimate...
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Method: Systematic elucidation and in vivo validation of sequences enriched in hindbrain transcriptional control
- Grzegorz M. Burzynski,
- Xylena Reed,
- Leila Taher,
- Zachary E. Stine,
- Takeshi Matsui,
- Ivan Ovcharenko,
- and Andrew S. McCallion
Genome Res. November 2012 22: 2278-2289; Published in Advance July 3, 2012, doi:10.1101/gr.139717.112
...of enhancers active in various tissues; however, not all enhancers are captured by affinity-based methods, and not all cell types are amenable to these assays. Recent efforts to identify sequence motifs (active TFBS) have proven increasingly powerful, allowing the elucidation of early language structure...
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Research: Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants
- Metewo Selase Enuameh,
- Yuna Asriyan,
- Adam Richards,
- Ryan G. Christensen,
- Victoria L. Hall,
- Majid Kazemian,
- Cong Zhu,
- Hannah Pham,
- Qiong Cheng,
- Charles Blatti,
- Jessie A. Brasefield,
- Matthew D. Basciotta,
- Jianhong Ou,
- Joseph C. McNulty,
- Lihua J. Zhu,
- Susan E. Celniker,
- Saurabh Sinha,
- Gary D. Stormo,
- Michael H. Brodsky,
- and Scot A. Wolfe
Genome Res. June 2013 23: 928-940; Published in Advance March 7, 2013, doi:10.1101/gr.151472.112
...Abstract Cys 2 -His 2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step...

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