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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
...by 30%–50%. This fine-grained “mutagenesis” can reconstruct functionalized binding motifs for all factors. To prioritize causal variants, we trained a convolutional neural network (Basenji) to accurately predict binding from DNA sequence. The model can also predict measured allelic imbalance for strong...
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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
...transcriptase (Thermo Fisher Scientific) using oligo(dT) primers. The diluted (1/5) total cDNA was subjected to TaqMan gene expression (Thermo Fisher Scientific) using the following transcript-specific probes and primers: RET (Hs01120032_m1), EDNRB (Hs00240747_m1), PAX3(Hs00992437_m1), SOX10 (Hs00366918_m1...
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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
...and environmental conditions. DNA regulatory elements (e.g., promoters and enhancers) are essential to this process by integrating regulatory information from sequence-specific transcription factors (TFs), RNA polymerase II (Pol II), and other regulatory proteins to drive specific spatiotemporal patterns...
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Research: Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal
- Juan L. Mateo,
- Debbie L.C. van den Berg,
- Maximilian Haeussler,
- Daniela Drechsel,
- Zachary B. Gaber,
- Diogo S. Castro,
- Paul Robson,
- Q. Richard Lu,
- Gregory E. Crawford,
- Paul Flicek,
- Laurence Ettwiller,
- Joachim Wittbrodt,
- François Guillemot,
- and Ben Martynoga
Genome Res. January 2015 25: 41-56; Published in Advance October 7, 2014, doi:10.1101/gr.173435.114
...). Upon adenoviral delivery of Cre recombinase, we were able to induce complete depletion of Olig2 transcripts, total protein, and DNA-bound protein within 48 h (Fig. 7A,G; Supplemental Fig. S6). Olig2-deleted cells remained undifferentiated according to morphological criteria and continued to proliferate...
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Method: Sequence-based correction of barcode bias in massively parallel reporter assays
- Dongwon Lee,
- Ashish Kapoor,
- Changhee Lee,
- Michael Mudgett,
- Michael A. Beer,
- and Aravinda Chakravarti
Genome Res. September 2021 31: 1638-1645; Published in Advance July 20, 2021, doi:10.1101/gr.268599.120
..., Crawford GE, Chakravarti A. 2018. Human cardiac cis-regulatory elements, their cognate transcription factors, and regulatory DNA sequence variants. Genome Res 28: 1577–1588. doi:10.1101/gr.234633.118 ↵Maurano MT, Humbert R, Rynes E, Thurman RE, Haugen E, Wang H, Reynolds AP, Sandstrom R, Qu H, Brody J, et...
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Resource: Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
- Bérénice A. Benayoun,
- Elizabeth A. Pollina,
- Param Priya Singh,
- Salah Mahmoudi,
- Itamar Harel,
- Kerriann M. Casey,
- Ben W. Dulken,
- Anshul Kundaje,
- and Anne Brunet
Genome Res. April 2019 29: 697-709; Published in Advance March 11, 2019, doi:10.1101/gr.240093.118
...levels.Interferon response activation can stem from (1) exogenous viral infection, (2) reactivation of endogenous transposable elements (TEs) (De Cecco et al. 2013; Wood and Helfand 2013), and (3) aberrant cytosolic DNA detection by the cyclic GMP-AMP synthase (cGAS) pathway (Sun et al. 2013; West et al...
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Resource: High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues
- Guo-Jen Huang,
- Sagiv Shifman,
- William Valdar,
- Martina Johannesson,
- Binnaz Yalcin,
- Martin S. Taylor,
- Jennifer M. Taylor,
- Richard Mott,
- and Jonathan Flint
Genome Res. June 2009 19: 1133-1140; Published in Advance April 17, 2009, doi:10.1101/gr.088120.108
...was attributable to a large cis -eQTL (percent variation &gt;50). We designed primers to amplify the same exon as that detected by the Illumina array, using primers that hybridized to DNA without annotated SNPs. We then measured transcript abundance in the eight inbred progenitor strains by qPCR and by using...
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Letter: Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts
- Jeremy R. Sanford,
- Xin Wang,
- Matthew Mort,
- Natalia VanDuyn,
- David N. Cooper,
- Sean D. Mooney,
- Howard J. Edenberg,
- and Yunlong Liu
Genome Res. March 2009 19: 381-394; Published in Advance December 30, 2008, doi:10.1101/gr.082503.108
...powerful methodologies used to examine interactions of RNA-binding proteins with their cognate targets is the RNA immunoprecipitation-microarray experiment (RIP-chip). RIP-chip is similar to chromatin IP-microarray analysis (ChIP-chip) with the exception that it is RNA–protein rather than DNA...

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