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| Status |
Public on Feb 24, 2022 |
| Title |
DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers [Drosophila genome-wide UMI-STARR-seq] |
| Organisms |
Drosophila melanogaster; synthetic construct |
| Experiment type |
Other
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| Summary |
Enhancer sequences control gene expression and comprise binding sites (motifs) for different transcription factors (TFs). Despite extensive genetic and computational studies, the relationship between DNA sequence and regulatory activity is poorly understood and enhancer de novo design is considered impossible. Here we built a deep learning model, DeepSTARR, to quantitatively predict the activities of thousands of developmental and housekeeping enhancers directly from DNA sequence in Drosophila melanogaster S2 cells. The model learned relevant TF motifs and higher-order syntax rules, including functionally non-equivalent instances of the same TF motif that are determined by motif-flanking sequence and inter-motif distances. We validated these rules experimentally and demonstrated their conservation in human by testing more than 40,000 wildtype and mutant Drosophila and human enhancers. Finally, we designed and functionally validated synthetic enhancers with desired activities de novo.
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| Overall design |
Genome-wide UMI-STARR-seq was performed in S2 cells using two core promoters each representing housekeeping and developmental transcription programs. All experiments were performed in 2 biological replicates.
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| Contributor(s) |
de Almeida BP, Reiter F, Pagani M, Stark A |
| Citation(s) |
35551305 |
| |
| Submission date |
Sep 10, 2021 |
| Last update date |
May 26, 2022 |
| Contact name |
Bernardo P de Almeida |
| E-mail(s) |
bernardo.almeida@imp.ac.at
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| Organization name |
Research Institute of Molecular Pathology (IMP)
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| Lab |
Stark Lab
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| Street address |
Campus-Vienna-Biocenter 1
|
| City |
Wien |
| ZIP/Postal code |
1030 |
| Country |
Austria |
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| Platforms (3) |
| GPL19604 |
Illumina HiSeq 2500 (synthetic construct) |
| GPL22106 |
NextSeq 550 (Drosophila melanogaster) |
| GPL27609 |
NextSeq 550 (synthetic construct) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE183939 |
DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers |
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| Relations |
| BioProject |
PRJNA762363 |
| SRA |
SRP336576 |
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