Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences
Abstract DNA shape is emerging as an important determinant of transcription factor binding beyond just the DNA sequence. The only tool for large scale DNA shape estimates, DNAshape was derived from Monte-Carlo simulations and predicts four broad and static DNA shape features, Propeller twist, Helica...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-03199-6 |
| _version_ | 1818845712856645632 |
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| author | Munazah Andrabi Andrew Paul Hutchins Diego Miranda-Saavedra Hidetoshi Kono Ruth Nussinov Kenji Mizuguchi Shandar Ahmad |
| author_facet | Munazah Andrabi Andrew Paul Hutchins Diego Miranda-Saavedra Hidetoshi Kono Ruth Nussinov Kenji Mizuguchi Shandar Ahmad |
| author_sort | Munazah Andrabi |
| collection | DOAJ |
| description | Abstract DNA shape is emerging as an important determinant of transcription factor binding beyond just the DNA sequence. The only tool for large scale DNA shape estimates, DNAshape was derived from Monte-Carlo simulations and predicts four broad and static DNA shape features, Propeller twist, Helical twist, Minor groove width and Roll. The contributions of other shape features e.g. Shift, Slide and Opening cannot be evaluated using DNAshape. Here, we report a novel method DynaSeq, which predicts molecular dynamics-derived ensembles of a more exhaustive set of DNA shape features. We compared the DNAshape and DynaSeq predictions for the common features and applied both to predict the genome-wide binding sites of 1312 TFs available from protein interaction quantification (PIQ) data. The results indicate a good agreement between the two methods for the common shape features and point to advantages in using DynaSeq. Predictive models employing ensembles from individual conformational parameters revealed that base-pair opening - known to be important in strand separation - was the best predictor of transcription factor-binding sites (TFBS) followed by features employed by DNAshape. Of note, TFBS could be predicted not only from the features at the target motif sites, but also from those as far as 200 nucleotides away from the motif. |
| first_indexed | 2024-12-19T05:34:01Z |
| format | Article |
| id | doaj.art-8800033390df4bcba2b6b909927e877e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T05:34:01Z |
| publishDate | 2017-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8800033390df4bcba2b6b909927e877e2022-12-21T20:34:10ZengNature PortfolioScientific Reports2045-23222017-06-017111610.1038/s41598-017-03199-6Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequencesMunazah Andrabi0Andrew Paul Hutchins1Diego Miranda-Saavedra2Hidetoshi Kono3Ruth Nussinov4Kenji Mizuguchi5Shandar Ahmad6National Institutes of Biomedical Innovation Health and NutritionDepartment of Biology, Southern University of Science and Technology of ChinaWorld Premier International (WPI) Immunology Frontier Research Center (IFReC), Osaka UniversityMolecular Modeling and Simulation (MMS) Group, National Institutes for Quantum and Radiological Science and TechnologyNational Cancer Institute, Cancer and Inflammation Program, Leidos Biomedical Research, Inc. FrederickNational Institutes of Biomedical Innovation Health and NutritionNational Institutes of Biomedical Innovation Health and NutritionAbstract DNA shape is emerging as an important determinant of transcription factor binding beyond just the DNA sequence. The only tool for large scale DNA shape estimates, DNAshape was derived from Monte-Carlo simulations and predicts four broad and static DNA shape features, Propeller twist, Helical twist, Minor groove width and Roll. The contributions of other shape features e.g. Shift, Slide and Opening cannot be evaluated using DNAshape. Here, we report a novel method DynaSeq, which predicts molecular dynamics-derived ensembles of a more exhaustive set of DNA shape features. We compared the DNAshape and DynaSeq predictions for the common features and applied both to predict the genome-wide binding sites of 1312 TFs available from protein interaction quantification (PIQ) data. The results indicate a good agreement between the two methods for the common shape features and point to advantages in using DynaSeq. Predictive models employing ensembles from individual conformational parameters revealed that base-pair opening - known to be important in strand separation - was the best predictor of transcription factor-binding sites (TFBS) followed by features employed by DNAshape. Of note, TFBS could be predicted not only from the features at the target motif sites, but also from those as far as 200 nucleotides away from the motif.https://doi.org/10.1038/s41598-017-03199-6 |
| spellingShingle | Munazah Andrabi Andrew Paul Hutchins Diego Miranda-Saavedra Hidetoshi Kono Ruth Nussinov Kenji Mizuguchi Shandar Ahmad Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences Scientific Reports |
| title | Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences |
| title_full | Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences |
| title_fullStr | Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences |
| title_full_unstemmed | Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences |
| title_short | Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences |
| title_sort | predicting conformational ensembles and genome wide transcription factor binding sites from dna sequences |
| url | https://doi.org/10.1038/s41598-017-03199-6 |
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