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...

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Autores principales:	Munazah Andrabi, Andrew Paul Hutchins, Diego Miranda-Saavedra, Hidetoshi Kono, Ruth Nussinov, Kenji Mizuguchi, Shandar Ahmad
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8800033390df4bcba2b6b909927e877e
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spelling	oai:doaj.org-article:8800033390df4bcba2b6b909927e877e2021-12-02T12:32:31ZPredicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences10.1038/s41598-017-03199-62045-2322https://doaj.org/article/8800033390df4bcba2b6b909927e877e2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03199-6https://doaj.org/toc/2045-2322Abstract 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.Munazah AndrabiAndrew Paul HutchinsDiego Miranda-SaavedraHidetoshi KonoRuth NussinovKenji MizuguchiShandar AhmadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	predicting conformational ensembles and genome-wide transcription factor binding sites from dna sequences
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8800033390df4bcba2b6b909927e877e
work_keys_str_mv	AT munazahandrabi predictingconformationalensemblesandgenomewidetranscriptionfactorbindingsitesfromdnasequences AT andrewpaulhutchins predictingconformationalensemblesandgenomewidetranscriptionfactorbindingsitesfromdnasequences AT diegomirandasaavedra predictingconformationalensemblesandgenomewidetranscriptionfactorbindingsitesfromdnasequences AT hidetoshikono predictingconformationalensemblesandgenomewidetranscriptionfactorbindingsitesfromdnasequences AT ruthnussinov predictingconformationalensemblesandgenomewidetranscriptionfactorbindingsitesfromdnasequences AT kenjimizuguchi predictingconformationalensemblesandgenomewidetranscriptionfactorbindingsitesfromdnasequences AT shandarahmad predictingconformationalensemblesandgenomewidetranscriptionfactorbindingsitesfromdnasequences
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Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences

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