SEMplMe: a tool for integrating DNA methylation effects in transcription factor binding affinity predictions
Abstract Motivation Aberrant DNA methylation in transcription factor binding sites has been shown to lead to anomalous gene regulation that is strongly associated with human disease. However, the majority of methylation-sensitive positions within transcription factor binding sites remain unknown. He...
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Format: | Article |
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BMC
2022-08-01
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Series: | BMC Bioinformatics |
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Online Access: | https://doi.org/10.1186/s12859-022-04865-x |
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author | Sierra S. Nishizaki Alan P. Boyle |
author_facet | Sierra S. Nishizaki Alan P. Boyle |
author_sort | Sierra S. Nishizaki |
collection | DOAJ |
description | Abstract Motivation Aberrant DNA methylation in transcription factor binding sites has been shown to lead to anomalous gene regulation that is strongly associated with human disease. However, the majority of methylation-sensitive positions within transcription factor binding sites remain unknown. Here we introduce SEMplMe, a computational tool to generate predictions of the effect of methylation on transcription factor binding strength in every position within a transcription factor’s motif. Results SEMplMe uses ChIP-seq and whole genome bisulfite sequencing to predict effects of methylation within binding sites. SEMplMe validates known methylation sensitive and insensitive positions within a binding motif, identifies cell type specific transcription factor binding driven by methylation, and outperforms SELEX-based predictions for CTCF. These predictions can be used to identify aberrant sites of DNA methylation contributing to human disease. Availability and Implementation SEMplMe is available from https://github.com/Boyle-Lab/SEMplMe . |
first_indexed | 2024-04-11T21:36:11Z |
format | Article |
id | doaj.art-cb121f03249d4f25ad302ccd16382a07 |
institution | Directory Open Access Journal |
issn | 1471-2105 |
language | English |
last_indexed | 2024-04-11T21:36:11Z |
publishDate | 2022-08-01 |
publisher | BMC |
record_format | Article |
series | BMC Bioinformatics |
spelling | doaj.art-cb121f03249d4f25ad302ccd16382a072022-12-22T04:01:45ZengBMCBMC Bioinformatics1471-21052022-08-0123111410.1186/s12859-022-04865-xSEMplMe: a tool for integrating DNA methylation effects in transcription factor binding affinity predictionsSierra S. Nishizaki0Alan P. Boyle1Department of Human Genetics, University of MichiganDepartment of Human Genetics, University of MichiganAbstract Motivation Aberrant DNA methylation in transcription factor binding sites has been shown to lead to anomalous gene regulation that is strongly associated with human disease. However, the majority of methylation-sensitive positions within transcription factor binding sites remain unknown. Here we introduce SEMplMe, a computational tool to generate predictions of the effect of methylation on transcription factor binding strength in every position within a transcription factor’s motif. Results SEMplMe uses ChIP-seq and whole genome bisulfite sequencing to predict effects of methylation within binding sites. SEMplMe validates known methylation sensitive and insensitive positions within a binding motif, identifies cell type specific transcription factor binding driven by methylation, and outperforms SELEX-based predictions for CTCF. These predictions can be used to identify aberrant sites of DNA methylation contributing to human disease. Availability and Implementation SEMplMe is available from https://github.com/Boyle-Lab/SEMplMe .https://doi.org/10.1186/s12859-022-04865-xDNA methylationTranscription factorTFBSGene regulationNoncoding variationSoftware |
spellingShingle | Sierra S. Nishizaki Alan P. Boyle SEMplMe: a tool for integrating DNA methylation effects in transcription factor binding affinity predictions BMC Bioinformatics DNA methylation Transcription factor TFBS Gene regulation Noncoding variation Software |
title | SEMplMe: a tool for integrating DNA methylation effects in transcription factor binding affinity predictions |
title_full | SEMplMe: a tool for integrating DNA methylation effects in transcription factor binding affinity predictions |
title_fullStr | SEMplMe: a tool for integrating DNA methylation effects in transcription factor binding affinity predictions |
title_full_unstemmed | SEMplMe: a tool for integrating DNA methylation effects in transcription factor binding affinity predictions |
title_short | SEMplMe: a tool for integrating DNA methylation effects in transcription factor binding affinity predictions |
title_sort | semplme a tool for integrating dna methylation effects in transcription factor binding affinity predictions |
topic | DNA methylation Transcription factor TFBS Gene regulation Noncoding variation Software |
url | https://doi.org/10.1186/s12859-022-04865-x |
work_keys_str_mv | AT sierrasnishizaki semplmeatoolforintegratingdnamethylationeffectsintranscriptionfactorbindingaffinitypredictions AT alanpboyle semplmeatoolforintegratingdnamethylationeffectsintranscriptionfactorbindingaffinitypredictions |