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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Main Authors: Sierra S. Nishizaki, Alan P. Boyle
Format: Article
Language:English
Published: BMC 2022-08-01
Series:BMC Bioinformatics
Subjects:
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 .
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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