Dataset Information
A DNA shape-based regulatory score improves position-weight matrix-based recognition of transcription factor binding sites.
Ontology highlight
ABSTRACT: Motivation
The position-weight matrix (PWM) is a useful representation of a transcription factor binding site (TFBS) sequence pattern because the PWM can be estimated from a small number of representative TFBS sequences. However, because the PWM probability model assumes independence between individual nucleotide positions, the PWMs for some TFs poorly discriminate binding sites from non-binding-sites that have similar sequence content. Since the local three-dimensional DNA structure ('shape') is a determinant of TF binding specificity and since DNA shape has a significant sequence-dependence, we combined DNA shape-derived features into a TF-generalized regulatory score and tested whether the score could improve PWM-based discrimination of TFBS from non-binding-sites.Results
We compared a traditional PWM model to a model that combines the PWM with a DNA shape feature-based regulatory potential score, for accuracy in detecting binding sites for 75 vertebrate transcription factors. The PWM+shape model was more accurate than the PWM-only model, for 45% of TFs tested, with no significant loss of accuracy for the remaining TFs.Availability and implementation
The shape-based model is available as an open-source R package at that is archived on the GitHub software repository at https://github.com/ramseylab/regshape/.Contact
stephen.ramsey@oregonstate.eduSupplementary information
Supplementary data are available at Bioinformatics online.
SUBMITTER: Yang J
PROVIDER: S-EPMC4838056 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Publications
A DNA shape-based regulatory score improves position-weight matrix-based recognition of transcription factor binding sites.
Bioinformatics (Oxford, England) 20150630 21
<h4>Motivation</h4>The position-weight matrix (PWM) is a useful representation of a transcription factor binding site (TFBS) sequence pattern because the PWM can be estimated from a small number of representative TFBS sequences. However, because the PWM probability model assumes independence between individual nucleotide positions, the PWMs for some TFs poorly discriminate binding sites from non-binding-sites that have similar sequence content. Since the local three-dimensional DNA structure ('s ...[more]