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Updated: Apr 8, 2026

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
Published on: February 7, 2019
A DNA shape-based regulatory score improves position-weight matrix-based recognition of transcription factor binding
Jichen Yang1, Stephen A Ramsey2
1Department of Biomedical Sciences and.
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.edu
Supplementary Information:
Supplementary data are available at Bioinformatics online.
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