Representing Transcription Factor Dimer Binding Sites Using Forked-Position Weight Matrices and Forked-Sequence Logos

Current position weight matrices and sequence logos may not be sufficient for accurately modeling transcription factor binding sites recognized by a mixture of homodimer and heterodimer complexes. To address this issue, we developed forkedTF, an R-library that allows the creation of Forked-Position Weight Matrices (FPWM) and Forked-Sequence Logos (F-Logos), which better capture the heterogeneity of TF binding affinities based on interactions and dimerization with other TFs. Furthermore, we have enhanced the standard PWM format by incorporating additional information on co-factor binding and DNA methylation. Precomputed FPWM and F-Logos are made available in the MethMotif 2024 database, thereby providing ready-to-use resources for analyzing TF binding dynamics. Finally, forkedTF is designed to support the TRANSFAC format, which is compatible with most third-party bioinformatics tools that utilize PWMs. The forkedTF R-library is open source and can be accessed on GitHub at https://github.com/benoukraflab/forkedTF.