motifbreakR v2: expanded variant analysis including indels and integrated evidence from transcription factor binding...

Area of Science:

• Bioinformatics
• Computational Biology
• Genomics

Background:

• Transcription factors (TFs) regulate gene expression by binding to specific DNA sequences.
• Genetic variants can alter TF binding sites, potentially disrupting gene regulation.
• Accurate prediction of variant effects on TF binding is crucial for understanding disease mechanisms.

Purpose of the Study:

• To update and enhance the motifbreakR R package for analyzing the impact of genetic variants on TF binding.
• To expand motifbreakR's capability to include complex genetic variants beyond single nucleotide polymorphisms.
• To improve the accuracy and interpretability of TF binding disruption predictions.

Main Methods:

• Utilizing position weight matrices (PWMs) of TFs to scan genetic variants.
• Incorporating Bioconductor resources for genome and motif annotations.
• Expanding variant analysis to include short insertions and deletions (indels).
• Integrating DNA-binding sequencing data, specifically querying the ReMap2022 database.
• Developing an R/Shiny graphical user interface (GUI) for enhanced accessibility.

Main Results:

• motifbreakR v2 now supports the analysis of complex genetic variants (insertions, deletions) impacting TF binding.
• Integration of TF binding data from ReMap2022 provides experimental validation for predicted binding events.
• The new R/Shiny interface simplifies the use of motifbreakR for researchers.
• Improved confidence in motif disruption predictions through combined sequence-based and experimental data.

Conclusions:

• motifbreakR v2 offers a robust and versatile tool for assessing the functional impact of genetic variants on TF binding.
• The enhanced functionality and user-friendly interface facilitate broader application in genomic research.
• This tool aids in identifying regulatory variants associated with various biological processes and diseases.