motifbreakR

motifbreakR assesses the impact of genetic variants on transcription factor binding in non-coding regions to support functional annotation of variants from GWAS and The Cancer Genome Atlas (TCGA).

Key Features:

• Assessment of Sequence Match Quality: Evaluates whether the sequence surrounding a polymorphism or mutation matches known motifs to assess potential regulatory impact on transcription factor binding.
• Information Gain/Loss Analysis: Quantifies information gained or lost between alleles of a polymorphism to estimate changes in transcription factor binding affinity.
• Algorithmic Flexibility and Extensibility: Implements multiple algorithms to interrogate genomes with motifs sourced from various public databases.
• Prediction of Variant Effects: Predicts effects of novel and previously described variants found in public databases on motif matches and transcription factor binding.
• Integration with Bioconductor: Operates on genomes curated within Bioconductor for integration into Bioconductor-based workflows.

Scientific Applications:

• Functional annotation of GWAS and TCGA variants: Supports interpretation and functional annotation of variants identified through genome-wide association studies (GWAS) and The Cancer Genome Atlas (TCGA).
• Analysis of non-coding regulatory variants: Assesses effects of polymorphisms and mutations within enhancers, promoters, and other non-coding regions on transcription factor binding and gene regulation.
• Elucidation of disease mechanisms: Aids investigation of molecular mechanisms underlying disease susceptibility and progression by linking variants to altered transcription factor binding.
• Translational research for targets and biomarkers: Assists basic and translational studies aimed at identifying potential therapeutic targets or biomarkers by predicting variant effects.

Methodology:

Interrogates genomes with motifs from public databases using multiple algorithms to evaluate sequence match quality and quantify allele-specific information gain or loss, operating on genomes curated in Bioconductor.