motifbreakR

motifbreakR predicts the effects of genetic variants on transcription factor binding sites by quantifying how much information is gained or lost between alleles at polymorphic or mutated sequences.

Key Features:

• Flexible Scoring Algorithms: motifbreakR provides three algorithms for motif interrogation: a weighted-sum probability matrix, log-probabilities, and a relative entropy-weighted approach.
• Extensive Motif Sources: Users can interrogate genomes with motifs from multiple public sources.
• Variant Compatibility: The package predicts effects for both novel variants and previously described variants in public databases.
• Broad Genome Support: motifbreakR can interrogate any genome curated within Bioconductor, with support for 32 species and 109 genome versions.

Scientific Applications:

• Functional Annotation of GWAS Variants: motifbreakR aids interpretation of germline genetic risk variants residing in non-coding DNA associated with complex diseases.
• Cancer Variant Analysis: The tool supports functional annotation of somatic variation from studies such as The Cancer Genome Atlas (TCGA).
• Transcription Factor Binding Site Assessment: motifbreakR evaluates whether sequences surrounding polymorphisms or mutations within enhancers or promoters represent good matches to transcription factor binding sites.

Methodology:

motifbreakR calculates information gain or loss between alleles by applying user-selected scoring algorithms to compare motif matches at variant positions against reference genome sequences using publicly sourced position weight matrices.