Whole Genome Regulatory Variant Evaluation for Transcription Factor Binding

Haoyang Zeng , Tatsunori Hashimoto , Daniel D. Kang , David K. Gifford
doi: http://dx.doi.org/10.1101/017392

Contemporary approaches to predict single nucleotide polymorphisms (SNPs) that alter transcription factor binding rely upon the sequence affinity of a transcription factor as represented by its canonical motif. WAVE (Whole-genome regulAtory Variants Evaluation) is a novel method for predicting more general regulatory variants that affect transcription factor binding, including those that fall outside of the canonical motif. WAVE learns a k-mer based generative model of transcription factor binding from ChIP-seq data and scores variants using its generative binding model. The k-mers learned by WAVE capture more sequence feature in transcription factor binding than a motif-based approach alone, including both a transcription factor’s canonical motif as well as associated co-factor motifs. WAVE significantly outperforms motif-based methods in predicting SNPs associated with allele-specific binding.