Benchmarking DNA binding affinity models using allele-specific transcription factor binding data.

ABSTRACT: Transcription factors (TFs) bind to DNA in a highly sequence-specific manner. This specificity can manifest itself in vivo at heterozygous loci as a difference in TF occupancy between the two alleles. When applied on a genomic scale, functional genomic assays such as ChIP-seq typically lack the statistical power to detect allele-specific binding (ASB) at the level of individual variants. To address this, we propose a framework for benchmarking sequence-to-affinity models for TF binding in terms of their ability to predict allelic imbalances in ChIP-seq counts. We show that a likelihood function based on an over-dispersed binomial distribution can aggregate evidence for allelic preference across the genome without requiring statistical significance for individual variants. This allow

SUBMITTER: Li X 

PROVIDER: S-EPMC10760129 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature