# baal-nf identifies motif-disrupting variants that decrease transcription factor binding affinity

## TL;DR

This paper introduces a new method called baal-nf to find genetic variants that affect how transcription factors bind to DNA, potentially influencing human traits.

## Contribution

The novel contribution is the development of baal-nf and the identification of 1,935 candidate variants that may alter transcription factor binding affinity.

## Key findings

- baal-nf identifies allele-specific binding sites that are evolutionarily conserved.
- The identified variants are enriched for associations with traits and gene expression.
- The method provides high-quality candidates for studying trait variation due to transcription factor binding.

## Abstract

Human traits vary in part due to genetically-determined change of transcription factor binding affinity within gene regulatory regions. However, few trait-causal variants or mechanisms are known. Here we propose 1,935 variants as strong candidates for causally altering human traits. We discover these through baal-nf which uses chromatin immunoprecipitation-sequencing data to identify allelic imbalance at heterozygous sites for affinity-concordant positions within transcription factor- and co-factor binding motifs. These allele-specific binding sites are evolutionarily conserved and enriched for trait and gene expression associations. baal-nf and these high-quality allele-specific binding sites allow trait variation due to altered transcription factor binding to be investigated.

The online version contains supplementary material available at 10.1186/s13059-025-03916-9.