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bioRxiv · 10.1101/2025.01.17.633399

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

Roskams-Hieter, B.·Almelid, O.·Ponting, C. P.
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Abstract

Human traits vary in part due to genetically-determined change of transcription factor (TF) binding affinity within gene regulatory regions. However, few trait-causal variants or mechanisms are known. Here we propose 1,960 variants as strong candidates for causally altering human traits. They were discovered by baal-nf which uses ChIP-sequencing data to identify allelic imbalance at heterozygous sites ( allele-specific binding sites; ASBs) within affinity-concordant positions within TF- and/or co-factor binding motifs. These variants are evolutionarily conserved, and enriched for trait associations and gene expression QTLs. baal-nf and these high-quality ASBs now allow trait variation due to altered TF binding to be investigated.

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Roskams-Hieter, B., Almelid, O., Ponting, C. P.. 2025-01-21. baal-nf identifies motif-disrupting variants that decrease transcription factor binding affinity. https://doi.org/10.1101/2025.01.17.633399

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