MAGGIE: leveraging genetic variation to identify DNA sequence motifs mediating transcription factor binding and function

• DOI: 10.1093/bioinformatics/btaa476
• Publication Date: 2020-05-05T19:19:51Z
• Authors: Zeyang Shen; Marten A Hoeksema; Zhengyu Ouyang; Christopher Benner; Christopher K Glass
• Keywords: Motif (music); Sequence motif; DNA binding site

Abstract Motivation Genetic variation in regulatory elements can alter transcription factor (TF) binding by mutating a TF motif, which turn may affect the activity of elements. However, it is unclear motifs are prone to impact transcriptional regulation if mutated. Current motif analysis tools either prioritize TFs based on enrichment without linking function or limited their applications due assumption linearity between and functional effects. Results We present MAGGIE (Motif Alteration Genome-wide Globally Investigate Elements), novel method for identifying mediating function. By leveraging measurements from diverse genotypes, uses statistical approach link mutations changes an epigenomic feature assuming linear relationship. benchmark across various using both simulated biological datasets demonstrate its improvement sensitivity specificity compared with state-of-the-art approaches. use gain insights into divergent functions distinct NF-κB factors pro-inflammatory macrophages, revealing association p65–p50 co-binding activation p50 lacking p65 repression. Availability implementation The Python package freely available at https://github.com/zeyang-shen/maggie. accession number ChIP-seq data generated this study Gene Expression Omnibus: GSE144070. Supplementary information Bioinformatics online.