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Series GSE144070 Query DataSets for GSE144070
Status Public on Jul 17, 2020
Title Leveraging genetic variation to identify divergent functions of distinct NF-kB factors on the activity of regulatory elements in macrophages
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Genetic variation in regulatory elements can alter transcription factor (TF) binding by mutating a TF binding motif, which in turn may affect the activity of the regulatory elements. However, it is unclear which motifs are prone to impact transcriptional regulation if mutated. Current motif analysis tools either prioritize TFs based on motif enrichment without linking to a function or are limited in their applications due to the assumption of linearity between motifs and their functional effects. We present MAGGIE, a novel method for identifying motifs mediating TF binding and function. By leveraging measurements from diverse genotypes, MAGGIE uses a statistical approach to link mutations of a motif to changes of an epigenomic feature without assuming a linear relationship. We benchmark MAGGIE across various applications using both simulated and biological datasets and demonstrate its improvement in sensitivity and specificity compared to the state-of-the-art motif analysis approaches. We use MAGGIE to gain novel insights into the divergent functions of distinct NF-κB factors in pro-inflammatory macrophages, revealing the association of p65-p50 co-binding with transcriptional activation and the association of p50 binding lacking p65 with repression. The Python package for MAGGIE is freely available at
Overall design p65 and p50 ChIP-seq for BMDMs (bone marow-derived macrophages) from C57BL/6J mice stimulated with KLA for 1 hour.
Contributor(s) Hoeksema MA, Shen Z, Glass CK
Citation(s) 32657363
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 DK091183 Transcriptional co-regulators and macrophage gene expression THE REGENTS OF THE UNIV. OF CALIF., UNIV. OF CALIF., SAN DIEGO Christopher K Glass
Submission date Jan 22, 2020
Last update date Jul 20, 2020
Contact name Christopher K Glass
Phone 858-534-6011
Organization name University of California, San Diego
Department CMM
Lab Glass Lab
Street address 9500 Gilman Drive
City La Jolla
State/province CA
ZIP/Postal code 92093
Country USA
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (3)
GSM4279136 ChIP_p65_BMDM_KLA
GSM4279137 ChIP_p50_BMDM_KLA
GSM4279138 ChIP_input_BMDM_KLA
BioProject PRJNA602691
SRA SRP243915

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE144070_ChIP_p65_p50_merged_BMDM_KLA.peak.tag.txt.gz 2.5 Mb (ftp)(http) TXT
GSE144070_RAW.tar 1020.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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