Allele specific chromatin signals, 3D interactions, and motif predictions for immune and B cell related diseases

Scientific Reports
Marco CavalliClaes Wadelius

Abstract

Several Genome Wide Association Studies (GWAS) have reported variants associated to immune diseases. However, the identified variants are rarely the drivers of the associations and the molecular mechanisms behind the genetic contributions remain poorly understood. ChIP-seq data for TFs and histone modifications provide snapshots of protein-DNA interactions allowing the identification of heterozygous SNPs showing significant allele specific signals (AS-SNPs). AS-SNPs can change a TF binding site resulting in altered gene regulation and are primary candidates to explain associations observed in GWAS and expression studies. We identified 17,293 unique AS-SNPs across 7 lymphoblastoid cell lines. In this set of cell lines we interrogated 85% of common genetic variants in the population for potential regulatory effect and we identified 237 AS-SNPs associated to immune GWAS traits and 714 to gene expression in B cells. To elucidate possible regulatory mechanisms we integrated long-range 3D interactions data to identify putative target genes and motif predictions to identify TFs whose binding may be affected by AS-SNPs yielding a collection of 173 AS-SNPs associated to gene expression and 60 to B cell related traits. We present a syste...Continue Reading

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Citations

May 14, 2021·Nature Communications·Sergey AbramovIvan V Kulakovskiy
Apr 9, 2021·Bioinformatics·Julia MarkowskiRoland F Schwarz
Jul 3, 2021·International Journal of Molecular Sciences·Arina O DegtyarevaTatiana I Merkulova
Sep 2, 2021·Annual Review of Biomedical Data Science·Siobhan Cleary, Cathal Seoighe

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Datasets Mentioned

BETA
GM12878
2221835
GM18505
2976970
GM18526
GM18951
2092387
GM19099
2978401
1904

Methods Mentioned

BETA
RNA-seq
ChIP-seq
HiC
the

Software Mentioned

AlleleSeq
Bioconductor
ALEA toolbox
- C User Pipeline )
HiCap
iASeq
Perl
ALEA
HiCapTools
InMoDe

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