Spatial & Functional
Genomics Affinity Group

Genome-Scale, Promoter-focused Analysis of chromaTIn Looping (SPATIaL-seq)

It is known that genome wide association study (GWAS) efforts only report genomic signals and not necessarily the precise localization of culprit genes. Given the need to improve upon the low resolution of typical Hi-C approaches, we have developed a massively parallel, high-resolution Capture-C based method to characterize the genome-wide interactions of all human promoters in various cell settings. We have designed a custom Agilent SureSelect RNA library targeting DpnII restriction fragments overlapping promoters of protein-coding, noncoding, antisense, snRNA, miRNA, snoRNA and lincRNA genes. We are now applying our method of SPATIaL-seq to multiple disease-relevant cell types. We also generate ATAC-seq open chromatin maps from the same samples to identify the most likely functional proxy SNPs for each GWAS locus for a given trait. By intersecting our sub-1kb SPATIaL-seq data with the ATAC-seq data, we observe consistent contacts between "open" promoters and proxy SNPs for various loci. Only by establishing which specific genes at such loci are regulated in the correct cellular context can one truly translate GWAS findings in to more efficacious treatments for common diseases.