Center for Spatial and Functional Genomics

Intense genome wide efforts by the research community have yielded key variants robustly associated with both rare monogenic disorders and common complex traits across the lifecycle. However, an important caveat of uncovering non-coding variants associated with a trait is that the precise location of the actual underlying culprit gene(s) is not immediately obvious.

The Center for Spatial and Functional Genomics at the Children’s Hospital of Philadelphia conducts such 'variant-to-gene mapping' efforts. Our team is determining, at scale, how disease-associated non-coding variants affect the expression of specific genes in relevant cell types. This involves the integration of high-resolution 3D Genomics, assay for transposase accessible chromatin sequencing (ATAC-seq), RNA-seq, CRISPR and bioinformatics.

The premise of our collaborative research is to uncover the correct functional context of non-coding variants contributing to disease susceptibility in order to translate these discoveries into meaningful benefits for pediatric care. This approach in the relevant human cellular models is particularly timely given the relative paucity of public domain genomic data relevant to many key cell types.