Deciphering intra- and inter-individual variation at single cell resolution

While the number of genetic variants associated with disease continues to increase, their function remains largely unknown. Thus, this project aims to generate the experimental and computational infrastructure to systematically interpret the function of these variants in complex human tissues both within (intra-individual variation) and across many individuals (inter-individual variation), applying single cell and spatial genomics to anatomically well-mapped samples. For this, researchers will generate a cellular molecular reference map from 29 banked tissues (from the GTEx/ENCODE collection) applying snRNA-Seq, scATAC-Seq and spatial analysis. To be followed by the assessment of the effect of genetic variation on gene regulation for atherosclerotic vascular disease. 

This way, researchers will leverage current, and develop new computational methods to associate variants with cell types, cell proportions, modules of co-regulated genes, mean and variance of gene expression as well as spatial features. The generated data will be integrated within a wealth of existing genomic and epigenomic datasets from GTEx and ENCODE. All generated data will be open access to facilitate the generation of a systematic blueprint for the functional interpretation of human disease-associated genetic variation, which will likely become a core resource for the Human Cell Atlas and propel our understanding of human biology, genetics and disease.