PQG Seminar

Oliver Stegle

Professor of Computational Genomics and Systems Genetics
EMBL Heidelberg

From genotype to phenotype with single-cell resolution

The study of genetic effects on gene expression using bulk-RNA sequencing has enabled the identification of quantitative trait loci (eQTL), which link inherited genetic variants to gene expression changes across different human tissues. Advances in single-cell RNA sequencing (scRNA-seq) provide for unprecedented opportunities to greatly increase the resolution of eQTL mapping approaches, thereby assaying gene regulatory effects at the resolution of cell types, cell states and even within individual cells in human tissues. In this talk, we will present novel experimental strategies combined with computational methods to enable population-scale single-cells sequencing. I will describe applications to single-cell profiling of human induced pluripotent stem cells across cellular differentiation. These data allow for identifying regulatory variants in a continuous manner across cellular transitions. Finally, we will describe analytics strategies for estimating genetic effects in single-cells, which allows for fine-mapping the most relevant cell types and cell states of human disease loci.