Single-Cell Genomics Core technology platform for biomedical research and clinical applications – PHRT
Single-Cell Genomics Core technology platform for biomedical research and clinical applications
Single-cell genomic profiling can report the precise combination of genetic variations, gene expression states and chromatin signatures in any given cell providing the highest possible resolution for resolving cell-to-cell variation. With the Single-Cell Genomics Core technology platform, we will evaluate and establish robust experimental and computational solutions that can be directly applied to biomedical research and clinical applications.
This project aims at establishing a translational technology platform dedicated to the development and implementation of single-cell genomic profiling workflows for biomedical research and clinical applications. The Single-Cell Genomics Core platform will serve as hub of expertise for evaluating and establishing single-cell genomics applications. In the course of this proposal, the infrastructure for state-of-the-art single-cell genomic profiling is established which involves not only the experimental but also the subsequent computational analysis workflows. In pilot studies with clinical partners from SPHN projects and beyond the benefit of applying single-cell profiling will be evaluated to finally come up with robust workflows starting from dissected tissue material via data generation and analysis back to inform clinical decision making.
The emerging field of single-cell genomics is advancing rapidly and is generating many new insights into complex biological systems, like the human brain, immune system and tumors. Genomic profiling in single cells will have a big impact on clinical applications in the coming years. For example, resected tumors might be routinely assessed for the presence of rare malignant and chemo-resistant cancer cells. Such data will provide crucial diagnostic information and will guide decisions regarding treatment. Tissue biopsies containing only a small number of cells, for example from gut mucosal surfaces, can be interrogated by single-cell profiling technologies providing molecular data that informs on diagnosis, disease progression, and appropriate treatment. Furthermore, immune-repertoire profiling will provide detailed information on the response of immune cells, which will inform diagnoses and the choice of therapy. In order to partake in this promising field a strong technology platform is required to support biomedical and clinical researchers in setting up robust experimental and analytical pipelines for data generation and interpretation.
Bulk genomic sequencing provides detailed knowledge of the relative frequencies of aberrations in a sample via well-developed bioinformatics pipelines. By contrast, single-cell genomics measurements can report the precise combination of gene variants, expression profiles or epigenetic marks in any given cell providing the highest possible resolution for resolving clonal subpopulations. The ability to interrogate single-cell states offers invaluable insight into critical molecular processes important to both health and disease. Although single-cell genomics studies have been conducted mostly by expert research groups over the past years, it has become evident that biomedical researchers and clinicians can make important new discoveries using powerful NGS-based single-cell profiling approaches. There is a strong need coming from Personalized Health related projects to keep up with the rapidly evolving field of single-cell genomics.
Dr. Christian Beisel
Department of Biosystems Science and Engineering, ETH Zurich