PRECISE: Identification of biomarkers and therapeutic targets in inflammatory disease immunotherapy by high-dimensional single cell analysis and cluster proteomics. – PHRT
PRECISE: Identification of biomarkers and therapeutic targets in inflammatory disease immunotherapy by high-dimensional single cell analysis and cluster proteomics.
Recent advances in immunotherapy have provided a breakthrough in the treatment of patients suffering from chronic inflammatory disease. While the successes of immunotherapy are decisive, several inflammatory diseases remain untreatable. The identification of disease biomarkers and stratifiers of therapy responses is therefore a fundamental and urgent goal of personalized medicine.
Goals & Significance
This project aims at interoperability of the Swiss personalized health research infrastructure network by subjecting routinely acquired patient biopsies and clinical covariates across multiple centers to a central, standardized and integrated analysis workflow. This interoperability enabling pipeline will be made available for future studies by technology translation to dedicated facilities at ETHZ/UZH and by data exposition in the SPHN/SIB coordinated BioMedIT infrastructure. Our vision is to open this pipeline to all clinical centers nationally, as well as other disease classes and to implement routine procedures across Switzerland for sampling and bio banking.
PRECISE aims at identification of such biomarkers and stratifiers and proposes to acquire liquid and solid biopsies from patients suffering from chronic inflammatory disease, with a focus on those treated with immunotherapy. This material will be part of multiple independently ongoing clinical studies carried out in various Swiss clinical institutions, namely university hospitals in Zürich, Basel, Bern and Lausanne. High-dimensional single cell cytometry combined with computer-aided analysis will be used to identify cell type signatures, i.e. possibly rare, disease relevant cell subpopulations as reliable biomarkers and novel therapeutic targets. Further, identified signature cell types will be subjected to proteomic mass spectrometric analysis and epigenetic screening to provide an in depth view of the biochemical state of disease-relevant cell types. Upon validation in independent patient cohorts, this information will then be used to stratify patients prior to immunotherapy to maximize the therapeutic impact and to minimize adverse effects as well as to provide new personalized therapeutic targets for immune intervention across the Swiss wide patient population.
Kopf A, Fortuin V, Somnath VR, Claassen M. Mixture-of-Experts Variational Autoencoder for clustering and generating from similarity-based representations, PLoS Comput Biol 17(6): e1009086. https://doi.org/10.1371/journal.pcbi.1009086