Projects

In principle, a multifaceted omics profile can be constructed for single cells by using separate single-cell profiling strategies. However, conducting the necessary measurements with high sensitivity, specificity and without drop-outs is still a challenge. The ultrahigh sensitivity of the “Emulsion Coupling (EC)” technology for measuring protein-protein-interactions has already been proven by detection of a new kind of influenza virus receptor (Nature; doi:10.1007/s12253-016-0094-1). The high sensitivity, inherent parallelism and also the simplicity due to the homogenous design (mix & read) make EC-assays an ideal tool for multifaceted single-cell analysis. The MONOGRAM project proposes a new assay paradigm combining the robust, digital, high dynamic range EC assay technology, single-cell printing (SCP), next-generation sequencing (NGS) and innovative bioinformatic tools towards a digital single-cell multi-omics analysis. To assay acute myeloid leukemia (AML) patients' samples single cells will be isolated using SCP technology, simultaneous DNA, RNA and protein and protein-protein-interaction detections are carried out using EC, and the assay is read by NGS and analysed by novel bioinformatics. The combined EC, SCP, NGS technologies could have transformative potential in the field of personalized single-cell based diagnostics. This potential will be demonstrated by setting up a single-cell phenotyping method for AML designed to answer the emerging non-genetic, adaptive resistance in AML patients treated with hypomethylating agents.