Technical Approach
The PrECISE project is planned to run for 36 months. It is organized into nine work packages with significant dependencies and expected synergies between them which are described shortly in the following.
WP1: Regulatory network and clonality inference in prostate cancer tumours
WP1 provides the basis for clone identification and associated biomarkers. Therefore, regulatory networks and clonality analyses of proCOC tumour biopsies as well as public prostate genomic profiles are used.
WP2: Identification of sub-clonal genomic alterations
This WP identifies sub-clonal genomic alterations and describes intra-tumour heterogeneity in prostate cancer through protein profiling and ultra-deep sequencing in the proCOC samples and additional selected CRPC biopsies.
WP3: Reconstruction of protein interaction networks from high-dimensional proteomic maps and IBM – Watson technology
WP3 provides data-driven context-specific interaction networks out of the SWATH mass spectrometry for the proCOC samples, prostatic cell lines and public proteomic data. Another focus will be on network reconstruction algorithms that incorporate automatic text-mining capabilities through the Watson cognitive computer.
WP4: Linking genetic variation to protein expression
WP4 aims at incorporating genomic, transcriptomic and proteomic maps into a comprehensive molecular map, which is then utilized to detect clusters of proteins enriched in genomic alterations. It shall also identify key pathways and molecular mechanisms that underlie cancer progression specific clones and it shall help to develop a multidata patient classifier to group patients in clinically meaningful groups.
WP5: Logic models of prostate cancer patients: predicting personalized drug therapies
The objective of WP5 is to develop a mathematical model that includes the key molecular players identified in upstream WPs and that can provide a qualitative understanding of cancer underlying molecular mechanisms.
WP6: Experimental validation of prognostic biomarkers and targeted drug predictions
WP6 is a validation WP that creates quantitative proteomic and genomic datasets from selected samples. These new data will be used to validate inferred biomarkers and dysregulated pathways.
WP7: Graphical user interface
This WP provides an interface for analyses and prognostic inference from molecular profiles. A dashboard is established that contains all project data in order to select, control, execute or display the analyses.
WP8: Dissemination, Communication, Exploitation and Training
WP8 focuses on communication and dissemination of scientific research results achieved within the individual WPs to outside parties as well as to participating entities. Furthermore, this WP will support the partners to exploit the achieved results and impact the European as well as the international market. Moreover, WP8 results will lead to contributions in terms of trainings.
WP9: Project, Risk and Innovation Management
Finally, WP9 ensures a successful project lifetime with respect to risk and innovation management. There are dependencies to all other work packages as this WP coordinates the tasks so that they are in line with the project work plan in order to reach the objectives of PrECISE.