3TR is a transdisciplinary consortium made of experts in all areas of medicine, basic sciences and bioinformatics from academic institutions, SMEs, and 8 major pharmaceutical companies, teamed to study a fundamental issue in medicine: the mechanisms of response and non-response to therapies, the major aim of 3TR, both within single disease entities and across diseases, where molecular stratification may identify shared disease taxonomies. The molecular identification of groups of patients to whom a drug will benefit, will allow focusing on those who are drug orphan. Harmonization of data from existing academy or industry-sponsored studies will identify biomarkers to inform a new collection. Specimens of diseased tissues, blood, stools, and other fluids will be obtained in a de novo observational prospective trial with standard of care medication prior, during and after first or second line of treatment. Because the studies will be at different phases of progression, a carrousel model of work was designed for input and output of data to be continuously analysed, and interpreted, to inform those measurements to be undertaken and allow cross-validation of results. The 3TR team will elucidate the role of the microbiome, genetics and regulatory genomic features in disease progression. The working aims of 3TR are: 1) establish a centralized data management platform; 2) perform comprehensive molecular and clinical characterisation of a prospective patient cohort; 3) establish integrated analysis of all data using advanced bioinformatics/statistical and modelling methods; 4) identify sets of predictive biomarkers of response/non-response to therapies; 5) improve the competitiveness of European industry and support development of novel solutions. 3TR will sustain beyond the project end the samples and its knowledge base. 3TR will challenge and revolutionize the conventional single-disease based approach with important implications in future disease treatment.

Recent developments in omics technologies demand implementation of systems biology approaches to facilitate analysis and interpretation of the generated complex datasets.This is essential for biotechnological as well as preclinical and clinical applications. In comparison to previous approaches, most cancer relevant studies are confined to pattern recognition or at best modelling of single pathways, rather than the complex pathways and cross-talk determining cancer progression and drug response. Systematic tools that evaluate and validate personalised medicine approaches on a preclinical level are missing; an important prerequisite for translation into clinical practice. The overall objective of CanPathPro is to build and validate a new biotechnological application: a combined experimental and systems biology platform, which will be utilized in testing cancer signaling hypotheses in biomedical research and life sciences. Thus, the proposed project will focus on developing and refining bioinformatic and experimental tools for the evaluation of systems biology modelling predictions. Components comprise a highly controlled mouse experimental system, NGS, a quantitative proteomics based read-out of changes in pathway signalling and an integrative systems biology model for data integration. Testable hypotheses about biological systems will be generated and experimentally validated. The developed system tools will be made available to researchers, SMEs and industry for practical applications. Following this project, a commercial platform for interpretation and analysis of complex omics data and for deriving and testing new hypotheses will be set up by the participating companies and academic partners. CanPathPro will enhance the competitive potential of the SMEs involved expanding in the field of biotechnology, personalised medicine and drug development and also provide new opportunities for other SMEs working in the field of bioinformatics and biomedical applications.

SMARTool aims at developing a platform based on cloud technology, for the management of patients with coronary artery disease (CAD) by standardizing and integrating heterogeneous health data, including those from key enabling technologies. The platform includes existing multiscale and multilevel ARTreat (FP7-224297) models of coronary plaque progression based on non-invasive coronary CT angiography (CCTA) and fractional flow reserve computation, refined by heterogeneous patient-specific non-imaging data (history, lifestyle, exposome, biohumoral data, genotyping) and cellular/molecular markers derivable from a microfluidic device for on-chip blood analysis. SMARTool models will be applied and validated by historical and newly acquired CCTA imaging plus non-imaging health data from the EVINCI project (FP7-222915) population. SMARTool cloud-based platform, through Human Computer Interaction techniques, 3D visual representation and artery models, will use heterogeneous data in a standardized format as input, providing as output a CDSS - assisted by a microfluidic device as a point of care testing of inflammatory markers – for: i) Patient specific CAD stratification - existing models, based on clinical risk factors, will be implemented by patient genotyping and phenotyping to stratify patients with non-obstructive CAD, obstructive CAD and those without CAD, ii) site specific plaque progression prediction - existing multiscale and multilevel ARTreat tools of CAD progression prediction will be refined by genotyping and phenotyping parameters and tested by baseline and follow CCTA and integrated by non-imaging patient-specific data, iii) patient-specific CAD diagnosis and treatment - life style changes, standard or high intensity medical therapy and a virtual angioplasty tool to provide the optimal stent type(s) and site(s) for appropriate deployment.