Diabetes has emerged as a global pandemic affecting more than 420 million people worldwide, a number expected to further rise in the next decades. The disease has very heterogeneous outcomes and accurate patient staging or prediction of subsets of individuals likely to develop disease and/or progress to disease complications are currently unmet clinical challenges in need of urgent attention. OPTOMICS aims to research methodology that can deliver a paradigm shift in type 2 diabetes healthcare, by integrating 1) molecular phenotyping, 2) a new generation of phenotypic measurements in humans, representative of diabetes onset and progression, allowed by novel portable and non-invasive optoacoustic technology and 3) cutting-edge computational approaches leveraging progress in Artificial Intelligence. This research will develop and validate a digital twin model that catalyses a step change in shortening the path to translation, enabling applications in the entire spectrum from target identification & prevention/prognosis to patient stratification for type 2 diabetes and its complications. In addition to the research and technology goals, OPTOMICS places special attention to the ethical needs and implications of the work performed and further aims at exemplary project management, human measurements, dissemination and communication activities and updating an adept exploitation plan for the digital twin developed.

The overall goal of this project is to bring the unique, ultra-fast Local Heating PCR technology and its current lab-proven prototype instruments from TRL 4 up to TRL 6 into clinical demonstration in tuberculosis centers in Italy, Latvia, and Tanzania. This will imply a fully automated workflow on the instrument and all necessary reagents onboard of the integrated disposable cartridge, and a cloud based software for tracking epidemiological patterns. The application, ultra-fast point-of-care testing (POCT) for tuberculosis (TB) as well as emerging TB resistance markers, is an unmet healthcare need, not only in Europe, but globally. About one third of the human population is thought to carry the pathogen. One patient with active TB can typically infect 10-15 others. In the EU, the highest incidence rates are observed in Eastern Europe and the Baltic region. Furthermore, a very recent surge has been observed in some EU countries, e.g. in Germany, mainly due to higher mobility and migration. On top of this, multi-drug resistant (MDR) TB strains are becoming epidemic, causing exploding treatment costs. Active tuberculosis needs to be rapidly detected at hospitals, in- and out-patient clinics, specialized TB centers, jails, community centers, and shelter facilities. Such a test should be highly sensitive and capture all of the clinically relevant mutations that confer resistance in TB; if only one mutation escapes detection, the wrong treatment decision might be made, leaving the patient infected and capable of spreading resistant pathogens. Therefore, a panel of multiplexed markers will be adopted to LPCR in this project. It is ultimately the project’s ambition to develop a European-based contender in the emerging molecular POCT system space. The integrated TB/MDR TB LPCR system, a break-through-technology, aims specifically at impacting healthcare, TB knowledge and capacity building, and enabling future commercial success of the products.

Chronic pain (CP) is the leading cause of disability, and is strongly associated with fatigue, anxiety and depression ─ also major contributors to disability, and with cardiovascular disease (CVD) and mortality. Twin studies indicate that these associations are a consequence of common causal mechanisms. The main objective of PainFACT is to identify these mechanisms. Using hypothesis-free genomic, proteomic, transcriptomic and brain-imaging discovery in available human studies and in a large cohort of outbred mice with multiple comorbidities, we aim to identify biomarkers that are associated across conditions. Predictive algorithms will be developed through machine learning techniques and tested in prospective analysis. Mendelian randomization approaches will be applied to test for causality. Mechanistic studies will be carried out in validated behavioral and atherosclerotic mouse models. Predictive markers will be tested as possible mediators of effects of lifestyle and obesity. Unique features of this program of research is the strong emphasis on experimental pain models and brain imaging techniques, facilitating translation of findings between mice and humans, and exploitation of the largest study of experimental pain worldwide and of multiple clinical datasets ranging in size from tens of thousands to 1.1 million. A custom protein panel will be developed together with sex and age stratified algorithms, with expected impact for the prediction and monitoring of disease and comorbidity, and for tracking effects of life-style changes. It is also expected that PainFACT results will have major impact on the diagnostic criteria and classification of affective disorders and CP. The identification of novel causal biomarkers will provide new targets for development of medicines and yield new insight into the causes of comorbidity.