Building Efficient NCDs (NonCommunicable Diseases) Early Warning Tools (BE NEWT)

We are applying for a major SSF project entitled Building Efficient NCDs (Noncommunicable Diseases) Early Warning Tools (BE NEWT) in the field of Medicine 3; 3.01 Microbiology and Immunology. The lead applicant of the project is the Chemical Institute in collaboration with four partners: the Jožef Stefan Institute, the University Clinical Centre Ljubljana, the Faculty of Electrical Engineering of the University of Ljubljana and ELIXIR-SI. NCDs are a major cause of ill health worldwide and their burden is increasing due to ageing and changing population demographic patterns. The burden of NCDs is particularly high in the WHO European Region. The EU4Health 2021-2027 programme responds to the long-term health challenge with the objectives of (i) promoting health and preventing disease and (ii) strengthening health data, digital tools and services and the digital transformation of healthcare. Since December 2021, Together Healthier - EU for Non-Communicable Diseases (NCDs) 2022-2027 (cardiovascular diseases, diabetes, chronic respiratory diseases, mental health and neurological disorders, cancer), and the European Cancer Plan, steer coordinated efforts to prevention, care, better knowledge, data, screening and early detection, diagnosis. Microbiomes contribute to thousands of metabolites in the blood through their metabolic activities. The majority of metabolites and interactions in blood and faeces are exclusively microbiome-derived (>65% and >70%, respectively), and act as modifiers of signalling, energy and other pathways and molecules, and hence influence human health. This project aims to: (i) Develop the (Gut) Microbiome Response Chip (GMRC) as a new tool for intensive real-time monitoring of personalised metabolic reactions of the gut microbiome. (ii) Mapping the gut microbiome space in conjunction with the associated urine metabolomes using the most powerful analytics (chemical, genomic), to produce big data amenable for ML/AI, to integrate multiple data layers, from stool and urine (including serum and swabs) for the same subjects, allowing us to build an infrastructure to integrate data from both data streams (gut-urine) for in-depth exploration and database growth. (iii) Apply the developed tools on real clinical stool and urine samples to design NCDs early warning tools considering as input GMRC data, gut microbiome metagenomic, metabolomic and chemical data, next to associated urine chemical and metabolomic space, to build classification models for unknown samples as tools,and search for biomarkers. SWOT assessment of analytical techniques will be used to design a more limited set of the most cost-effective measurements and methods. (iv) Ethical and legal aspects of the work, medical ethics approvals, establishment of effective data protection measures and procedures up to and beyond project completion will be conducted in line with advanced supra/national (EGA; https://ega-archive.org/), Data Access Committees (https://ega-archive. org/dacs). (v) Secure integration of medical data, developed protocols, pipelines and databases with structured, working, accessible and secure databases on the ELIXIR-SI portal to create the infrastructure of the future and integrate new datasets to enable further growth of databases towards existing SVIT programmes (https://www. program-svit.si/en/), DORA (https://dora.onko-i.si/english, ZORA (https://zora.onko-i.si/en). (vi) Manage, publish and use the project to realise the main grand objective of the project, which is to develop a screening approach as an early warning tool for NCDs in support of digitisation, innovation in the use of real-world data to open new avenues for the control of NCDs in line with EU health programmes and initiatives, and to enable systematic studies of interactions between drugs/chemicals and the microbiome and human health, both at an individual as well as at an integral population scale.