An integrated bioinformatics digital ecosystem platform for a rare disease to address –omics challenges in Precision Medicine

Precision Medicine (PM) is an emerging approach that integrates research disciplines and clinical practice to build a knowledge base network that can better guide individualized patient care. Undoubtedly, PM application to common and rare diseases will give benefit to patients and families/carers in terms of health and life quality. Alkaptonuria (AKU) is a severely invalidating ultra-rare inborn error of metabolism with no apparent genotype-phenotype relationship, no prognosis and no therapy. To facilitate the application of PM approach to AKU, we have developed ApreciseKUre, an integrated interactive digital platform (www.bio.unisi.it/aprecisekure/; www.bio.unisi.it/aku-db/) populated with data derived from more than 200 AKU patients. The collection, integration and analysis of clinical and experimental data streams are shared between researchers, clinicians and patients in order to develop an AKU-dedicated Precision Medicine Ecosystem (PME). Data are stratified into different layers related to genotype, biomarkers, environment, lifestyle, habit, histopathologic, social functioning, clinical and therapies of patients. ApreciseKUre is not only a data storage but it is also integrated with different analytic techniques that make it a good computational model for: - the creation of a new clinical management tool for patients stratification, - the development of a deeper knowledge network on the disease and advancement of its treatment, - becoming aware of the failure of biomarkers clinically used, - improving the detection of more exploitable prognostic biomarkers for AKU clinical monitoring. The growth of ApreciseKUre during these years allowed to build data-driven models able to map highly non-linear input and output and to investigate the health status of an AKU patient patterns even when mechanistic relationships between model variables could not be determined. The project aims to shift from disease to wellness, with enormous expected cost savings to society resulting in a lower requirement for sick leave and a concurrent increase in health-care.