Dottorato in TECNOLOGIE BIOMEDICHE INNOVATIVE IN MEDICINA CLINICA

Titolo della tesi: An intelligent management of integrated biomedical data for digital health via Network Medicine and its application to different human diseases

Personalized medicine aims to tailor the health care to each person’s unique signature leading to better distinguish an individual patient from the others with similar clinical manifestation. Many different biomedical data types contribute to define this patient’s unique signature, such as omics data produced trough next generation sequencing technologies. The integration of single-omics data, in a sequential or simultaneous manner, could help to understand the interplay of the different molecules thus helping to bridge the gap between genotype and phenotype. To this end, Network Medicine offers a promising formalism for multi-omics data integration by providing a holistic approach that look at the whole system at once rather than focusing on the single entities. This thesis regards the integration of various omics data following two different procedures within the framework of Network Medicine: A procedural multi-omics data integration, where a single omics was first selected to perform the main analysis, and then the other omics were used in cascade to molecularly characterize the results obtained in the main analysis. A parallel multi-omics data integration, where the result was given by the intersection of the results of each single-omics. The procedural multi-omics data integration was leveraged to study Colorectal and Breast Cancer. In the Colorectal Cancer case study, we defined the molecular signatures of a new subgroup of Colorectal Cancer possibly eligible for immune-checkpoint inhibitors therapy. Moreover, in the Breast Cancer case study we defined 11 prognostic biomarkers specific for the Basal-like subtype of Breast Cancer. Instead, the parallel multi-omics data integration was exploited to study COVID-19 and Chronic Obstructive Pulmonary Disease. In the COVID-19 case study, we defined a pool of drugs potentially repurposable for COVID-19. Whereas, in the Chronic Obstructive Pulmonary Disease case study, we discovered a group of differentially expressed and methylated genes that have a considerable biological specificity and could be related to the inflammatory pathological mechanism of Chronic Obstructive Pulmonary Disease.