: The study of the relationship between type 2 diabetes mellitus (T2DM) disease and other pathologies (comorbidities), together with patient age variation, poses a challenge for medical research. There is evidence that patients affected by T2DM are more likely to develop comorbidities as they grow older. Variation of gene expression can be correlated to changes in T2DM comorbidities insurgence and progression. Understanding gene expression changes requires the analysis of large heterogeneous data at different scales as well as the integration of different data sources into network medicine models. Hence, we designed a framework to shed light on uncertainties related to age effects and comorbidity by integrating existing data sources with novel algorithms. The framework is based on integrating and analysing existing data sources under the hypothesis that changes in the basal expression of genes may be responsible for the higher prevalence of comorbidities in older patients. Using the proposed framework, we selected genes related to comorbidities from existing databases, and then analysed their expression with age at the tissues level. We found a set of genes that changes significantly in certain specific tissues over time. We also reconstructed the associated protein interaction networks and the related pathways for each tissue. Using this mechanistic framework, we detected interesting pathways related to T2DM whose genes change their expression with age. We also found many pathways related to insulin regulation and brain activities, which can be used to develop specific therapies. To the best of our knowledge, this is the first study that analyses such genes at the tissue level together with age variations.
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