Network Biology for Rare Disease
Project acronym: RADINET
Topics: rare deseases, genes and proteins interactions, graph theory, networks biology
Disciplinary fields: mathematics, computer sciences, automatic, genetics, rare diseases, developmental biology
Summary: Rare monogenic diseases display a largely unexplained heterogeneity, many patients remain undiagnosed, and almost no treatment exists. The primary goal of RADINET is to untangle the genotype-phenotype complexity of rare diseases with systems and networks biology approaches. Disease complexities are the consequence of the intricate functioning of genes and proteins in cells, and–omics datasets, such as interactomes, transcriptomes or proteomes, offer an unprecedented opportunity to study the cellular functioning and its pathological deregulations. There is however a huge bottleneck around treatment, integration and interpretation of these data. The RADINET project will tackle this challenge by developing an innovative network-based approaches with solid bases in graph theory, and able to manage size, noise and complexity of large-scale biomedical data. A multiplex and heterogeneous network framework will gather thousands of physical and functional interactions between macromolecules. Advanced community identification algorithm and spacial probabilistic models will associate each disease to its profile of perturbed cellular processes and impacted tissues, thereby providing concrete hypotheses regarding disease etiologies and pathophysiologies. The comparison of the cellular process profiles of the different diseases will allow challenging their blurred nosologies and comorbidities. Finally, advanced random walk algorithms will explore and rank disease-pertinent sub-networks, toward innovative network-based diagnosis tools and drug repurposing strategies. RADINET will first be developed to study diseases associated to a premature aging phenotype, such as progeria, and then extended to other diseases, including muscular dystrophies and periphand peripheral neuropathies. It is to note that systems and networks biology, which aim to untangle disease complexity, remains to be applied to the field of rare diseases.
Project duration: 02/15/2018 – 03/14/2021
Call for application: Interdisciplinarité 2016