I'm interested in understanding and predicting the relationships between the sequences, structures and functions of proteins, the evolutionary conservation of these features and their alterations upon mutations leading to diseases. To that aim, I develop original methodologies for sequence analysis, especially based on the HCA approach (see below). Together with other tools, these help revealing information into yet unexplored areas of computational biology. These are applied to the evolutionary analysis of protein domains and protein architectures, with a special interest in the analysis of orphan protein domains and in the discovery of new families of domains, which are not yet described. Topology-based methodologies are also developed to address fundamental issues about protein folding and protein interaction properties.