Knowledge Discovery and System Biology in Molecular Medicine: An Application on Neurodegenerative Diseases

Issue title: DAGSTUHL SEMINAR "INTEGRATIVE BIOINFORMATICS"

Article type: Research Article

Authors: Fattore, Matteo | Arrigo, Patrizio

Affiliations: CNR ISMAC, Section of Genoa, Via De Marini 6, 16149 Genova, Italy

Note: [] Corresponding author. Tel.: +39 010 6475882; E-mail: [email protected]

Abstract: The possibility to study an organism in terms of system theory has been proposed in the past, but only the advancement of molecular biology techniques allow us to investigate the dynamical properties of a biological system in a more quantitative and rational way than before. These new techniques can gave only the basic level view of an organisms functionality. The comprehension of its dynamical behaviour depends on the possibility to perform a multiple level analysis. Functional genomics has stimulated the interest in the investigation the dynamical behaviour of an organism as a whole. These activities are commonly known as System Biology, and its interests ranges from molecules to organs. One of the more promising applications is the 'disease modeling'. The use of experimental models is a common procedure in pharmacological and clinical researches; today this approach is supported by 'in silico' predictive methods. This investigation can be improved by a combination of experimental and computational tools. The Machine Learning (ML) tools are able to process different heterogeneous data sources, taking into account this peculiarity, they could be fruitfully applied to support a multilevel data processing (molecular, cellular and morphological) that is the prerequisite for the formal model design; these techniques can allow us to extract the knowledge for mathematical model development. The aim of our work is the development and implementation of a system that combines ML and dynamical models simulations. The program is addressed to the virtual analysis of the pathways involved in neurodegenerative diseases. These pathologies are multifactorial diseases and the relevance of the different factors has not yet been well elucidated. This is a very complex task; in order to test the integrative approach our program has been limited to the analysis of the effects of a specific protein, the Cyclin Dependent Kinase 5 (CDK5) which relies on the induction of neuronal apoptosis. The system has a modular structure centred on a textual knowledge discovery approach. The text mining is the only way to enhance the capability to extract ,from multiple data sources, the information required for the dynamical simulator. The user may access the publically available modules through the following site: http://biocomp.ge.ismac.cnr.it.

Keywords: System Biology, Knowledge Discovery, integrative bioinformatics, molecular medicine, Alzheimer's diseases, CDK5, virtual screening, drug design

Journal: In Silico Biology, vol. 5, no. 2, pp. 199-208, 2005