Hotel Estoril Eden, Monte Estoril,
Portugal
5-8 October 2005

 

 
 

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B
ayesian Network Analysis of Chromosomal Aberrations involving DNA Damage Response Network Genes

Nadjet S. El-Mehidi and Sylvia Nagl
Department of Oncology, Royal Free & University College Medical School, UK

Bayesian networks (BNs) are graphical representations of joint probability distribution over a domain of variables. BNs have been successfully used for genetic regulatory pathway and protein signalling network discovery. In addition to their interpretability by the human mind, their success depends largely on their probabilistic nature that can accommodate noise inherent in biologically derived data. Additionally BNs are robust to the existence of unobserved variables by describing both direct and indirect influences.

A complex network of cellular pathways, known as the DNA damage response network, regulates the integrity of the genome. The DNA damage response involves sensing of DNA damage followed by transduction of the damage signal to a network of cellular pathways including cell cycle checkpoints, DNA repair, telomere maintenance, and programmed cell death (apoptosis). Genomic instability leading to extensive gene copy number changes and inactivation of the apoptotic machinery is a common characteristic of cancer cells that have acquired resistance to radio- and chemotherapy.

The work presented in this poster demonstrates how Bayesian Networks can be used to study dependencies between chromosomal aberrations, involving DNA damage response genes, in different cancer types and how the insights gained from this analysis can facilitate analysis of abnormal karyotypes and their impact on the DNA damage response network and treatment response.