Interdiscip Sci Comput Life Sci (2013) 5: 175–186 DOI: 10.1007/s12539-013-0172-y A Computational Model for Genetic and Epigenetic Signals in Colon Cancer Irina Afrodita ROZNOV ˇ AT ¸ ∗ , Heather J. RUSKIN (Centre for Scientific Computing & Complex Systems Modelling (SCI-SYM), School of Computing, Dublin City University, Dublin 9, Ireland) Received 7 January 2013 / Revised 30 March 2013 / Accepted 12 June 2013 Abstract: Cancer, a class of diseases, characterized by abnormal cell growth, has one of the highest overall death rates world-wide. Its development has been linked to aberrant genetic and epigenetic events, affecting the regula- tion of key genes that control cellular mechanisms. However, a major issue in cancer research is the lack of precise information on tumour pathways; therefore, the delineation of these and of the processes underlying disease pro- liferation is an important area of investigation. A computational approach to modelling malignant system events can help to improve understanding likely “triggers”, i.e. initiating abnormal micro-molecular signals that occur during cancer development. Here, we introduce a network-based model for genetic and epigenetic events observed at different stages of colon cancer, with a focus on the gene relationships and tumour pathways. Additionally, we describe a case study on tumour progression recorded for two gene networks on colon cancer, carcinoma in situ. Our results to date showed that tumour progression rate is higher for a small, closely-associated network of genes than for a larger, less-connected set; thus, disease development depends on assessment of network properties. The current work aims to provide improved insight on the way in which aberrant modifications characterize cancer initiation and progression. The framework dynamics are described in terms of interdependencies between three main layers: genetic and epigenetic events, gene relationships and cancer stage levels. Key words: genetic and epigenetic events, cancer, gene relationship, computational model. 1 Introduction Over the last two decades, it has become increas- ingly evident that not only genetic, but also epigenetic inheritance is important in many pathological condi- tions, and relates to features, such as loss of imprinting, hyper- and hypomethylation (Jelinic and Shaw, 2007), and chromatin remodelling, (Allis et al., 2007). Defined as heritable changes in chromatin structure which af- fect gene expression, but do not include modifications in DNA sequence (Allis et al., 2007), epigenetic sig- nals have been detected in the earliest stages of dif- ferent neoplastic diseases (Herman and Baylin, 2003), and acted as markers for cancer initiation. Addition- ally, their unique reversibility property (not shared by genetic mutations (Dworkin et al., 2009)), is already exploited in some therapy regimes (Egger et al., 2004; Karpf and Jones, 2002). Nowadays, treatments in incipient stages of cancer (i.e. localized, non-metastasized tumours) are more ef- fective (Egger et al., 2004; Karpf and Jones, 2002), and * Corresponding author. E-mail: iroznovat@computing.dcu.ie it is known that the early detection of abnormal cel- lular changes within the body can contribute to suc- cess in inhibiting tumour growth (Laird, 2003). Given time and cost implications of human genome exper- imentation, computational modelling is progressively being employed to improve understanding of mecha- nisms which determine malignant tumour growth. In this paper, we focus on genetic and epigenetic events that induce aberrant DNA methylation in cells and pro- pose a network-based model to describe their interde- pendencies in colon cancer development. 2 Background Cancer is caused by the deregulation of key genes that control cellular mechanisms, including mitosis, meiosis, apoptosis, and movement. Gene transcription is controlled by chromatin, which can change dynam- ically due to different epigenetic events, such as DNA methylation (DNAm) and histone modifications (HM) (Bock and Lengauer, 2008; Lim et al., 2010). DNA methylation is a molecular process that involves the addition of a methyl group to a cytosine ring. In can- cer development, aberrant DNA methylation patterns