title: Theoretical cross-comparative analysis on dynamics of small intestine and colon crypts during cancer initiation.
abstract: Epigenetics is emerging as a fundamentally important area of biological and medical research that has implications for our understanding of human diseases including cancer, autoimmune and neuropsychiatric disorders. In the context of recent efforts on personalised medicine, a novel research direction is concerned with identification of intra-individual epigenetic variation linked to disease predisposition and development, i.e. epigenome-wide association studies. A computational model has been developed to describe the dynamics and structure of human intestinal crypts and to perform a comparative analysis on aberrant DNA methylation level induced in these during cancer initiation. The crypt framework, AgentCrypt, is an agent-based model of crypt dynamics, which handles intra- and inter-dependencies. In addition, the AgentCrypt model is used to investigate the effect of a set of potential inhibitors with respect to methylation modification in intestinal tissue during initiation of disease. Methylation level decrease over a relatively short period of 90 days is marked for the colon compared to the small intestine, although similar alterations are induced in both tissues. In addition, inhibitor effect is notable for abnormal crypt groups, with largest average methylation differences observed ≈0.75% lower in the colon and ≈0.79% lower in the small intestine with inhibitor present.
authors.affiliation: Current address: European Institute for Systems Biology and Medicine (EISBM), CNRS-ENS-UCBL, Campus Charles Mérieux, Université de Lyon, 50 Avenue Tony Garnier, 69366 Lyon cedex 07, France. iroznovat@eisbm.org.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Roznovăţ
authors.affiliation: Centre for Scientific Computing & Complex Systems Modelling (SCI-SYM), School of Computing, Dublin City University, Dublin, Ireland.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ruskin
mesh_terms: D058739:Aberrant Crypt Foci / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological
chemical_list: D004273:DNA, Neoplasm