Roznovăţ Irina A, Ruskin Heather J
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.
Centre for Scientific Computing & Complex Systems Modelling (SCI-SYM), School of Computing, Dublin City University, Dublin, Ireland.
IET Syst Biol. 2015 Dec;9(6):259-67. doi: 10.1049/iet-syb.2015.0048.
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.
表观遗传学正成为生物学和医学研究中一个极其重要的领域，这对于我们理解包括癌症、自身免疫性疾病和神经精神疾病在内的人类疾病具有重要意义。在近期个性化医疗的研究背景下，一个新的研究方向关注与疾病易感性和发展相关的个体内表观遗传变异的识别，即全表观基因组关联研究。已经开发了一个计算模型来描述人类肠道隐窝的动态和结构，并对癌症起始过程中这些隐窝中诱导产生的异常DNA甲基化水平进行比较分析。隐窝框架AgentCrypt是一种基于主体的隐窝动力学模型，它处理内部和相互依赖性。此外，AgentCrypt模型用于研究一组潜在抑制剂对疾病起始过程中肠道组织甲基化修饰的影响。与小肠相比，结肠在相对较短的90天内甲基化水平下降明显，尽管两种组织中都诱导了类似的变化。此外，抑制剂对异常隐窝组的影响显著，存在抑制剂时，结肠中观察到的平均甲基化差异最大降低约0.75%，小肠中降低约0.79%。
