Kumar Gaurav, Breen Edmond J, Ranganathan Shoba
ARC Centre of Excellence in Bioinformatics and Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.
BMC Syst Biol. 2013 Feb 6;7:12. doi: 10.1186/1752-0509-7-12.
Cancer is a complex disease where molecular mechanism remains elusive. A systems approach is needed to integrate diverse biological information for the prognosis and therapy risk assessment using mechanistic approach to understand gene interactions in pathways and networks and functional attributes to unravel the biological behaviour of tumors.
We weighted the functional attributes based on various functional properties observed between cancerous and non-cancerous genes reported from literature. This weighing schema was then encoded in a Boolean logic framework to rank differentially expressed genes. We have identified 17 genes to be differentially expressed from a total of 11,173 genes, where ten genes are reported to be down-regulated via epigenetic inactivation and seven genes are up-regulated. Here, we report that the overexpressed genes IRAK1, CHEK1 and BUB1 may play an important role in ovarian cancer. We also show that these 17 genes can be used to form an ovarian cancer signature, to distinguish normal from ovarian cancer subjects and that the set of three genes, CHEK1, AR, and LYN, can be used to classify good and poor prognostic tumors.
We provided a workflow using a Boolean logic schema for the identification of differentially expressed genes by integrating diverse biological information. This integrated approach resulted in the identification of genes as potential biomarkers in ovarian cancer.
癌症是一种复杂疾病,其分子机制仍不清楚。需要一种系统方法来整合各种生物信息,以便使用机械方法进行预后和治疗风险评估,从而理解通路和网络中的基因相互作用以及功能属性,以揭示肿瘤的生物学行为。
我们根据文献报道的癌基因和非癌基因之间观察到的各种功能特性对功能属性进行加权。然后,这种加权模式被编码到一个布尔逻辑框架中,以对差异表达基因进行排名。我们从总共11173个基因中鉴定出17个差异表达基因,其中10个基因据报道通过表观遗传失活而下调,7个基因上调。在此,我们报告过表达基因IRAK1、CHEK1和BUB1可能在卵巢癌中起重要作用。我们还表明,这17个基因可用于形成卵巢癌特征,以区分正常人和卵巢癌患者,并且CHEK1、AR和LYN这三个基因可用于对预后良好和不良的肿瘤进行分类。
我们提供了一种使用布尔逻辑模式的工作流程,通过整合各种生物信息来鉴定差异表达基因。这种综合方法导致鉴定出基因作为卵巢癌的潜在生物标志物。