College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Hei Longjiang Province, China.
PLoS One. 2011;6(9):e24495. doi: 10.1371/journal.pone.0024495. Epub 2011 Sep 6.
Disease genes that interact cooperatively play crucial roles in the process of complex diseases, yet how to analyze and represent their associations is still an open problem. Traditional methods have failed to represent direct biological evidences that disease genes associate with each other in the pathogenesis of complex diseases. Molecular networks, assumed as 'a form of biological systems', consist of a set of interacting biological modules (functional modules or pathways) and this notion could provide a promising insight into deciphering this topic.
METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we hypothesized that disease genes might associate by virtue of the associations between biological modules in molecular networks. Then we introduced a novel disease gene interaction pathway representation and analysis paradigm, and managed to identify the disease gene interaction pathway for 61 known disease genes of coronary artery disease (CAD), which contained 46 disease-risk modules and 182 interaction relationships. As demonstrated, disease genes associate through prescribed communication protocols of common biological functions and pathways.
CONCLUSIONS/SIGNIFICANCE: Our analysis was proved to be coincident with our primary hypothesis that disease genes of complex diseases interact with their neighbors in a cooperative manner, associate with each other through shared biological functions and pathways of disease-risk modules, and finally cause dysfunctions of a series of biological processes in molecular networks. We hope our paradigm could be a promising method to identify disease gene interaction pathways for other types of complex diseases, affording additional clues in the pathogenesis of complex diseases.
协同作用的疾病基因在复杂疾病的发生过程中起着至关重要的作用，但如何分析和表示它们的关联仍然是一个悬而未决的问题。传统的方法未能表示疾病基因在复杂疾病的发病机制中相互关联的直接生物学证据。分子网络被认为是“一种生物系统的形式”，由一组相互作用的生物模块（功能模块或途径）组成，这个概念为解决这个问题提供了一个有前途的思路。
方法/主要发现：在本文中，我们假设疾病基因可能通过分子网络中生物模块之间的关联而相互关联。然后，我们引入了一种新的疾病基因相互作用途径表示和分析范例，并成功地确定了冠心病（CAD）61 个已知疾病基因的疾病基因相互作用途径，其中包含 46 个疾病风险模块和 182 个相互作用关系。结果表明，疾病基因通过常见生物功能和途径的预定通信协议相互作用。
结论/意义：我们的分析证明与我们的主要假设一致，即复杂疾病的疾病基因以协同方式相互作用，通过疾病风险模块的共享生物学功能和途径相互关联，最终导致分子网络中一系列生物学过程的功能障碍。我们希望我们的范例可以成为识别其他类型复杂疾病的疾病基因相互作用途径的一种有前途的方法，为复杂疾病的发病机制提供额外的线索。
