Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases

doi:10.1371/journal.pcbi.1000521

CSpace > 应用数学研究所

	Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases
	Wang, Jiguang 1,2; Zhang, Shihua1 ; Wang, Yong1 ; Chen, Luonan 3,4; Zhang, Xiang-Sun1
	2009-09-01
发表期刊	PLOS COMPUTATIONAL BIOLOGY
ISSN	1553-7358
卷号	5 期号:9 页码:12
摘要	One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.
DOI	10.1371/journal.pcbi.1000521
语种	英语
资助项目	National Natural Science Foundation of China[10631070] ; National Natural Science Foundation of China[10801131] ; Chinese Academy of Sciences[kjcx-yw-s7] ; Ministry of Science and Technology, China[2006CB503905] ; Innovation Program of Shanghai Municipal Education Commission[09ZZ93]
WOS研究方向	Biochemistry & Molecular Biology ; Mathematical & Computational Biology
WOS类目	Biochemical Research Methods ; Mathematical & Computational Biology
WOS记录号	WOS:000270800100010
出版者	PUBLIC LIBRARY SCIENCE
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/8964
专题	应用数学研究所
通讯作者	Wang, Jiguang
作者单位	1.Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China 3.Shanghai Univ, Inst Syst Biol, Shanghai, Peoples R China 4.Osaka Sangyo Univ, Dept Elect Engn & Elect, Osaka, Japan
推荐引用方式 GB/T 7714	Wang, Jiguang,Zhang, Shihua,Wang, Yong,et al. Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases[J]. PLOS COMPUTATIONAL BIOLOGY,2009,5(9):12.
APA	Wang, Jiguang,Zhang, Shihua,Wang, Yong,Chen, Luonan,&Zhang, Xiang-Sun.(2009).Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases.PLOS COMPUTATIONAL BIOLOGY,5(9),12.
MLA	Wang, Jiguang,et al."Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases".PLOS COMPUTATIONAL BIOLOGY 5.9(2009):12.