基于全局角度网络策略的复杂疾病风险通路识别
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哈尔滨医科大学生物信息科学与技术学院,哈尔滨医科大学生物信息科学与技术学院,哈尔滨医科大学生物信息科学与技术学院,哈尔滨医科大学生物信息科学与技术学院,哈尔滨医科大学生物信息科学与技术学院,哈尔滨医科大学生物信息科学与技术学院

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国家自然科学基金(31200996), 黑龙江省教育厅项目(12531295)和哈尔滨医科大学于维汉院士杰出青年培养基金资助


A Network-based Strategy From The Global Perspective for Identification of Risk Pathways in Complex Diseases
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College of Bioinformatics Science and Technology,Harbin Medical University,College of Bioinformatics Science and Technology,Harbin Medical University,College of Bioinformatics Science and Technology,Harbin Medical University,College of Bioinformatics Science and Technology,Harbin Medical University,College of Bioinformatics Science and Technology, Harbin Medical University,College of Bioinformatics Science and Technology,Harbin Medical University

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This work was supported by grants from The National Natural Science Foundation of China (31200996), The Education Department Project of Heilongjiang Province (12531295), and Yu Weihan Outstanding Youth Training Fund of Harbin Medical University

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    摘要:

    复杂疾病的发生发展与机体内生物学通路的功能紊乱有密切联系,从高通量数据出发,利用计算机辅助方法来研究疾病与通路间的关系具有重要意义.本文提出了一个新的基于网络的全局性通路识别方法.该方法利用蛋白质互作信息和通路的基因集组成信息构建复杂的蛋白质-通路网.然后,基于表达谱数据,通过随机游走算法从全局层面优化疾病风险通路.最终,通过扰动方式识别统计学显著的风险通路.将该网络运用于结肠直肠癌风险通路识别,识别出15个与结肠直肠癌发生与发展过程显著相关的通路.通过与其他通路识别方法(超几何检验,SPIA)相比较,该方法能够更有效识别出疾病相关的风险通路.

    Abstract:

    The initiation and progression of complex diseases have a close relationship with dysfunction of biological pathways in our body. Developing computational techniques to study the relationship between diseases and pathways through high-throughput data has essential biological significance. However, the traditional identification approaches of pathways which are significantly related to experiment conditions usually reduce pathways to gene sets. It is obvious that these methods do not consider the interactions between genes and the different roles that genes play in pathways, and they don't fully mine pathway information. Therefore we integrated protein-protein interaction information and gene weights into pathway analysis, and constructed a protein-pathway network which contains information in protein-protein interactions and pathways. We then scored pathways by random walk algorithm to optimize disease risk pathways. Finally, the statistically significant pathway can be identified through permutation method. We applied the network to a colorectal cancer dataset, and finally identified fifteen pathways which are significantly related to the development of this disease. Compared with other pathway identification methods (hypergeometric test and SPIA), our approach can effectively identify risk pathways related to complex diseases. In order to test the stability of our method in identifying risk pathways related to diseases, we used our method to identify risk pathways by using another colorectal cancer dataset. We found that the identified results can prove the stability of our method.

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邓莉莉,许艳军,张春龙,姚茜岚,冯丽,李春权.基于全局角度网络策略的复杂疾病风险通路识别[J].生物化学与生物物理进展,2015,42(3):286-296

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历史
  • 收稿日期:2014-04-14
  • 最后修改日期:2015-01-12
  • 接受日期:2015-01-15
  • 在线发布日期: 2015-03-24
  • 出版日期: 2015-03-20