Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.
Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.
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DOI：
10.1371/journal.pone.0020284
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Furlong LI
中科院分区：
文献类型：
--
作者：
Bauer-Mehren A;Bundschus M;Rautschka M;Mayer MA;Sanz F;Furlong LI
长期以来，科学家们一直试图了解疾病的分子机制，以设计预防和治疗策略。对于某些疾病，很明显，仅仅获得疾病相关基因的目录是不够的，还需要揭示细胞中分子网络的破坏如何引起疾病表型。此外，由于现有的信息空前丰富，即使获得这样的目录也极为困难。我们通过整合涵盖疾病不同生物医学方面的多个来源的关联，开发了一个全面的基因-疾病关联数据库。特别是，我们专注于人类遗传疾病，包括孟德尔，复杂和环境疾病的现有知识。为了评估人类疾病模块化的概念，我们通过网络拓扑和功能注释分析对人类基因-疾病网络的涌现特性进行了系统研究。结果表明，人类疾病的遗传起源高度共享，并表明对于大多数疾病，包括孟德尔，复杂和环境疾病，存在功能模块。此外，一组核心的生物学途径被发现与大多数人类疾病有关。我们在研究疾病集群时获得了类似的结果，这表明相关疾病可能是由于细胞中常见生物过程的功能障碍而引起的。我们第一次在一个综合的基因-疾病关联数据库中包括孟德尔疾病、复杂疾病和环境疾病，并表明模块化的概念适用于所有疾病。我们还提供了一个功能分析的疾病相关模块提供重要的新的生物学见解，这可能不会被发现时，考虑每个基因-疾病关联库独立。因此，我们提出了一个合适的框架来研究遗传和环境因素（如药物）如何导致疾病。本研究中使用的基因-疾病网络和部分分析可在http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download上获得。
Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download.
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影响因子：
3.7
作者：
Cerami E;Demir E;Schultz N;Taylor BS;Sander C
通讯作者：
Sander C
影响因子：
3.8
作者：
Argos, Maria;Kibriya, Muhammad G.;Ahsan, Habibul
通讯作者：
Ahsan, Habibul
影响因子：
5.8
作者：
Bauer-Mehren, Anna;Rautschka, Michael;Furlong, Laura I.
通讯作者：
Furlong, Laura I.
DOI：
10.1038/nrg2918
发表时间：
2011-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.5
作者：
Carreira, Suzanne;Goodall, Jane;Goding, Colin R.
通讯作者：
Goding, Colin R.