The network properties of myelodysplastic syndromes pathogenesis revealed by an integrative systems biological method.
The network properties of myelodysplastic syndromes pathogenesis revealed by an integrative systems biological method.
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综合系统生物学方法揭示骨髓增生异常综合征发病机制的网络特性。
DOI：
10.1039/c1mb05018d
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发表时间：
2011
影响因子：
--
通讯作者：
Chang,Chung-Che
中科院分区：
文献类型：
--
作者：
Ren,Xianwen;Zhou,Xiaobo;Chang,Chung-Che
深入了解复杂疾病的分子机制是当前生物医学研究的重要课题。然而，与单基因疾病不同，许多复杂疾病的高度异质性阻碍了科学家对病因的准确理解。在这项研究中，我们使用骨髓增生异常综合征（MDS），造血干细胞的克隆性疾病的异质性家庭，作为一个通用的模型，探索复杂疾病的异质性的网络特性。首先，静态生物信息学分析表明，尽管MDS的巨大的异质性，其临床特性可以很好地解释MDS相关基因在人类相互作用组的本地属性。在此基础上，我们设计了一种新的系统生物学方法，将流式细胞术、基因分型、基因表达谱分析、表达数量性状位点（eQTLs）定位和途径推断相结合，对一个真实的MDS群体的遗传异常传播模式进行了研究。我们构建了一个MDS疾病基因网络，揭示了MDS异质性的网络基础。我们提出的管道和结果暗示的含义可能有助于其他复杂疾病的研究。
Insight into the molecular mechanism of complex diseases is an important topic in the current bio-medical research. However, different from the single-gene disorders, high heterogeneity of many of the complex diseases prevents scientists from the exact understanding of the etiology. In this study, we used Myelodysplastic Syndromes (MDSs), a heterogeneous family of clonal disorders of hematopoietic stem cells, as a general model to explore the network properties of the heterogeneity of complex diseases. First, static bioinformatics analysis suggests that despite the huge heterogeneity of MDSs, their clinical properties can be explained well by the local properties of MDS-related genes on the human interactome. Then we design a novel systems biological method to explore the pattern of genetic abnormality propagation of a real MDS cohort by integrating flowcytometry, genotyping, gene expression profiling, expression quantitative trait loci (eQTLs) mapping and pathway inference. We constructed a MDS disease gene network which suggests the network basis of the heterogeneity of MDSs. The pipeline we proposed and the implication the results suggest may be helpful in the research of other complex diseases.