基于基因表达数据和蛋白质相互作用网络构建用于白血病准确预测的网络标志物
首发时间:2015-11-30
摘要:白血病是一种复杂疾病,具有多种亚型,同时伴有较高的死亡率,因此寻找用于预测白血病的分子标志物十分迫切。一般认为网络标志物相比单个标志物具有更强的鲁棒性,更加适应不同的个体情况。本文利用基于网络分析的方法构建白血病诊断的网络生物标志物。首先利用PINA数据库和GeneGo数据库重建白血病特异性蛋白质相互作用网络,进一步整合六组基因表达数据,分析识别白血病相关的模块标记物。通过不断迭代筛选合并,最终得到包含97个基因和399条映射关系的网络标志物。对该网络标志物进行性能评价,信号通路富集分析显示,该网络标志物主要富集在癌症相关通路。SVM 分类结果表明该网络标志物可以有效的区分白血病正常样本和疾病样本,准确率达0.94,这为白血病的临床诊断提供了一个有效方法,也有助于进一步了解和阐释白血病发生发展的分子机制。
关键词: 生物信息学 网络标志物 基因表达数据 蛋白质相互作用 综合分析 诊断白血病
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Network biomarker constructed from gene expression and protein-protein interaction data for accurate prediction of leukemia
Abstract:Leukemia is a leading cause of cancer deaths in the developed countries. Great efforts have been undertaken in search of diagnostic biomarkers of leukemia. However, leukemia is highly complex and heterogeneous, involving interaction among multiple molecular components. Individual molecules are not necessarily sensitive diagnostic indicators. Network biomarkers are considered to be robust to heterogeneity and outperform individual molecules in disease characterization. We applied an integrative approach that identifies active network modules as putative biomarkers for leukemia diagnosis. We first reconstructed the leukemia-specific PPI network using protein-protein interactions from the Protein Interaction Network Analysis (PINA) and protein annotations from GeneGo. The network was further integrated with gene expression profiles to identify active modules with leukemia relevance. Finally, the candidate network-based biomarker was evaluated for the diagnosing performance.A network of 97 genes and 399 interactions was identified for accurate diagnosis of leukemia. Functional enrichment analysis revealed that the network biomarker was enriched in pathways in cancer. The network biomarker could effectively discriminate leukemia samples from the normal controls with an accuracy of 0.94.So this network biomarker provides a useful tool to diagnose leukemia and also aids in further understanding the molecular basis of leukemia.?????
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基于基因表达数据和蛋白质相互作用网络构建用于白血病准确预测的网络标志物
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