A matrix rank based concordance index for evaluating and detecting conditional specific co-expressed gene modules.

A matrix rank based concordance index for evaluating and detecting conditional specific co-expressed gene modules.
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基于矩阵等级的一致性指数,用于评估和检测条件特定的共表达基因模块。

DOI:
10.1186/s12864-016-2912-y
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发表时间:
2016-08-22
期刊:
影响因子:
4.4
通讯作者:
Huang K
Huang K
中科院分区:
生物学2区
文献类型:
--
作者:
Han Z;Zhang J;Sun G;Liu G;Huang K

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基因共表达网络分析(GCNA)在生物信息学和生物医学研究中有着广泛的应用,如基因功能预测、蛋白质相互作用推断、疾病标记识别和拷贝数变异发现等。目前,对于共表达基因模块应满足的数学条件缺乏严格的分析。本文提出了一种基于线性代数的集中一致性指数(CCI)来评价基因共表达网络分析中共表达基因模块的一致性。CCI可用于评估共表达网络分析算法的性能以及用于检测特定条件的共表达模块。我们将CCI应用于肺癌特异性基因模块的检测。模拟表明,CCI是评估一组共表达基因一致性的一个强有力的指标。应用于肺癌数据集揭示了有趣的潜在肿瘤特异性基因变化,包括CNV,甚至基因融合的迹象。需要更深入的分析才能理解所有这些条件特异性共表达关系的分子机制。CCI可用于评估共表达网络分析算法的性能,以及用于检测条件特定的共表达模块。与基于皮尔逊相关系数的密度相比,它对异常值和干扰模块具有更强的鲁棒性。
 Gene co-expression network analysis (GCNA) is widely adopted in bioinformatics and biomedical research with applications such as gene function prediction, protein-protein interaction inference, disease markers identification, and copy number variance discovery. Currently there is a lack of rigorous analysis on the mathematical condition for which the co-expressed gene module should satisfy. In this paper, we present a linear algebraic based Centralized Concordance Index (CCI) for evaluating the concordance of co-expressed gene modules from gene co-expression network analysis. The CCI can be used to evaluate the performance for co-expression network analysis algorithms as well as for detecting condition specific co-expression modules. We applied CCI in detecting lung tumor specific gene modules. Simulation showed that CCI is a robust indicator for evaluating the concordance of a group of co-expressed genes. The application to lung cancer datasets revealed interesting potential tumor specific genetic alterations including CNVs and even hints for gene-fusion. Deeper analysis required for understanding the molecular mechanisms of all such condition specific co-expression relationships. The CCI can be used to evaluate the performance for co-expression network analysis algorithms as well as for detecting condition specific co-expression modules. It is shown to be more robust to outliers and interfering modules than density based on Pearson correlation coefficients.
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