A DNA methylation network interaction measure, and detection of network oncomarkers.
A DNA methylation network interaction measure, and detection of network oncomarkers.
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DOI：
10.1371/journal.pone.0084573
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zaikin A
中科院分区：
文献类型：
--
作者：
Bartlett TE;Olhede SC;Zaikin A
包括DNA甲基化在内的表观遗传过程越来越被认为在癌症等慢性疾病中起着重要作用。DNA甲基化模式为直接基于DNA测量而不是不稳定的RNA测量开发预后测量提供了一条途径。在网络环境中，开发了一种新的基于DNA甲基化的协调基因相互作用行为的测量方法。研究表明，这一措施很好地反映了在相同的网络相互作用中与基因表达相关的共调节行为（在mRNA水平上）。该测量是针对单个患者/样本中的基因对定义的，在与不同癌症类型相关的几个独立数据集中，与独立于已知预后临床特征的总体生存结果相关。总共分析了来自9个不同癌症实体的1600多个样本中的5亿多个CpGs。研究发现，与生存显著相关的基因对相互作用组确定了统计上显著的子网络模块。许多这些子网络模块被证明与预定义的基因集有很强的生物学相关性，如免疫功能、伤口愈合、线粒体功能和map -激酶信号传导。特别是，伤口愈合模块对应于导致预后较差的基因之间协调相互作用行为的增加，免疫模块对应于导致预后较差的基因之间协调相互作用行为的减少。这种方法在定义基于dna的癌症生物标志物方面具有很大的潜力。这种生物标记物自然可以通过利用迅速扩大的网络科学知识库进一步开发。
Epigenetic processes–including DNA methylation–are increasingly seen as having a fundamental role in chronic diseases like cancer. DNA methylation patterns offer a route to develop prognostic measures based directly on DNA measurements, rather than less-stable RNA measurements. A novel DNA methylation-based measure of the co-ordinated interactive behaviour of genes is developed, in a network context. It is shown that this measure reflects well the co-regulatory behaviour linked to gene expression (at the mRNA level) over the same network interactions. This measure, defined for pairs of genes in a single patient/sample, associates with overall survival outcome independent of known prognostic clinical features, in several independent data sets relating to different cancer types. In total, more than half a billion CpGs in over 1600 samples, taken from nine different cancer entities, are analysed. It is found that groups of gene-pair interactions which associate significantly with survival identify statistically significant subnetwork modules. Many of these subnetwork modules are shown to be biologically relevant by strong correlation with pre-defined gene sets, such as immune function, wound healing, mitochondrial function and MAP-kinase signalling. In particular, the wound healing module corresponds to an increase in co-ordinated interactive behaviour between genes for worse prognosis, and the immune module corresponds to a decrease in co-ordinated interactive behaviour between genes for worse prognosis. This measure has great potential for defining DNA-based cancer biomarkers. Such biomarkers could naturally be developed further, by drawing on the rapidly expanding knowledge base of network science.
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影响因子：
2
作者：
Davies PC;Lineweaver CH
通讯作者：
Lineweaver CH
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3.7
作者：
Bartlett TE;Zaikin A;Olhede SC;West J;Teschendorff AE;Widschwendter M
通讯作者：
Widschwendter M
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y