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Aging effects on DNA methylation modules in human brain and blood tissue
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * One can study module preservation in general networks specified by an adjacency matrix, e.g. protein-protein interaction networks. However, particularly powerful statistics are available for correlation networks weighted correlation networks are particularly useful for detecting subtle changes in connectivity patterns. But the methods are also applicable to unweighted networks (i.e. graphs) Module preservation in different types of networks Several connectivity preservation statistics For general networks, i.e. input adjacency matrices cor.kIM=cor(kIMref,kIMtest) correlation of intramodular connectivity across module nodes cor.ADJ=cor(Aref,Atest) correlation of adjacency across module nodes For correlation networks, i.e. input sets are variable measurements cor.Cor=cor(corref,cortest) cor.kME=cor(kMEref,kMEtest) One can derive relationships among these statistics in case of weighted correlation network Choosing thresholds for preservation statistics based on permutation test For correlation networks, we study 4 density and 4 connectivity preservation statistics that take on values = 1 Challenge: Thresholds could depend on many factors (number of genes, number of samples, biology, expression platform, etc.) Solution: Permutation test. Repeatedly permute the gene labels in the test network to estimate the mean and standard deviation under the null hypothesis of no preservation. Next we calculate a Z statistic Gene modules in Adipose Permutation test for estimating Z scores For each preservation measure we report the observed value and the permutation Z score to measure significance. Each Z score provides answer to “Is the module significantly better than a random sample of genes?” Summarize the individual Z scores into a composite measure called Z.summary Zsummary 2 indicates no preservation, 2Zsummary10 weak to moderate evidence of preservation, Zsummary10 strong evidence Composite stat
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