ebam: Empirical Bayes Analysis of Microarrays

Description Usage Arguments Value Author(s) References See Also Examples

Description

Performs an Empirical Bayes Analysis of Microarrays (EBAM). It is possible to perform one and two class analyses using either a modified t-statistic or a (standardized) Wilcoxon rank statistic, and a multiclass analysis using a modified F-statistic. Moreover, this function provides a EBAM procedure for categorical data such as SNP data and the possibility to employ an user-written score function.

Usage

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  ebam(x, cl, method = z.ebam, delta = 0.9, which.a0 = NULL, 
       control = ebamControl(), gene.names = dimnames(x)[[1]],
       ...)

Arguments

x

either a matrix, a data frame or an ExpressionSet object, or the output of find.a0, i.e.\ an object of class FindA0. Can also be a list (if method = chisq.ebam or method = trend.ebam). For the latter case, see chisq.ebam. If x is not a FindA0 object, then each row of x (or exprs(x), respectively) must correspond to a variable (e.g., a gene or a SNP), and each column to a sample.

cl

a specification of the class labels of the samples. Ignored if x is a FindA0 object. Needs not to be specified if x is a list.

Typically, cl is specified by a vector of length ncol(x). In the two class paired case, cl can also be a matrix with ncol(x) rows and 2 columns. If x is an ExpressionSet object, cl can also be a character string naming the column of pData(x) that contains the class labels of the samples.

In the one-class case, cl should be a vector of 1's.

In the two class unpaired case, cl should be a vector containing 0's (specifying the samples of, e.g., the control group) and 1's (specifying, e.g., the case group).

In the two class paired case, cl can be either a numeric vector or a numeric matrix. If it is a vector, then cl has to consist of the integers between -1 and -n/2 (e.g., before treatment group) and between 1 and n/2 (e.g., after treatment group), where n is the length of cl and k is paired with -k, k=1,…,n/2. If cl is a matrix, one column should contain -1's and 1's specifying, e.g., the before and the after treatment samples, respectively, and the other column should contain integer between 1 and n/2 specifying the n/2 pairs of observations.

In the multiclass case and if method = chisq.ebam or method = trend.ebam, cl should be a vector containing integers between 1 and g, where g is the number of groups. In the two latter cases, cl needs not to be specified, if x is a list. For details, see chisq.ebam.

For examples of how cl can be specified, see the manual of siggenes.

method

a character string or name specifying the method or function that should be used in the computation of the expression score z.

If method = z.ebam, a modified t- or F-statistic, respectively, will be computed as proposed by Efron et al. (2001).

If method = wilc.ebam, a (standardized) Wilcoxon sum / signed rank statistic will be used as expression score.

For an analysis of categorical data such as SNP data, method can be set to chisq.ebam. In this case, Pearson's Chi-squared statistic is computed for each row.

If the variables are ordinal and a trend test should be applied (e.g., in the two-class case, the Cochran-Armitage trend test), method = trend.ebam can be employed.

It is also possible to employ an user-written function for computing an user-specified expression score. For details, see the vignette of siggenes.

delta

a numeric vector consisting of probabilities for which the number of differentially expressed genes and the FDR should be computed, where a gene is called differentially expressed if its posterior probability is larger than Delta.

which.a0

an integer between 1 and the length of quan.a0 of find.a0. If NULL, the suggested choice of find.a0 is used. Ignored if x is a matrix, data frame or ExpressionSet object.

control

further arguments for controlling the EBAM analysis. For these arguments, see ebamControl.

gene.names

a vector of length nrow(x) specifying the names of the variables. By default, the row names of the matrix / data frame comprised by x are used.

...

further arguments of the specific EBAM methods. If method = z.ebam, see z.ebam. If method = wilc.ebam, see wilc.ebam. If method = chisq.ebam, see chisq.ebam.

Value

An object of class EBAM.

Author(s)

Holger Schwender, [email protected]

References

Efron, B., Tibshirani, R., Storey, J.D. and Tusher, V. (2001). Empirical Bayes Analysis of a Microarray Experiment. JASA, 96, 1151-1160.

Schwender, H., Krause, A., and Ickstadt, K. (2006). Identifying Interesting Genes with siggenes. RNews, 6(5), 45-50.

Storey, J.D. and Tibshirani, R. (2003). Statistical Significance for Genome-Wide Studies. Proceedings of the National Academy of Sciences, 100, 9440-9445.

See Also

EBAM-class, find.a0, z.ebam, wilc.ebam, chisq.ebam

Examples

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## Not run: 
  # Load the data of Golub et al. (1999) contained in the package multtest.
  data(golub)
  
  # golub.cl contains the class labels.
  golub.cl
  
  # Perform an EBAM analysis for the two class unpaired case assuming
  # unequal variances. Specify the fudge factor a0 by the suggested
  # choice of find.a0
  find.out <- find.a0(golub, golub.cl, rand = 123)
  ebam.out <- ebam(find.out)
  ebam.out
    
  # Since a0 = 0 leads to the largest number of genes (i.e. the suggested
  # choice of a0), the following leads to the same results as the above
  # analysis (but only if the random number generator, i.e. rand, is set
  # to the same number).
  ebam.out2 <- ebam(golub, golub.cl, a0 = 0, fast = TRUE, rand = 123)
  ebam.out2

  # If fast is set to TRUE in ebam, a crude estimate of the number of
  # falsely called genes is used (see the help file for z.ebam). This
  # estimate is always employed in find.a0. 
  # The exact number is used in ebam when performing
  ebam.out3 <- ebam(golub, golub.cl, a0 = 0, rand = 123)
  ebam.out3  

  # Since this is the recommended way, we use ebam.out3 at the end of
  # the Examples section for further analyses.



  # Perform an EBAM analysis for the two class unpaired case assuming
  # equal group variances. Set a0 = 0, and use B = 50 permutations
  # of the class labels.
  ebam.out4 <- ebam(golub, golub.cl, a0 = 0, var.equal = TRUE, B = 50,
     rand = 123)
  ebam.out4
    
  # Perform an EBAM analysis for the two class unpaired cased assuming
  # unequal group variances. Use the median (i.e. the 50% quantile)
  # of the standard deviations of the genes as fudge factor a0. And
  # obtain the number of genes and the FDR if a gene is called 
  # differentially when its posterior probability is larger than
  # 0.95.
  ebam.out5 <- ebam(golub, golub.cl, quan.a0 = 0.5, delta = 0.95,
     rand = 123)
  ebam.out5
    
  # For the third analysis, obtain the number of differentially
  # expressed genes and the FDR if a gene is called differentially
  # expressed if its posterior probability is larger than 0.8, 0.85,
  # 0.9, 0.95.
  print(ebam.out3, c(0.8, 0.85, 0.9, 0.95))
    
  # Generate a plot of the posterior probabilities for delta = 0.9.
  plot(ebam.out3, 0.9)
    
  # Obtain the list of genes called differentially expressed if their
  # posterior probability is larger than 0.99, and gene-specific 
  # statistics for these variables such as their z-value and their
  # local FDR.
  summary(ebam.out3, 0.99)

## End(Not run)

siggenes documentation built on May 2, 2018, 6:07 p.m.