The library is a collection of R classes and functions related to receiver operating characteristic (ROC) curves. These functions are targeted at the use of ROC analysis with DNA microarrays, as discussed in work of MS Pepe, G Anderson and colleagues at U Washington Seattle Biostatistics (unpublished report). Other open source software for ROC analysis in the S language has been distributed by Beth Atkinson of the Mayo Clinic.

ROC curves illustrate the performance of a classification procedure
based on dichotomous interpretation of a continuous marker. Suppose
the true state of an item is either `$+$' or`

\(-\)’. The item’s marker
value is compared to a threshold, and the item is classified as
positive or negative depending on whether the marker value is greater
than or less than the threshold. For a fixed threshold \(t\), the
procedure has a sensitivity Pr(marker \(\geq t\) \(|\)true class\(=+\)) and
specificity Pr(marker \(< t\) \(|\)true class\(=-\)). The ROC curve is the
locus of values \((x, y) = (1-\mbox{spec}, \mbox{sens})\).

Let’s verify:

<<>>= library(ROC) print(getClass(“rocc”)) @

For creation of an ROC curve object (an instance of class ), the function is available. The name is chosen to indicate that this is a provisional definition based on a scalar marker.

is defined as follows: <<>>= print(rocdemo.sca) @

The argument is the vector of actual states of the objects being classified, and it must be a vector of binary indicators. The argument is the vector of marker values. The argument is the classification rule. This must be a function of two arguments, and the following is an obvious approach:

<<>>= print(dxrule.sca) @

To begin working with ROC curves in R, you can proceed as follows.

<<>>= set.seed(123) state <- c(0,0,0,0,0,1,1,1,1,1,0,0,0,0,0,1,1,1,1,1) markers <- c(1,2,1,1,2,3,3,4,2,1,1,3,2,3,2,4,5,2,3,4)+runif(20,-1,1) roc1 <- rocdemo.sca( truth=state, data=markers, rule=dxrule.sca ) @

@ @The area under the ROC curve is well known to be equivalent to the numerator of the Mann-Whitney U statistic comparing the marker distributions among positive and negative items. Even if the overall area is not very large, the existence of threshold values yielding sensitivities markedly greater than the false positive rate can be of interest. The sensitivity at a false positive rate \(t\) is denoted ROC(\(t\)); the AUC = \(\int_0^1 ROC(u)du\). Finally, the partial AUC to a false positive rate \(s\) is denoted pAUC(\(s\)) = \(\int_0^s ROC(u)du\).

<<>>= auc <- AUC(roc1); print(auc) paucp4 <- pAUC(roc1,.4); print(paucp4) rocp3 <- ROC(roc1,.3); print(rocp3)

@ Note that the definition of the AUC uses a naive trapezoidal rule. This is faster than . However, functions AUCi and pAUCi that use the more accurate integrate() function are available.

<<>>= print(trapezint)

@

See the Biobase package for a discussion of the class, which represents a collection of microarrays. Given a dichotomous element from the slot, an AnnotatedDataFrame, of an object, an ROC curve may be defined using the expression levels of any gene as the vector of marker values.

We confine activities to the first 50 genes in sample.ExpressionSet so that this vignette is computable in reasonable CPU time.

<<>>= library(Biobase) data(sample.ExpressionSet) myauc <- function(x) { dx <- as.numeric(sex) - 1 # phenoData is installed AUC( rocdemo.sca( truth=dx, data=x, rule=dxrule.sca ) ) } mypauc1 <- function(x) { dx <- as.numeric(sex) - 1 pAUC( rocdemo.sca( truth=dx, data=x, rule=dxrule.sca ), .1 ) }

allAUC <- esApply( sample.ExpressionSet[1:50,], 1, myauc )

allpAUC1 <- esApply( sample.ExpressionSet[1:50,], 1, mypauc1 )

print(featureNames(sample.ExpressionSet[1:50,])[order(allAUC, decreasing = TRUE)[1]])

print(featureNames(sample.ExpressionSet[1:50,])[order(allpAUC1, decreasing = TRUE)[1]])

@

Pepe et al indicate that rankings based on ROC functionals are of interest, and that uncertainty in rankings can be exposed by resampling tissues. Working with s, this is easy to carry out. (We use a very small number of resamplings (5) to get through this in a reasonable execution time.)

<<>>= nResamp <- 5 nTiss <- ncol(exprs(sample.ExpressionSet)) nGenes <- nrow(exprs(sample.ExpressionSet[1:50,])) out <- matrix(NA,nr=nGenes, nc=nResamp) set.seed(123) for (i in 1:nResamp) { TissInds <- sample(1:nTiss, size=nTiss, replace=TRUE) out[,i] <- esApply( sample.ExpressionSet[1:50,TissInds], 1, myauc ) } rout <- apply(out,2,rank)

@ Each row of the matrix is a sample from the bootstrap distribution of AUC ranks for the corresponding gene.

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