RRHO (version 1.12.0)

RRHOComparison: Compares two RRHO maps to a third

Description

Comparing two RRHO maps where one of the lists is shared between the two maps as in {RRHO map 1: list1 vs list3} vs {RRHO map 2: list2 vs list3}.

Usage

RRHOComparison(list1, list2, list3,  stepsize, plots = FALSE,  labels, outputdir = NULL, log10.ind)

Arguments

list1

A data.frame from experiment 1 with two columns, column 1 is the `Gene Identifier', column 2 is the signed ranking value (e.g. signed -log10 of p-value, or fold change).

list2

Same as list1.

list3

Same as list1.

stepsize

Integer indicating how many genes to increase by in each algorithm iteration.

labels

Character vector carrying the labels for the outputted plots.

plots

Logical. Should comparisons be plotted?

outputdir

Plot destination directory.

log10.ind

Logical. Should pvalues be reported and plotted in -log10 scale and not -log scale?

Value

A oject including:

hypermat1

Pvalues of comparing list1 to list3.

hypermat2

Pvalues of comparing list2 to list3.

Pdiff

The pvalue of the test for a difference in difference between lists 1-3 and 2-3.

Pdiff.by

Pvalues, corrected for the search over all of the list using Benjamini-Yekutieli.

Details

The difference in {overlap between list1 and list3} compared to the {overlap between list2 and list3}. This is useful for determining if there is a statistically significant difference between two RRHO maps. In other words, this is useful for determining if the overlap between list1 and list3 is statistically different between the overlap between list2 and list3.

RRHO Difference maps are produced by calculating for each pixel the normal approximation of difference in log odds ratio and standard error of overlap between the two RRHO maps. This Z score is then converted to a P-value and corrected for multiple comparisons across pixels [3].

The function will return a RRHO of the significance of overlap between list1 and list3 and list2 and list3. A third RRHO gives the significance of the difference between these two overlap maps.

Note that by default all pvalues are outputted in -log scale. This can be changed with the log10.ind argument.

References

[1] Plaisier, Seema B., Richard Taschereau, Justin A. Wong, and Thomas G. Graeber. "Rank-rank Hypergeometric Overlap: Identification of Statistically Significant Overlap between Gene-Expression Signatures." Nucleic Acids Research 38, no. 17 (September 1, 2010): e169-e169.

[2] Benjamini, Y., and D. Yekutieli. "The Control of the False Discovery Rate in Multiple Testing under Dependency." ANNALS OF STATISTICS 29, no. 4 (2001): 1165-88.

[3] Stein JL*, de la Torre-Ubieta L*, Tian Y, Parikshak NN, Hernandez IA, Marchetto MC, Baker DK, Lu D, Lowe JK, Wexler EM, Muotri AR, Gage FH, Kosik KS, Geschwind DH. "A quantitative framework to evaluate modeling of cortical development by neural stem cells." Manuscript in press at Neuron. (*) Authors contributed equally to this work.

See Also

RRHO

Examples

  size<- 500
  list1<- data.frame(GeneIdentifier=paste('gen',1:size, sep=''), 
  RankingVal=-log(runif(size)))
  list2<- data.frame(GeneIdentifier=paste('gen',1:size, sep=''), 
  RankingVal=-log(runif(size)))
  list3<- data.frame(GeneIdentifier=paste('gen',1:size, sep=''), 
  RankingVal=-log(runif(size)))
  (temp.dir<- tempdir())
  RRHOComparison(list1,list2,list3,
                  stepsize=10,
                  labels=c("list1","list2","list3"),
                  plots=TRUE,
                  outputdir=temp.dir,
                  log10.ind=FALSE)