@@ -1,7 +1,7 @@

 Package: ROntoTools

 Type: Package

 Title: R Onto-Tools suite

-Version: 1.1.0

+Version: 1.1.2

 Author: Calin Voichita <calin@wayne.edu> and Sorin Draghici <sorin@wayne.edu>

 Maintainer: Calin Voichita <calin@wayne.edu>

 Description: Suite of tools for functional analysis

@@ -1,6 +1,6 @@

 export(alpha1MR)

 export(alphaMLG)

-export(compute.fischer)

+export(compute.fisher)

 export(compute.normalInv)

 export(keggPathwayGraphs)

 export(keggPathwayNames)

@@ -16,7 +16,7 @@ exportMethods(plot)

 exportMethods(Summary)

 import(boot)

 import(graph)

-import(KEGGgraph)

 import(KEGGREST)

+import(KEGGgraph)

 import(parallel)

 importMethodsFrom(KEGGgraph)

@@ -1,3 +1,8 @@

+VERSION 1.2.0

+--------

+

+* add the ability to analyze gene sets (pathways with no interaction) using only over-representation

+* bug fixes: plot boundaries, etc.

 VERSION 1.0.0

 --------

@@ -63,7 +63,8 @@ setClass("pePathway",

                         ref = "character",

                         boot = "ANY",

                         Pert = "numeric",

-                        Acc = "numeric"

+                        Acc = "numeric",

+                        asGS = "logical"

          ), 

          prototype(map = new("graphNEL")

          )

@@ -3,7 +3,7 @@

 #' 

 #' @usage Summary(x, pathNames = NULL, totalAcc = TRUE, totalPert = TRUE, normalize = TRUE, 

 #'  pPert = TRUE, pAcc = TRUE, pORA = TRUE, 

-#'  comb.pv = c("pPert", "pORA"), comb.pv.func = compute.fischer,

+#'  comb.pv = c("pPert", "pORA"), comb.pv.func = compute.fisher,

 #'  order.by = "pComb", adjust.method = "fdr")

 #' 

 #' @param x Pathways-Express result object obtained using \code{\link{pe}}

@@ -55,7 +55,7 @@

 setMethod("Summary", c("x" = "peRes"),

           function(x, pathNames = NULL, totalAcc = TRUE, totalPert = TRUE, normalize = TRUE, 

                    pPert = TRUE, pAcc = TRUE, pORA = TRUE, 

-                   comb.pv = c("pPert", "pORA"), comb.pv.func = compute.fischer,

+                   comb.pv = c("pPert", "pORA"), comb.pv.func = compute.fisher,

                    order.by = "pComb", adjust.method = "fdr")

           {  

             ifelse <- function(test, trueCase, falseCase){

@@ -67,19 +67,19 @@ setMethod("Summary", c("x" = "peRes"),

             {

               pStats <- NULL

-              pStats$totalAcc <- ifelse(totalAcc, get.totalAcc(pePath), NULL)

-              pStats$totalPert <- ifelse(totalPert, get.totalPert(pePath), NULL)

+              pStats$totalAcc <- ifelse(totalAcc, ifelse(!pePath@asGS, get.totalAcc(pePath), NA), NULL)

+              pStats$totalPert <- ifelse(totalPert, ifelse(!pePath@asGS, get.totalPert(pePath), NA), NULL)

-              pStats$totalAccNorm <- ifelse(totalAcc & normalize, get.totalAccNorm(pePath), NULL)

-              pStats$totalPertNorm <- ifelse(totalPert & normalize, get.totalPertNorm(pePath), NULL)

+              pStats$totalAccNorm <- ifelse(totalAcc & normalize, ifelse(!pePath@asGS, get.totalAccNorm(pePath), NA), NULL)

+              pStats$totalPertNorm <- ifelse(totalPert & normalize, ifelse(!pePath@asGS, get.totalPertNorm(pePath), NA), NULL)

-              pStats$pPert <- ifelse(pPert, compute.pPert(pePath), NULL)

-              pStats$pAcc <- ifelse(pAcc, compute.pAcc(pePath), NULL)

+              pStats$pPert <- ifelse(pPert, ifelse(!pePath@asGS, compute.pPert(pePath), NA), NULL)

+              pStats$pAcc <- ifelse(pAcc, ifelse(!pePath@asGS, compute.pAcc(pePath), NA), NULL)

               pStats$pORA <- ifelse(pORA & !x@cutOffFree, compute.pORA(pePath, length(x@input), length(x@ref)), NULL)

               pStats$pComb <- ifelse(!is.null(comb.pv) & !any(is.null(pStats[comb.pv])), 

-                                     as.numeric(comb.pv.func(unlist(pStats[comb.pv]))), NULL)

+                                     ifelse(!any(is.na(pStats[comb.pv])), as.numeric(comb.pv.func(unlist(pStats[comb.pv]))), NA), NULL)

               return(unlist(pStats))

             }

@@ -167,7 +167,7 @@ keggPathwayGraphs <- function(organism = "hsa",

   pathwayGraphs <- pathwayGraphs[!sapply(pathwayGraphs, is.null)]

   if (defaultParameters)

-    save(pathwayGraphs, paste(system.file("extdata",package="ROntoTools"), "/kpgDefault.RData", sep = ""))

+    save(pathwayGraphs, file = paste(system.file("extdata",package="ROntoTools"), "/kpgDefault.RData", sep = ""))

   return(pathwayGraphs)

 }

@@ -194,9 +194,15 @@ pe.boot <- function(g, x, ref, nboot, all.genes = F)

                       input = x[names(x) %in% nodes(g)],

                       ref = ref[ref %in% nodes(g)])

-  if (is.null(inv) | (length(pePath@input) == 0))

+  if (length(pePath@input) == 0)

     return(NULL)

+  if (is.null(inv))

+  {

+    pePath@asGS <- TRUE

+    return(pePath)

+  }

+  

   # same number of DE genes at any position in the pathway 

   # (given by the gene from the pathway in the reference)

   ran.gen.de <- function(x, l)  {

@@ -226,7 +232,8 @@ pe.boot <- function(g, x, ref, nboot, all.genes = F)

   xx[names(pePath@input)] <- pePath@input  

   pePath@Pert = (inv %*% xx)[,1];

   pePath@Acc = pePath@Pert - xx

-    

+  pePath@asGS <- FALSE

+  

   return(pePath) 

 }

@@ -92,7 +92,9 @@ setMethod("plot", signature(x="pePathway", y="character"),

                      tB <- (tB - mean(allB)) / sd(allB)

                      allB <- (allB - mean(allB)) / sd(allB)

-                     plot(density(allB), xlab = y, main = main, ...)

+                     xlim <- c(min(allB, tB), max(allB, tB)) * 1.10

+                     

+                     plot(density(allB, from = xlim[1], to = xlim[2]), xlab = y, main = main, ...)

                      abline(v=0, lwd = .5)

                      abline(v=tB, lwd = 1, col = "red")

@@ -112,7 +114,7 @@ setMethod("plot", signature(x="pePathway", y="character"),

 #' @param y vector of two p-values names to be combined using \code{comb.pv.func} (default: \code{c("pAcc", "pORA")}).

 #' @param ... Arguments to be passed to methods, such as \code{\link{par}}.

 #' @param comb.pv.func the function to combine the p-values - takes as input a vector of p-values 

-#' and returns the combined p-value (default: \code{\link{compute.fischer}}).

+#' and returns the combined p-value (default: \code{\link{compute.fisher}}).

 #' @param adjust.method the name of the method to adjust the p-value (see \code{\link{p.adjust}})

 #' @param threshold corrected p-value threshold

 #' @param eps any value smaller than this will be considered as \code{eps} (default: \code{1e-6}).

@@ -148,7 +150,7 @@ setMethod("plot", signature(x="pePathway", y="character"),

 #' @aliases plot,peRes,missing-method

 #' @export

 setMethod("plot", signature(x="peRes", y="missing"),

-          function(x, y, ... , comb.pv.func = compute.fischer, adjust.method = "fdr", threshold = .05, eps = 1e-6)

+          function(x, y, ... , comb.pv.func = compute.fisher, adjust.method = "fdr", threshold = .05, eps = 1e-6)

           {

             plot(x, y = c("pAcc", "pORA"), ... , comb.pv.func = comb.pv.func, adjust.method = adjust.method,

                  threshold = threshold, eps = eps)

@@ -161,7 +163,7 @@ setMethod("plot", signature(x="peRes", y="missing"),

 #' @aliases plot,peRes,character-method

 #' @export

 setMethod("plot", signature(x="peRes", y="character"),

-          function(x, y, ... , comb.pv.func = compute.fischer, adjust.method = "fdr", threshold = .05, eps = 1e-6)

+          function(x, y, ... , comb.pv.func = compute.fisher, adjust.method = "fdr", threshold = .05, eps = 1e-6)

           {

             st <- Summary(x, comb.pv = y, comb.pv.func = comb.pv.func, adjust.method = adjust.method)

@@ -140,7 +140,10 @@ peNodeRenderInfo <- function(x, y = "Pert",

   nFillColor <- rep(zero.col, length(nodes(x@map)))

   names(nFillColor) <- nodes(x@map)

-  pf <- slot(x, y)

+  pfi <- slot(x, y)

+  pf <- rep(0, length(nodes(x@map)))

+  names(pf) <- nodes(x@map)

+  pf[names(pfi)] <- pfi

   nFillColor[pf <= 0] <- colorRampPalette(c(zero.col,neg.col))(256)[as.numeric(cut(abs(pf[pf<=0]), 256))]                                  

   nFillColor[pf >= 0] <- colorRampPalette(c(zero.col,pos.col))(256)[as.numeric(cut(abs(pf[pf>=0]), 256))]

@@ -14,7 +14,7 @@ addNames <- function(x, nms)

 compute.bootPV <- function(real, dist)

   ( sum(abs(dist - mean(dist)) > abs(real - mean(dist))) + 1 ) / (1 + length(dist))

-#' Combine independent p-values using the Fischer method

+#' Combine independent p-values using the Fisher method

 #' 

 #' @param p a vector of independent p-values

 #' @param eps the minimal p-value considered (all p-values smaller will be set to this value)

@@ -23,15 +23,19 @@ compute.bootPV <- function(real, dist)

 #' 

 #' @author Calin Voichita and Sorin Draghici

 #' 

+#' @references

+#' 

+#' Tarca AL., Draghici S., Khatri P., Hassan SS., Kim J., Kim CJ., Kusanovic JP., Romero R.: "A Signaling Pathway Impact Analysis for Microarray Experiments", 2008, Bioinformatics, 2009, 25(1):75-82.

+#' 

 #' @seealso \code{\link{pe}},\code{\link{compute.normalInv}}

 #' 

 #' @examples

 #' 

 #' p <- c(.1, .01)

-#' compute.fischer(p)

+#' compute.fisher(p)

 #' 

 #' @export

-compute.fischer <- function(p, eps = 1e-6)

+compute.fisher <- function(p, eps = 1e-6)

 {

   stopifnot(any(p >= 0 & p<=1))  

   p[p < eps] <- eps

@@ -49,7 +53,11 @@ compute.fischer <- function(p, eps = 1e-6)

 #' 

 #' @author Calin Voichita and Sorin Draghici

 #' 

-#' @seealso \code{\link{pe}},\code{\link{compute.fischer}}

+#' @references

+#' 

+#' Tarca AL., Draghici S., Romero R.: "A Mmore Specific Method To Combine Perturbation and Over-representation Evidence in Pathway Analysis", PSB 2010 poster.

+#' 

+#' @seealso \code{\link{pe}},\code{\link{compute.fisher}}

 #' 

 #' @examples

 #' 

deleted file mode 100644

@@ -1,26 +0,0 @@

-\name{compute.fischer}

-\alias{compute.fischer}

-\title{Combine independent p-values using the Fischer method}

-\usage{

-  compute.fischer(p, eps = 1e-06)

-}

-\arguments{

-  \item{p}{a vector of independent p-values}

-

-  \item{eps}{the minimal p-value considered (all p-values

-  smaller will be set to this value)}

-}

-\description{

-  Combine independent p-values using the Fischer method

-}

-\examples{

-p <- c(.1, .01)

-compute.fischer(p)

-}

-\author{

-  Calin Voichita and Sorin Draghici

-}

-\seealso{

-  \code{\link{pe}},\code{\link{compute.normalInv}}

-}

-

new file mode 100644

@@ -0,0 +1,32 @@

+\name{compute.fisher}

+\alias{compute.fisher}

+\title{Combine independent p-values using the Fisher method}

+\usage{

+  compute.fisher(p, eps = 1e-06)

+}

+\arguments{

+  \item{p}{a vector of independent p-values}

+

+  \item{eps}{the minimal p-value considered (all p-values

+  smaller will be set to this value)}

+}

+\description{

+  Combine independent p-values using the Fisher method

+}

+\examples{

+p <- c(.1, .01)

+compute.fisher(p)

+}

+\author{

+  Calin Voichita and Sorin Draghici

+}

+\references{

+  Tarca AL., Draghici S., Khatri P., Hassan SS., Kim J.,

+  Kim CJ., Kusanovic JP., Romero R.: "A Signaling Pathway

+  Impact Analysis for Microarray Experiments", 2008,

+  Bioinformatics, 2009, 25(1):75-82.

+}

+\seealso{

+  \code{\link{pe}},\code{\link{compute.normalInv}}

+}

+

@@ -21,7 +21,12 @@ compute.normalInv(p)

 \author{

   Calin Voichita and Sorin Draghici

 }

+\references{

+  Tarca AL., Draghici S., Romero R.: "A Mmore Specific

+  Method To Combine Perturbation and Over-representation

+  Evidence in Pathway Analysis", PSB 2010 poster.

+}

 \seealso{

-  \code{\link{pe}},\code{\link{compute.fischer}}

+  \code{\link{pe}},\code{\link{compute.fisher}}

 }

@@ -16,7 +16,7 @@

   \item{comb.pv.func}{the function to combine the p-values

   - takes as input a vector of p-values and returns the

   combined p-value (default:

-  \code{\link{compute.fischer}}).}

+  \code{\link{compute.fisher}}).}

   \item{adjust.method}{the name of the method to adjust the

   p-value (see \code{\link{p.adjust}})}