@@ -1,10 +1,11 @@

 Package: ROntoTools

 Type: Package

 Title: R Onto-Tools suite

-Version: 1.11.0

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

+Version: 1.99.0

+Author: Calin Voichita <calin@wayne.edu> and Sahar Ansari

+    <saharansari@wayne.edu> and Sorin Draghici <sorin@wayne.edu>

 Maintainer: Calin Voichita <calin@wayne.edu>

-Description: Suite of tools for functional analysis

+Description: Suite of tools for functional analysis.

 biocViews: NetworkAnalysis, Microarray, GraphsAndNetworks

 License: CC BY-NC-ND 4.0 + file LICENSE

 Depends:

@@ -17,15 +18,4 @@ Depends:

 Suggests:

     RUnit,

     BiocGenerics

-Collate:

-    'pathwayExpress.R'

-    'utils.R'

-    'graphWeights.R'

-    'keggDataREST.R'

-    'AllClasses.R'

-    'AllGenerics.R'

-    'nodeWeights-methods.R'

-    'pePathway-utils.R'

-    'Summary-methods.R'

-    'plot-methods.R'

-    'renderInfo-methods.R'

+RoxygenNote: 5.0.1

@@ -1,22 +1,29 @@

+# Generated by roxygen2: do not edit by hand

+

+S3method(summary,pDisRes)

+S3method(summary,peRes)

 export(alpha1MR)

 export(alphaMLG)

 export(compute.fisher)

 export(compute.normalInv)

 export(keggPathwayGraphs)

 export(keggPathwayNames)

+export(nodeWeights)

+export(pDis)

 export(pe)

 export(peEdgeRenderInfo)

 export(peNodeRenderInfo)

 export(setEdgeWeights)

 export(setNodeWeights)

+exportClasses(pDisPathway)

+exportClasses(pDisRes)

 exportClasses(pePathway)

 exportClasses(peRes)

+exportMethods(Summary)

 exportMethods(nodeWeights)

 exportMethods(plot)

-exportMethods(Summary)

-import(boot)

-import(graph)

 import(KEGGREST)

 import(KEGGgraph)

+import(boot)

+import(graph)

 import(parallel)

-importMethodsFrom(KEGGgraph)

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

+VERSION 2.0.0

+--------

+

+* added a novel pathway analysis method based on the primary dis-regulation of the genes in each pathway

+

 VERSION 1.2.0

 --------

@@ -5,13 +5,13 @@

 #' @details

 #' 

 #' The slots \code{input} and \code{ref} record global information related to the whole analysis, 

-#' while the \code{pathways} slot records the specific results as \code{\link{pePathway}} for each one of the pathways used in the analysis.

+#' while the \code{pathways} slot records the specific results as \code{\link{pePathway-class}} for each one of the pathways used in the analysis.

 #' 

 #' 

 #' @section Slots: 

 #' 

 #' \describe{

-#'     \item{\code{pathways}:}{A list of \code{\link{pePathway}} objects.}

+#'     \item{\code{pathways}:}{A list of \code{\link{pePathway-class}} objects.}

 #'     \item{\code{input}:}{named vector of fold changes used for the analysis. The names of the vector are the IDs originaly used.}

 #'     \item{\code{ref}:}{character vector containing the IDs used as reference in the analysis.}

 #'     \item{\code{cutOffFree}:}{boolean value indicating if a cut-of-free analysis has been performed.}

@@ -21,9 +21,8 @@

 #' 

 #' Calin Voichita and Sorin Draghici

 #'

-#' @seealso \code{\link{pe}}, \code{\link{pePathway}}

+#' @seealso \code{\link{pe}}, \code{\link{pePathway-class}}

 #'

-#' @aliases peRes-class

 #' @exportClass peRes

 setClass("peRes",

          representation(pathways = "list",

@@ -45,6 +44,7 @@ setClass("peRes",

 #'    \item{\code{boot}:}{an object of class \code{boot} encoding the bootstrap information.}

 #'    \item{\code{Pert}:}{the gene perturbation factors for all genes on the pathway, as computed by Pathway-Express.}

 #'    \item{\code{Acc}:}{the gene accumulations for all genes on the pathway, as computed by Pathway-Express.}

+#'    \item{\code{asGS}:}{pathway was considered as gene set}

 #' }

 #' 

 #' @author

@@ -52,7 +52,7 @@ setClass("peRes",

 #' Calin Voichita and Sorin Draghici

 #'

 #'             

-#' @seealso \code{\link{pe}}, \code{\link{peRes}}

+#' @seealso \code{\link{pe}}, \code{\link{peRes-class}}

 #' 

 #' @aliases pePathway-class

 #' @import graph

@@ -69,3 +69,75 @@ setClass("pePathway",

          prototype(map = new("graphNEL")

          )

 )

+

+

+#' Primary dis-regulation (pDis) result class

+#' 

+#' This class is used to encode the results of the pathway analysis performed by the function \code{\link{pDis}}.

+#' 

+#' @details

+#' 

+#' The slots \code{input} and \code{ref} record global information related to the whole analysis, 

+#' while the \code{pathways} slot records the specific results as \code{\link{pDisPathway-class}} for each one of the pathways used in the analysis.

+#' 

+#' 

+#' @section Slots: 

+#' 

+#' \describe{

+#'     \item{\code{pathways}:}{A list of \code{\link{pDisPathway-class}} objects.}

+#'     \item{\code{input}:}{named vector of fold changes used for the analysis. The names of the vector are the IDs originaly used.}

+#'     \item{\code{ref}:}{character vector containing the IDs used as reference in the analysis.}

+#'     \item{\code{cutOffFree}:}{boolean value indicating if a cut-of-free analysis has been performed.}

+#'   }

+#' 

+#' @author

+#' 

+#' Calin Voichita, Sahar Ansari and Sorin Draghici

+#'

+#' @seealso \code{\link{pDis}}, \code{\link{pDisPathway-class}}

+#'

+#' @aliases pDisRes-class

+#' @exportClass pDisRes

+setClass("pDisRes",

+         representation(pathways = "list",

+                        input = "numeric",

+                        ref = "character",

+                        cutOffFree = "logical"),

+         prototype(pathways = list(), cutOffFree = FALSE)

+)

+

+#' Class that encodes the result of pDis analysis for a single pathway

+#' 

+#' 

+#' @section Slots:

+#' 

+#' \describe{

+#'    \item{\code{map}:}{an object of type graph (e.g., \code{\link{graphNEL}}).}

+#'    \item{\code{input}:}{named vector of fold changes for genes on this pathway. The names of the genes are the orignal IDS used in the analysis}

+#'    \item{\code{ref}:}{vector of reference IDs on this pathway}

+#'    \item{\code{boot}:}{an object of class \code{boot} encoding the bootstrap information.}

+#'    \item{\code{pDis}:}{the gene primary dis-regulation for all genes on the pathway, as computed by primary dis-regulation.}

+#'    \item{\code{asGS}:}{pathway was considered as gene set}

+#' }

+#' 

+#' @author

+#' 

+#' Calin Voichita, Sahar Ansari and Sorin Draghici

+#'

+#'             

+#' @seealso \code{\link{pDis}}, \code{\link{pDisRes-class}}

+#' 

+#' @aliases pDisPathway-class

+#' @import graph

+#' @exportClass pDisPathway

+setClass("pDisPathway", 

+         representation(map = "graph",

+                        input = "numeric",

+                        ref = "character",

+                        boot = "ANY",

+                        pDis = "numeric",

+                        asGS = "logical"

+         ), 

+         prototype(map = new("graphNEL")

+         )

+)

@@ -1,133 +1,30 @@

+

 #' Summarize the results of a Pathway-Express analysis

 #' 

-#' 

-#' @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.fisher,

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

-#' 

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

-#' @param pathNames named vector of pathway names; the names of the vector are the IDs of the pathways

-#' @param totalAcc boolean value indicating if the total accumulation should be computed

-#' @param totalPert boolean value indicating if the total perturbation should be computed

-#' @param normalize boolean value indicating if normalization with regards to the boostrap simulations should be performed on totalAcc and totalPert

-#' @param pPert boolean value indicating if the significance of the total perturbation in regards to the bootstrap permutations should be computed

-#' @param pAcc boolean value indicating if the significance of the total accumulation in regards to the bootstrap permutations should be computed

-#' @param pORA boolean value indicating if the over-represtation p-value should be computed

-#' @param comb.pv vector of the p-value names to be combine (any of the above p-values)

-#' @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

-#' @param order.by the name of the p-value that is used to order the results

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

-#' 

-#' @seealso \code{\link{pe}}

-#' 

-#' @examples

-#' 

-#' # load experiment

-#' load(system.file("extdata/E-GEOD-21942.topTable.RData", package = "ROntoTools"))

-#' fc <- top$logFC[top$adj.P.Val <= .01]

-#' names(fc) <- top$entrez[top$adj.P.Val <= .01]

-#' ref <- top$entrez

-#' 

-#' # load the set of pathways

-#' kpg <- keggPathwayGraphs("hsa")

-#' kpg <- setEdgeWeights(kpg)

-#' kpg <- setNodeWeights(kpg, defaultWeight = 1)

-#' 

-#' # perform the pathway analysis

-#' peRes <- pe(fc, graphs = kpg, ref = ref, nboot = 100, verbose = TRUE)

-#' 

-#' # obtain summary of results

-#' head(Summary(peRes))

-#' 

-#' kpn <- keggPathwayNames("hsa")

-#' 

-#' head(Summary(peRes))

-#' 

-#' head(Summary(peRes, pathNames = kpn, totalAcc = FALSE, totalPert = FALSE, 

-#'              pAcc = FALSE, pORA = FALSE, comb.pv = NULL, order.by = "pPert"))

-#' 

-#' @rdname Summary-methods

-#' 

-#' @aliases Summary.peRes

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

+#' @param ... see \code{\link{summary.peRes}}

+#' @param na.rm ignored

+#'

 #' @aliases Summary,peRes-method

+#'

 #' @export

 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.fisher,

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

-          {  

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

-              if(test) return(trueCase)

-              else return(falseCase)

-            }

-            

-            pathStats <- function(pePath)

-            {

-              pStats <- 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, 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, 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])), 

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

-              

-              return(unlist(pStats))

-            }

-            

-            if (pORA & x@cutOffFree)

-            {

-              pORA <- FALSE

-              if ("pORA" %in% comb.pv)

-              {

-                order.by <- setdiff(comb.pv, "pORA")[1]

-                comb.pv <- NULL

-              }

-              message("The over-representaion p-value is not defined for cut-off free analysis and will not be computed!")  

-            }

-            

-            if(!is.null(comb.pv))

-            {

-              if(!all(comb.pv %in% c("pPert","pAcc","pORA")))

-              {

-                warning("The p-value to be combined are not specified correctly. No combination p-value will be calculated!")

-                comb.pv <- NULL

-                if(order.by == "pComb")

-                  order.by <- NULL

-              }else{

-                for(i in 1:length(comb.pv))

-                  assign(comb.pv[i], TRUE)

-              }

-            }

-            

-            topStats <- data.frame(do.call(rbind, lapply(x@pathways, pathStats)))

-            

-            if(!is.null(pathNames))

-            {

-              pathNames <- pathNames[rownames(topStats)]

-              topStats <- cbind(pathNames, topStats)

-            }

-            

-            if(order.by %in% colnames(topStats))

-            {

-              topStats <- topStats[order(topStats[,order.by]),]

-            }

-            

-            allPVs <- c("pPert","pAcc","pORA", "pComb")

-            

-            lapply(allPVs[allPVs %in% colnames(topStats)],

-                   function(pv)

-                     topStats[[paste(pv, "." , adjust.method, sep = "")]] <<- p.adjust(topStats[[pv]], adjust.method)

-            )

-            return(topStats)

-          }

-)

\ No newline at end of file

+  function(x, ..., na.rm = FALSE) {

+    return(summary.peRes(x, ...));

+  }

+)

+

+#' Summarize the results of a Pathway-Express analysis

+#' 

+#' @param x Primary dis-regulation analysis result object obtained using \code{\link{pDis}}

+#' @param ... see \code{\link{summary.pDisRes}}

+#' @param na.rm ignored

+#'

+#' @aliases Summary,pDisRes-method

+#'

+#' @export

+setMethod("Summary", c("x" = "pDisRes"),

+  function(x, ..., na.rm = FALSE) {

+    return(summary.pDisRes(x, ...));

+  }

+)

@@ -82,7 +82,6 @@ loadKEGGpathwayDataREST <- function(organism = "hsa",

 #' head(nodes(kpg[["path:hsa04110"]]))

 #' head(edges(kpg[["path:hsa04110"]]))

 #' 

-#' @importMethodsFrom KEGGgraph

 #' @export

 keggPathwayGraphs <- function(organism = "hsa", 

                               targRelTypes = c("GErel","PCrel","PPrel"),

new file mode 100644

@@ -0,0 +1,254 @@

+#' Primary dis-regulation: Pathway analysis approach based on the unexplained dis-regulation of genes 

+#' 

+#' 

+#' @param x named vector of log fold changes for the differentially expressed genes; \code{names(x)} must use the same id's as \code{ref} and the nodes of the \code{graphs}

+#' @param graphs list of pathway graphs as objects of type \code{graph} (e.g., \code{\link{graphNEL}}); the graphs must be weighted graphs (i.e., have an attribute \code{weight} for both nodes and edges)

+#' @param ref the reference vector for all genes in the analysis; if the reference is not provided or it is identical to \code{names(x)} a cut-off free analysis is performed

+#' @param nboot number of bootstrap iterations

+#' @param verbose print progress output

+#' @param cluster a cluster object created by makeCluster for parallel computations

+#' @param seed an integer value passed to set.seed() during the boostrap permutations

+#' 

+#' @details

+#' 

+#' See details in the cited articles.

+#' 

+#' @return

+#' 

+#' An object of class \code{\link{pDisRes-class}}.

+#' 

+#' @author

+#' 

+#' Calin Voichita, Sahar Ansari and Sorin Draghici

+#' 

+#' @references

+#' 

+#' Voichita C., Donato M., Draghici S.: "Incorporating gene significance in the impact analysis of signaling pathways", IEEE Machine Learning and Applications (ICMLA), 2012 11th International Conference on, Vol. 1, p.126-131, 2012

+#' Ansari, S., Voichita, C., Donato, M., Tagett, R., & Draghici, S. A Novel Pathway Analysis Approach Based on the Unexplained Disregulation of Genes.

+#' 

+#' 

+#' @seealso \code{\link{Summary}}, 

+#' \code{\link{keggPathwayGraphs}}, \code{\link{setNodeWeights}}, \code{\link{setEdgeWeights}}

+#' 

+#' @examples

+#' 

+#' # load a multiple sclerosis study (public data available in Array Express 

+#' # ID: E-GEOD-21942)

+#' # This file contains the top table, produced by the limma package with 

+#' # added gene information. All the probe sets with no gene associate to them,

+#' # have been removed. Only the most significant probe set for each gene has been

+#' # kept (the table is already ordered by p-value)

+#' # The table contains the expression fold change and signficance of each  

+#' # probe set in peripheral blood mononuclear cells (PBMC) from 12 MS patients

+#' # and 15 controls.

+#' load(system.file("extdata/E-GEOD-21942.topTable.RData", package = "ROntoTools"))

+#' head(top)

+#' 

+#' # select differentially expressed genes at 1% and save their fold change in a 

+#' # vector fc and their p-values in a vector pv

+#' fc <- top$logFC[top$adj.P.Val <= .01]

+#' names(fc) <- top$entrez[top$adj.P.Val <= .01]

+#' 

+#' pv <- top$P.Value[top$adj.P.Val <= .01]

+#' names(pv) <- top$entrez[top$adj.P.Val <= .01]

+#' 

+#' # alternativly use all the genes for the analysis

+#' # NOT RUN: 

+#' # fc <- top$logFC

+#' # names(fc) <- top$entrez

+#' 

+#' # pv <- top$P.Value

+#' # names(pv) <- top$entrez

+#' 

+#' # get the reference

+#' ref <- top$entrez

+#' 

+#' # load the set of pathways

+#' kpg <- keggPathwayGraphs("hsa")

+#' 

+#' # set the beta information (see the citated documents for meaning of beta)

+#' kpg <- setEdgeWeights(kpg)

+#' 

+#' # inlcude the significance information in the analysis (see Voichita:2012 

+#' # for more information)

+#' # set the alpha information based on the pv with one of the predefined methods

+#' kpg <- setNodeWeights(kpg, weights = alphaMLG(pv), defaultWeight = 1)

+#' 

+#' # perform the pathway analysis

+#' # in order to obtain accurate results the number of boostraps, nboot, should 

+#' # be increase to a number like 2000

+#' pDisRes <- pDis(fc, graphs = kpg, ref = ref, nboot = 100, verbose = TRUE)

+#' 

+#' # obtain summary of results

+#' head(Summary(pDisRes))

+#' 

+#' @export

+pDis <- function(x, graphs, ref = NULL, nboot = 2000, verbose = TRUE, cluster = NULL, seed = NULL)

+{

+  cutOffFree <- FALSE

+  if (is.null(ref))

+  {

+    ref <- names(x)

+    cutOffFree <- TRUE

+  }

+  else

+  {

+    if (!any(is.na(match(ref,names(x)))))

+    {

+      warning("All the reference IDs are part of the input. Cut-off free analysis is performed.") 

+      ref <- names(x)

+      cutOffFree <- TRUE

+    }

+  }

+  

+  preservedSeed <- NULL

+  if (exists(".Random.seed"))

+    preservedSeed <- .Random.seed

+  

+  if(!is.null(seed))

+    set.seed(seed)

+  

+  if (any(is.na(match(names(x), ref))))

+  {

+    warning("There are input IDs not available in the reference. These will be excluded from analysis.")

+    x <- x[!is.na(match(names(x), ref))]

+  }

+  

+  pDisRes <- pDis.helper(x = x, ref = ref, graphs = graphs, nboot = nboot, verbose = verbose, cluster = cluster, seed = seed)

+  pDisRes@cutOffFree <- cutOffFree

+  

+  if(is.null(preservedSeed))

+  {

+    if(!is.null(seed))

+      rm(.Random.seed)

+  }

+  else

+    .Random.seed <- preservedSeed

+  

+  return(pDisRes)

+}

+

+#' @import parallel

+pDis.helper <- function(x, graphs, ref = NULL, nboot = 2000, verbose = TRUE, cluster = NULL, seed = NULL)

+{

+  if(verbose)

+  {

+    message("Performing pathway analysis...")

+    if(is.null(cluster))

+    {

+      pb <- txtProgressBar(min = 0, max = length(graphs), style = 3)  

+    }

+  }

+  

+  t1 <- Sys.time()

+  if (is.null(cluster))

+  {

+    allBoot <- lapply(graphs, function(g, seed) {

+      if(!is.null(seed))

+        set.seed(seed)

+      ret <- pDis.boot(g, x = x, ref = ref, nboot = nboot)

+      if(verbose)

+        setTxtProgressBar(pb, getTxtProgressBar(pb) + 1)

+      return(ret)

+    }, seed = seed)

+  }

+  else

+  {

+    clusterExport(cluster, c("pDis.boot", "compute.inverse", "compute.B_pDis"))

+    clusterEvalQ(cluster, library(ROntoTools))

+    

+    allBoot <- parLapply(cluster, graphs, function(g, seed) {

+      if(!is.null(seed))

+        set.seed(seed)

+      ret <- pDis.boot(g, x = x, ref = ref, nboot = nboot)

+      return(ret)

+    }, seed = seed)

+    

+  }

+  t2 <- Sys.time()

+  

+  if(verbose)

+  {

+    message("Analysis completed in ", format(t2-t1), ".")

+  }

+  

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

+  

+  pDisRes <- new("pDisRes", pathways = allBoot, input = x, ref = ref)

+  

+  return(pDisRes)

+}

+

+#' @import boot

+#' @keywords internal

+pDis.boot <- function(g, x, ref, nboot, all.genes = F)

+{

+  inv <- (compute.B_pDis(g))

+  

+  pDisPath <- new("pDisPathway", 

+                map = g, 

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

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

+  

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

+    return(NULL)

+  

+  if (is.null(inv))

+  {

+    pDisPath@asGS <- TRUE

+    return(pDisPath)

+  }

+  

+  # 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)  {

+    y <- sample(l$fc, length(x))

+    names(y) <- sample(l$ref, length(x))

+    return(y)

+  }

+  

+  pDisPath@boot <- boot(pDisPath@input, 

+                      function(x, inv) {

+                        xx <- rep(0, nrow(inv));  names(xx) <- rownames(inv);

+                        xx[names(x)] <- x

+                        xx <- xx * nodeWeights(pDisPath@map, names(xx))

+                        tt = inv %*% xx;

+                        ret <- c(sum(abs(tt)))

+                        names(ret) <- c("tpDis")

+                        return(ret)

+                      }, 

+                      nboot,

+                      "parametric", ran.gen = ran.gen.de, mle = list(ref = pDisPath@ref, fc = as.numeric(x)),

+                      inv = inv

+  )

+  colnames(pDisPath@boot$t) <- names(pDisPath@boot$t0)

+  

+  xx <- rep(0, nrow(inv))

+  names(xx) <- rownames(inv)

+  xx[names(pDisPath@input)] <- pDisPath@input  

+  pDisPath@pDis = (inv %*% xx)[,1];

+  pDisPath@asGS <- FALSE

+  

+  return(pDisPath) 

+}

+

+

+compute.B_pDis <- function(g, non.zero = TRUE)

+{

+  if (non.zero)

+    # number of downstream genes (like in SPIA)

+    nds <- sapply(edgeWeights(g), function(x) sum(x != 0 ))

+  else

+    nds <- sapply(edges(g), length)

+  

+  # add 1 for all genes that do not have downstream genes to avoid division by 0

+  # this does not affect the computation

+  nds[nds == 0] <- 1

+  

+  # compute B = (I - beta/nds)

+  #B <- t(diag(length(nodes(g))) - as(g, "matrix") / nds)

+  #

+  B <- diag(length(nodes(g))) - t(as(g, "matrix")) / matrix(nds, byrow=TRUE, nrow = length(nds), ncol = length(nds))

+   return(B)

+}

+ 

new file mode 100644

@@ -0,0 +1,23 @@

+

+compute.ppDis <- function(pDisPath)

+  ifelse( !all(pDisPath@boot$t[,"tpDis"] == 0),

+          compute.bootPV(pDisPath@boot$t0["tpDis"], pDisPath@boot$t[,"tpDis"]),

+          NA)

+

+

+compute.pORA <- function(pDisPath, inputSize, refSize)

+  phyper(q = length(pDisPath@input)-1,

+         m = length(pDisPath@ref),

+         n = refSize-length(pDisPath@ref),

+         k = inputSize,

+         lower.tail = FALSE) 

+

+

+get.totalpDis <- function(pDisPath)

+  as.numeric(pDisPath@boot$t0["tpDis"])

+

+get.totalpDisNorm <- function(pDisPath)

+  ifelse( !all(pDisPath@boot$t[,"tpDis"] == 0),

+          as.numeric((pDisPath@boot$t0["tpDis"] - mean(pDisPath@boot$t[,"tpDis"])) / sd(pDisPath@boot$t[,"tpDis"])),

+          NA)

+

@@ -15,7 +15,7 @@

 #' 

 #' @return

 #' 

-#' An object of class \code{\link{peRes}}.

+#' An object of class \code{\link{peRes-class}}.

 #' 

 #' @author

 #' 

@@ -31,7 +31,7 @@

 #' 

 #' Draghici S., Khatri P., Tarca A.L., Amin K., Done A., Voichita C., Georgescu C., Romero R.: "A systems biology approach for pathway level analysis". Genome Research, 17, 2007. 

 #' 

-#' @seealso \code{\link{Summary}}, \code{\link{plot.peRes}}, 

+#' @seealso \code{\link{Summary}}, \code{\link{plot,peRes,missing-method}}, 

 #' \code{\link{keggPathwayGraphs}}, \code{\link{setNodeWeights}}, \code{\link{setEdgeWeights}}

 #' 

 #' @examples

@@ -1,19 +1,3 @@

-# setMethod("plot", signature(x="pePathway", y="ANY"),

-#           function(x, y, ...){

-#             

-#             nShape <- rep("circle", length(nodes(x@map)))

-#             names(nShape) <- nodes(x@map)

-#             nShape[names(x@input)] <- "box"

-#             

-#             m <- as(x@map, "matrix")

-#             nodeToPlot <- nodes(x@map)[(colSums(abs(m)) != 0) & (rowSums(abs(m)) != 0)]

-#             

-#             plot(x@map,  nodeAttrs = list(

-#               fillcolor = pf2col(x@PF), 

-#               fontsize = addNames(340.0, nodes(x@map)),

-#               shape = nShape

-#               ))

-#           })

 compute.pAcc <- function(pePath)

   ifelse( !all(pePath@boot$t[,"tAcc"] == 0),

@@ -6,15 +6,16 @@

 #' statistics of the same factors.

 #' 

 #' 

-#' @param x an object of type \code{\link{pePathway}}

-#' @param y if provided, the factor to be ploted (either \code{Acc} (default) or \code{Pert}; see \code{\link{pePathway}})

+#' @param x an object of type \code{\link{pePathway-class}}

+#' @param y if provided, the factor to be ploted (either \code{Acc} (default) or \code{Pert}; see \code{\link{pePathway-class}})

+#' @param main title

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

 #' @param type type of plot (either \code{two.way} (default) or \code{boot})

 #' @param eps any value smaller than this will be ploted as 0

 #' 

 #' @author Calin Voichita and Sorin Draghici

 #' 

-#' @seealso \code{\link{pe}}, \code{\link{plot.peRes}}, \code{\link{peNodeRenderInfo}}, \code{\link{peEdgeRenderInfo}}

+#' @seealso \code{\link{pe}}, \code{\link{plot,peRes,missing-method}}, \code{\link{peNodeRenderInfo}}, \code{\link{peEdgeRenderInfo}}

 #' 

 #' @examples

 #' 

@@ -41,10 +42,7 @@

 #' plot(peRes@@pathways[[50]], "Pert", type = "boot", main = "Perturbation factor")

 #' 

 #' @rdname plot.pePathway-methods

-#' @name plot.pePathway

 #' 

-#' @aliases plot.pePathway

-#' @aliases plot,pePathway,missing-method

 #' @export

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

           function(x, y, ..., type = "two.way", eps = 1e-6)

@@ -55,8 +53,6 @@ setMethod("plot", signature(x="pePathway", y="missing"),

 #' @rdname plot.pePathway-methods

 #' 

-#' @aliases plot.pePathway

-#' @aliases plot,pePathway,character-method

 #' @export

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

           function(x, y, main = "", ... , type = "two.way", eps = 1e-6)

@@ -110,7 +106,7 @@ setMethod("plot", signature(x="pePathway", y="character"),

 #' 

 #' @description Display a two-way plot using two of the p-values from the Pathway-Express analysis.

 #' 

-#' @param x an object of type \code{\link{peRes}}

+#' @param x an object of type \code{\link{peRes-class}}

 #' @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 

@@ -121,7 +117,7 @@ setMethod("plot", signature(x="pePathway", y="character"),

 #' 

 #' @author Calin Voichita and Sorin Draghici

 #' 

-#' @seealso \code{\link{pe}}, \code{\link{Summary.peRes}}, \code{\link{plot.pePathway}}

+#' @seealso \code{\link{pe}}, \code{\link{summary.peRes}}, \code{\link{plot,pePathway,missing-method}}

 #' 

 #' @examples

 #' 

@@ -144,10 +140,7 @@ setMethod("plot", signature(x="pePathway", y="character"),

 #' plot(peRes, c("pPert","pORA"), comb.pv.func = compute.normalInv, threshold = .01)

 #' 

 #' @rdname plot.peRes-methods

-#' @name plot.peRes

 #' 

-#' @aliases plot.peRes

-#' @aliases plot,peRes,missing-method

 #' @export

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

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

@@ -158,9 +151,7 @@ setMethod("plot", signature(x="peRes", y="missing"),

 )

 #' @rdname plot.peRes-methods

-#' 

-#' @aliases plot.peRes

-#' @aliases plot,peRes,character-method

+#'

 #' @export

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

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

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

-#' Extract edge render information from a \code{pePathway} object

+#' Extract edge render information from a \code{pePathway-class} object

 #' 

-#' @param x an object of class \code{\link{pePathway}}

+#' @param x an object of class \code{\link{pePathway-class}}

 #' @param pos.col color of the edges with possitive weight

 #' @param pos.lty line type of the edges with possitive weight

 #' @param pos.ah arrow head of the edges with possitive weight 

@@ -11,7 +11,7 @@

 #' @param zero.lty color of the edges with zero weight

 #' @param zero.ah color of the edges with zero weight

 #' 

-#' @value a named list as expected by \code{\link{edgeRenderInfo}}

+#' @return a named list as expected by \code{\link{edgeRenderInfo}}

 #' 

 #' @author Calin Voichita and Sorin Draghici

 #' 

@@ -76,17 +76,17 @@ peEdgeRenderInfo <- function(x,

   ))

 }

-#' Extract node render information from a \code{pePathway} object

+#' Extract node render information from a \code{pePathway-class} object

 #' 

-#' @param x an object of class \code{\link{pePathway}}

-#' @param y a string representing the factor to be represented (\code{Pert, Acc} or \code{input}; see \code{\link{pePathway}})

+#' @param x an object of class \code{\link{pePathway-class}}

+#' @param y a string representing the factor to be represented (\code{Pert, Acc} or \code{input}; see \code{\link{pePathway-class}})

 #' @param input.shape shape of nodes that have measured expression change

 #' @param default.shape shape of all other nodes

 #' @param pos.col color of nodes with a positive \code{y} factor

 #' @param neg.col color of nodes with a negative \code{y} factor

 #' @param zero.col color of nodes with the \code{y} factor equal to zero

 #' 

-#' @value a named list as expected by \code{\link{nodeRenderInfo}}

+#' @return a named list as expected by \code{\link{nodeRenderInfo}}

 #' 

 #' @author Calin Voichita and Sorin Draghici

 #' 

new file mode 100644

@@ -0,0 +1,123 @@

+#' Summarize the results of a primary dis-regulation (pDis) analysis

+#' 

+#' @usage summary.pDisRes(object, ..., pathNames = NULL, totalpDis = TRUE, normalize = TRUE, 

+#'  ppDis = TRUE, pORA = TRUE, 

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

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

+#' 

+#' @param object pDis analysis result object obtained using \code{\link{pDis}}

+#' @param ... ignored

+#' @param pathNames named vector of pathway names; the names of the vector are the IDs of the pathways

+#' @param totalpDis boolean value indicating if the total primary dis-regulation should be computed

+#' @param normalize boolean value indicating if normalization with regards to the boostrap simulations should be performed on totalpDis

+#' @param ppDis boolean value indicating if the significance of the total primary dis-regulation in regards to the bootstrap permutations should be computed

+#' @param pORA boolean value indicating if the over-represtation p-value should be computed

+#' @param comb.pv vector of the p-value names to be combine (any of the above p-values)

+#' @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

+#' @param order.by the name of the p-value that is used to order the results

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

+#' 

+#' @seealso \code{\link{pDis}}

+#' 

+#' @examples

+#' 

+#' # load experiment

+#' load(system.file("extdata/E-GEOD-21942.topTable.RData", package = "ROntoTools"))

+#' fc <- top$logFC[top$adj.P.Val <= .01]

+#' names(fc) <- top$entrez[top$adj.P.Val <= .01]

+#' ref <- top$entrez

+#' 

+#' # load the set of pathways

+#' kpg <- keggPathwayGraphs("hsa")

+#' kpg <- setEdgeWeights(kpg)

+#' kpg <- setNodeWeights(kpg, defaultWeight = 1)

+#' 

+#' # perform the pathway analysis

+#' pDisRes <- pDis(fc, graphs = kpg, ref = ref, nboot = 100, verbose = TRUE)

+#' 

+#' # obtain summary of results

+#' head(summary(pDisRes))

+#' 

+#' kpn <- keggPathwayNames("hsa")

+#' 

+#' head(summary(pDisRes))

+#' 

+#' head(summary(pDisRes, pathNames = kpn, totalpDis = FALSE, 

+#'             pORA = FALSE, comb.pv = NULL, order.by = "pDis"))

+#' 

+#' @export

+summary.pDisRes <- function(object, ..., pathNames = NULL, totalpDis = TRUE, normalize = TRUE, 

+                   ppDis = TRUE, pORA = TRUE, 

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

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

+{  

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

+    if(test) return(trueCase)