@@ -12,7 +12,7 @@ Description: Pathway Expression Profiles (PEPs) are based on the

     perturbagens.

 License: GPL-3

 Imports:

-    repo,

+    repo (>= 2.1.1),

     XML,

     foreach,

     stats,

@@ -22,7 +22,7 @@ Suggests:

     testthat,

     knitr,

     rmarkdown

-RoxygenNote: 5.0.1

+RoxygenNote: 6.0.1

 VignetteBuilder: knitr

 biocViews: GeneExpression,

     DifferentialExpression,

@@ -10,26 +10,35 @@

 #' @details

 #'

 #' \code{gep2pep} creates a local repository of gene sets, which can

-#' also be imported from the MSigDB database. The local repository is

-#' in the \code{repo} format. When a GEP, defined as a ranked list of

-#' genes, is passed to \code{\link{buildPEPs}}, the stored database of

-#' pathways is used to convert the GEP to a PEP and permanently store

-#' the latter.

+#' also be imported from the MSigDB [1] database. The local repository

+#' is in the \code{repo} format. When a GEP, defined as a ranked list

+#' of genes, is passed to \code{\link{buildPEPs}}, the stored database

+#' of pathways is used to convert the GEP to a PEP and permanently

+#' store the latter.

 #'

 #' One type of analysis that can be performed on PEPs and that is

 #' directly supported by \code{gep2pep} is the Drug-Set Enrichment

-#' Analysis (DSEA, see reference section). It finds pathways that

-#' are consistently dysregulated by a set of drugs, as opposed to a

-#' background of other drugs. Of course PEPs may refer to

-#' non-pharmacological perturbagens (genetic perturbations, disease

-#' states, etc.) for analogous analyses. See \code{\link{PertSEA}}

-#' function.

+#' Analysis (DSEA [2]). It finds pathways that are consistently

+#' dysregulated by a set of drugs, as opposed to a background of other

+#' drugs. Of course PEPs may refer to non-pharmacological perturbagens

+#' (genetic perturbations, disease states, etc.) for analogous

+#' analyses. See \code{\link{PertSEA}} function.

 #'

 #' A complementary approach is that of finding perturbagens that

 #' consistently dysregulate a set of pathways. This is the

 #' pathway-based version of the Gene Set Enrichment Analysis

-#' (GSEA). See \code{\link{PathSEA}}.

-#'

+#' (GSEA). As an application example, this approach can be used to

+#' find drugs mimicking the dysregulation of a gene by looking for

+#' drugs dysregulating pathways involving the gene (this has been

+#' published as the \code{gene2drug} tool [3]). See

+#' \code{\link{PathSEA}}.

+#'

+#' Both DSEA and gene2drug analyses can be performed using

+#' preprocessed data from

+#' \url{http://dsea.tigem.it/downloads.php}. The data include

+#' Connectivity Map GEPs converted to PEPs in the form of a

+#' \code{gep2pep} repository.

+#' 

 #' Naming conventions:

 #'

 #' \itemize{

@@ -60,10 +69,20 @@

 #'   package. It is implemented in \code{repo} format.}

 #'

 #' }

-#' @references Napolitano F. et al, Drug-set enrichment analysis: a

-#'     novel tool to investigate drug mode of action. Bioinformatics

-#'     32, 235-241 (2016).

-#' 

+#' @references 

+#'

+#' [1] Subramanian A. et al. Gene set enrichment analysis: A

+#'     knowledge-based approach for interpreting genome-wide

+#'     expression profiles. PNAS 102, 15545–15550 (2005).

+#'

+#' [2] Napolitano F. et al, Drug-set enrichment analysis: a novel tool

+#'     to investigate drug mode of action. Bioinformatics 32, 235-241

+#'     (2016).

+#'

+#' [3] Napolitano F. et al, gene2drug: a Computational Tool for

+#'     Pathway-based Rational Drug Repositioning, bioRxiv 192005; doi:

+#'     https://doi.org/10.1101/192005

+#'

 #' @docType package

 #' @name gep2pep-package

 #' @author Francesco Napolitano \email{franapoli@@gmail.com}

@@ -189,6 +208,7 @@ importMSigDB.xml <- function(fname) {

 #' Check both repository data consistency (see \code{repo_check} from

 #' the \code{repo} package) and specific gep2pep data consistency.

 #' @inheritParams dummyFunction

+#' @return Nothing.

 #' @examples

 #' db <- readRDS(system.file("testgmd.RDS", package="gep2pep"))

 #' repo_path <- file.path(tempdir(), "gep2pepTemp")

@@ -216,17 +236,17 @@ checkRepository <- function(rp) {

     off <- setdiff(names(perts), dbs)

     if(length(off>0)) {

-        say("The following collections are in perturbagens",

-            "list but not in repository collections:", "warning",

-            off)

+        say(paste("The following collections are in perturbagens",

+                  "list but not in repository collections:"),

+            "warning", off)

         problems <- TRUE

     }

     off <- setdiff(names(perts), dbs)

     if(length(off>0)) {

-        say("The following collections are in repository",

-            "collections but not in perturbagens list:", "warning",

-            off)

+        say(paste("The following collections are in repository",

+                  "collections but not in perturbagens list:"),

+            "warning", off)

         problems <- TRUE

     }

@@ -235,9 +255,9 @@ checkRepository <- function(rp) {

     off <- setdiff(pepitems, dbs)

     if(length(off>0)) {

-        say("The following collections have PEPs but not",

-            "pathways in the repository:", "warning",

-            off)

+        say(paste("The following collections have PEPs but not",

+                  "pathways in the repository:"),

+                  "warning", off)

         problems <- TRUE

     }

@@ -255,9 +275,9 @@ checkRepository <- function(rp) {

                 peps <- rp$get(dbs[i])

                 if(!identical(colnames(peps$ES), perts[[dbs[i]]])) {

-                    say(paste("Column names in the PEP matrix differ from those",

-                              "in the perturbagens repository item: this is a",

-                              "serious inconsistency!"),

+                    say(paste("Column names in the PEP matrix differ from",

+                              "those in the perturbagens repository item:",

+                              "this is a serious inconsistency!"),

                         "warning")

                     problems <- TRUE

                 }

@@ -897,7 +917,7 @@ PathSEA <- function(rp_peps, pathways, bgsets="all", collections="all",

     pathways <- pwList2pwStruct(pathways)

     for(i in 1:length(pathways))

-        if(!rp$has(names(pathways)[i]))

+        if(!rp_peps$has(names(pathways)[i]))

             say("Cold not find PEPs: ", "error", names(pathways)[i])

     if(length(bgsets)==1 && bgsets != "all") {

@@ -911,10 +931,10 @@ PathSEA <- function(rp_peps, pathways, bgsets="all", collections="all",

             say(paste("There is at least one selected collections for which",

                       "no pathway has been provided"), "warning")

-        offcolls <- setdiff(collections, getCollections(rp_peps))

+        offcols <- setdiff(collections, getCollections(rp_peps))

         if(length(offcols) > 0)

             say("The following collections are not in the repository:",

-                "error", offcolls)

+                "error", offcols)

     }

     collections <- intersect(names(pathways),

@@ -1095,8 +1115,8 @@ storePEPs <- function(rp, db_id, peps) {

         curmat[["PV"]][, oldpeps] <- peps$PV[, oldpeps]

         ## adding new PEPs

-        peps$ES <- cbind(curmat$ES, peps$ES[, newpeps, drop=F])

-        peps$PV <- cbind(curmat$PV, peps$PV[, newpeps, drop=F])

+        peps$ES <- cbind(curmat$ES, peps$ES[, newpeps, drop=FALSE])

+        peps$PV <- cbind(curmat$PV, peps$PV[, newpeps, drop=FALSE])

     }

@@ -1315,6 +1335,6 @@ checkSets <- function(rp, sets) {

         off <- setdiff(sub, names(coll))

         if(length(off) > 0)

             say(paste0("The following pathways could not be found ",

-                      "in collection ", ucoll_ids[i], ": "), "error", off)            

+                      "in collection ", ucoll_ids[i], ": "), "error", off)

     }            

 }

@@ -88,4 +88,3 @@ psea$PathSEA$C3_TFT

 unlink(repo_path, TRUE)

 }

-

@@ -99,4 +99,3 @@ Napolitano F. et al, Drug-set enrichment analysis: a

     novel tool to investigate drug mode of action. Bioinformatics

     32, 235-241 (2016).

 }

-

@@ -85,4 +85,3 @@ unlink(repo_path, TRUE)

 \seealso{

 buildPEPs

 }

-

@@ -79,4 +79,3 @@ unlink(repo_path, TRUE)

 \seealso{

 buildPEPs

 }

-

@@ -23,4 +23,3 @@ Nothing

 \description{

 Dummy function for parameter inheritance

 }

-

@@ -42,4 +42,3 @@ unlink(repo_path, TRUE)

 \seealso{

 PertSEA, PathSEA

 }

-

@@ -38,4 +38,3 @@ unlink(repo_path, TRUE)

 \seealso{

 createRepository, PathSEA

 }

-

@@ -2,8 +2,8 @@

 % Please edit documentation in R/gep2pep.R

 \docType{package}

 \name{gep2pep-package}

-\alias{gep2pep}

 \alias{gep2pep-package}

+\alias{gep2pep}

 \title{gep2pep: creation and analysis of Pathway Expression Profiles}

 \description{

 Pathway Expression Profiles (PEPs) are based on the collective

@@ -14,25 +14,34 @@ and performs enrichment analysis of pathways or perturbagens.

 }

 \details{

 \code{gep2pep} creates a local repository of gene sets, which can

-also be imported from the MSigDB database. The local repository is

-in the \code{repo} format. When a GEP, defined as a ranked list of

-genes, is passed to \code{\link{buildPEPs}}, the stored database of

-pathways is used to convert the GEP to a PEP and permanently store

-the latter.

+also be imported from the MSigDB [1] database. The local repository

+is in the \code{repo} format. When a GEP, defined as a ranked list

+of genes, is passed to \code{\link{buildPEPs}}, the stored database

+of pathways is used to convert the GEP to a PEP and permanently

+store the latter.

 One type of analysis that can be performed on PEPs and that is

 directly supported by \code{gep2pep} is the Drug-Set Enrichment

-Analysis (DSEA, see reference section). It finds pathways that

-are consistently dysregulated by a set of drugs, as opposed to a

-background of other drugs. Of course PEPs may refer to

-non-pharmacological perturbagens (genetic perturbations, disease

-states, etc.) for analogous analyses. See \code{\link{PertSEA}}

-function.

+Analysis (DSEA [2]). It finds pathways that are consistently

+dysregulated by a set of drugs, as opposed to a background of other

+drugs. Of course PEPs may refer to non-pharmacological perturbagens

+(genetic perturbations, disease states, etc.) for analogous

+analyses. See \code{\link{PertSEA}} function.

 A complementary approach is that of finding perturbagens that

 consistently dysregulate a set of pathways. This is the

 pathway-based version of the Gene Set Enrichment Analysis

-(GSEA). See \code{\link{PathSEA}}.

+(GSEA). As an application example, this approach can be used to

+find drugs mimicking the dysregulation of a gene by looking for

+drugs dysregulating pathways involving the gene (this has been

+published as the \code{gene2drug} tool [3]). See

+\code{\link{PathSEA}}.

+

+Both DSEA and gene2drug analyses can be performed using

+preprocessed data from

+\url{http://dsea.tigem.it/downloads.php}. The data include

+Connectivity Map GEPs converted to PEPs in the form of a

+\code{gep2pep} repository.

 Naming conventions:

@@ -65,12 +74,19 @@ Naming conventions:

 }

 }

+\references{

+[1] Subramanian A. et al. Gene set enrichment analysis: A

+    knowledge-based approach for interpreting genome-wide

+    expression profiles. PNAS 102, 15545–15550 (2005).

+

+[2] Napolitano F. et al, Drug-set enrichment analysis: a novel tool

+    to investigate drug mode of action. Bioinformatics 32, 235-241

+    (2016).

+

+[3] Napolitano F. et al, gene2drug: a Computational Tool for

+    Pathway-based Rational Drug Repositioning, bioRxiv 192005; doi:

+    https://doi.org/10.1101/192005

+}

 \author{

 Francesco Napolitano \email{franapoli@gmail.com}

 }

-\references{

-Napolitano F. et al, Drug-set enrichment analysis: a

-    novel tool to investigate drug mode of action. Bioinformatics

-    32, 235-241 (2016).

-}

-

@@ -42,4 +42,3 @@ getCollections(rp)

 unlink(repo_path, TRUE)

 }

-

@@ -69,4 +69,3 @@ str(db_sample[[1]], nchar.max=20)

 \references{

 \url{http://software.broadinstitute.org/gsea/downloads.jsp}

 }

-

@@ -35,4 +35,3 @@ length(db)

 \seealso{

 importMSigDB.xml

 }

-

@@ -42,4 +42,3 @@ unlink(repo_path, TRUE)

 \seealso{

 createRepository

 }

-