Package 'GSA'

Title: Gene Set Analysis
Description: Gene Set Analysis.
Authors: Brad Efron and R. Tibshirani
Maintainer: Rob Tibshirani <[email protected]>
License: LGPL
Version: 1.03.3
Built: 2024-08-19 06:27:13 UTC
Source: CRAN

Help Index


Gene set analysis

Description

Determines the significance of pre-defined sets of genes with respect to an outcome variable, such as a group indicator, a quantitative variable or a survival time

Usage

GSA(x,y, genesets, genenames,
method=c("maxmean","mean","absmean"),
resp.type=c("Quantitative","Two class unpaired","Survival","Multiclass",
            "Two class paired", "tCorr", "taCorr"),
censoring.status=NULL,random.seed=NULL,  knn.neighbors=10,
s0=NULL, s0.perc=NULL,minsize=15,maxsize=500,
restand=TRUE,restand.basis=c("catalog","data"),
 nperms=200, 
xl.mode=c("regular","firsttime","next20","lasttime"), 
xl.time=NULL, xl.prevfit=NULL)

Arguments

x

Data x: p by n matrix of features (expression values), one observation per column (missing values allowed); y: n-vector of outcome measurements

y

Vector of response values: 1,2 for two class problem, or 1,2,3 ... for multiclass problem, or real numbers for quantitative or survival problems

genesets

Gene set collection (a list)

genenames

Vector of genenames in expression dataset

method

Method for summarizing a gene set: "maxmean" (default), "mean" or "absmean"

resp.type

Problem type: "quantitative" for a continuous parameter; "Two class unpaired" ; "Survival" for censored survival outcome; "Multiclass" : more than 2 groups, coded 1,2,3...; "Two class paired" for paired outcomes, coded -1,1 (first pair), -2,2 (second pair), etc

censoring.status

Vector of censoring status values for survival problems, 1 mean death or failure, 0 means censored

random.seed

Optional initial seed for random number generator (integer)

knn.neighbors

Number of nearest neighbors to use for imputation of missing features values

s0

Exchangeability factor for denominator of test statistic; Default is automatic choice

s0.perc

Percentile of standard deviation values to use for s0; default is automatic choice; -1 means s0=0 (different from s0.perc=0, meaning s0=zeroeth percentile of standard deviation values= min of sd values)

minsize

Minimum number of genes in genesets to be considered

maxsize

Maximum number of genes in genesets to be considered

restand

Should restandardization be done? Default TRUE

,

restand.basis

What should be used to do the restandardization? The set of genes in the genesets ("catalog", the default) or the genes in the data set ("data")

nperms

Number of permutations used to estimate false discovery rates

xl.mode

Used by Excel interface

xl.time

Used by Excel interface

xl.prevfit

Used by Excel interface

Details

Carries out a Gene set analysis, as described in the paper by Efron and Tibshirani (2006). It differs from a Gene Set Enrichment Analysis (Subramanian et al 2006) in its use of the "maxmean" statistic: this is the mean of the positive or negative part of gene scores in the gene set, whichever is large in absolute values. Efron and Tibshirani shows that this is often more powerful than the modified KS statistic used in GSEA. GSA also does "restandardization" of the genes (rows), on top of the permutation of columns (done in GSEA). Gene set analysis is applicable to microarray data and other data with a large number of features. This is also the R package that is called by the "official" SAM Excel package v3.0. The format of the response vector y and the calling sequence is illustrated in the examples below. A more complete description is given in the SAM manual at http://www-stat.stanford.edu/~tibs/SAM

Value

A list with components

GSA.scores

Gene set scores for each gene set

GSA.scores.perm

Matrix of Gene set scores from permutions, one column per permutation

fdr.lo

Estimated false discovery rates for negative gene sets (negative means lower expression correlates with class 2 in two sample problems, lower expression correlates with increased y for quantitative problems, lower expression correlates with higher risk for survival problems)

fdr.hi

Estimated false discovery rates for positive gene sets; positive is opposite of negative, as defined above

pvalues.lo

P-values for negative gene sets

pvalues.hi

P-values for positive gene sets

stand.info

Information from restandardization process

stand.info.star

Information from restandardization process in permutations

ngenes

Number of genes in union of gene sets

nperms

Number of permutations used

gene.scores

Individual gene scores (eg t-statistics for two class problem)

s0

Computed exchangeability factor

s0.perc

Computed percentile of standard deviation values. s0= s0.perc percentile of the gene standard deviations

call

The call to GSA

x

For internal use

y

For internal use

genesets

For internal use

genenames

For internal use

r.obs

For internal use

r.star

For internal use

gs.mat

For internal use

gs.ind

For internal use

catalog

For internal use

catalog.unique

For internal use

Author(s)

Robert Tibshirani

References

Efron, B. and Tibshirani, R. On testing the significance of sets of genes. Stanford tech report rep 2006. http://www-stat.stanford.edu/~tibs/ftp/GSA.pdf

Subramanian, A. and Tamayo, P. Mootha, V. K. and Mukherjee, S. and Ebert, B. L. and Gillette, M. A. and Paulovich, A. and Pomeroy, S. L. and Golub, T. R. and Lander, E. S. and Mesirov, J. P. (2005) A knowledge-based approach for interpreting genome-wide expression profiles. PNAS. 102, pg 15545-15550.

Examples

######### two class unpaired comparison
# y must take values 1,2

set.seed(100)
x<-matrix(rnorm(1000*20),ncol=20)
dd<-sample(1:1000,size=100)

u<-matrix(2*rnorm(100),ncol=10,nrow=100)
x[dd,11:20]<-x[dd,11:20]+u
y<-c(rep(1,10),rep(2,10))


genenames=paste("g",1:1000,sep="")

#create some random gene sets
genesets=vector("list",50)
for(i in 1:50){
 genesets[[i]]=paste("g",sample(1:1000,size=30),sep="")
}
geneset.names=paste("set",as.character(1:50),sep="")

GSA.obj<-GSA(x,y, genenames=genenames, genesets=genesets,
             resp.type="Two class unpaired", nperms=100)


GSA.listsets(GSA.obj, geneset.names=geneset.names,FDRcut=.5)



#to use  "real" gene set collection, we read it in from a gmt file:
# 
# geneset.obj<- GSA.read.gmt("file.gmt")
# 
# where file.gmt is a gene set collection from GSEA collection or
#  or the website http://www-stat.stanford.edu/~tibs/GSA, or one
# that you have created yourself. Then

#   GSA.obj<-GSA(x,y, genenames=genenames, genesets=geneset.obj$genesets,
#                resp.type="Two class unpaired", nperms=100)
#
#

"Correlates" a gene set collection with a given list of gene nams

Description

"Correlates" a gene set collection with a given list of gene names. Gives info on the overlap between the collection and the list of genes

Usage

GSA.correlate(GSA.genesets.obj, genenames)

Arguments

GSA.genesets.obj

Gene set collection, created for example by GSA.read.gmt

genenames

Vector of gene names in expression daatset

Details

Gives info on the overlap between a gene set collection and the list of gene names. This is for information purposes, to find out, for example, how many genes in the list of genes appear in the gene set collection.

Author(s)

Robert Tibshirani

References

Efron, B. and Tibshirani, R. On testing the significance of sets of genes. Stanford tech report rep 2006. http://www-stat.stanford.edu/~tibs/ftp/GSA.pdf

Examples

######### two class unpaired comparison
# y must take values 1,2

set.seed(100)
x<-matrix(rnorm(1000*20),ncol=20)
dd<-sample(1:1000,size=100)

u<-matrix(2*rnorm(100),ncol=10,nrow=100)
x[dd,11:20]<-x[dd,11:20]+u
y<-c(rep(1,10),rep(2,10))


genenames=paste("g",1:1000,sep="")

#create some random gene sets
genesets=vector("list",50)
for(i in 1:50){
 genesets[[i]]=paste("g",sample(1:1000,size=30),sep="")
}
geneset.names=paste("set",as.character(1:50),sep="")

GSA.correlate(genesets, genenames)

Gene set analysis without permutations

Description

Determines the significance of pre-defined sets of genes with respect to an outcome variable, such as a group indicator, quantitative variable or survival time. This is the basic function called by GSA.

Usage

GSA.func(x,y, genesets, genenames,geneset.names=NULL,
 method=c("maxmean","mean","absmean"),
 resp.type=c("Quantitative","Two class unpaired","Survival","Multiclass",
             "Two class paired",  "tCorr", "taCorr" ),
censoring.status=NULL,
 first.time = TRUE, return.gene.ind = TRUE, 
ngenes = NULL, gs.mat =NULL, gs.ind = NULL,
 catalog = NULL, catalog.unique =NULL, 
s0 = NULL, s0.perc = NULL, minsize = 15, maxsize= 500, restand = TRUE,
restand.basis=c("catalog","data"))

Arguments

x

Data x: p by n matrix of features, one observation per column (missing values allowed)

y

Vector of response values: 1,2 for two class problem, or 1,2,3 ... for multiclass problem, or real numbers for quantitative or survival problems

genesets

Gene set collection (a list)

genenames

Vector of genenames in expression dataset

geneset.names

Optional vector of gene set names

method

Method for summarizing a gene set: "maxmean" (default), "mean" or "absmean"

resp.type

Problem type: "quantitative" for a continuous parameter; "Two class unpaired" ; "Survival" for censored survival outcome; "Multiclass" : more than 2 groups; "Two class paired" for paired outcomes, coded -1,1 (first pair), -2,2 (second pair), etc

censoring.status

Vector of censoring status values for survival problems, 1 mean death or failure, 0 means censored)

first.time

internal use

return.gene.ind

internal use

ngenes

internal use

gs.mat

internal use

gs.ind

internal use

catalog

internal use

catalog.unique

internal use

s0

Exchangeability factor for denominator of test statistic; Default is automatic choice

s0.perc

Percentile of standard deviation values to use for s0; default is automatic choice; -1 means s0=0 (different from s0.perc=0, meaning s0=zeroeth percentile of standard deviation values= min of sd values

minsize

Minimum number of genes in genesets to be considered

maxsize

Maximum number of genes in genesets to be considered

restand

Should restandardization be done? Default TRUE

restand.basis

What should be used to do the restandardization? The set of genes in the genesets ("catalog", the default) or the genes in the data set ("data")

Details

Carries out a Gene set analysis, computing the gene set scores. This function does not do any permutations for estimation of false discovery rates. GSA calls this function to estimate FDRs.

Value

A list with components

scores

Gene set scores for each gene set

,

norm.scores

Gene set scores transformed by the inverse Gaussian cdf

,

mean

Means of gene expression values for each sample

sd

Standard deviation of gene expression values for each sample

gene.ind

List indicating whch genes in each positive gene set had positive individual scores, and similarly for negative gene sets

geneset.names

Names of the gene sets

nperms

Number of permutations used

gene.scores

Individual gene scores (eg t-statistics for two class problem)

s0

Computed exchangeability factor

s0.perc

Computed percentile of standard deviation values

stand.info

Information computed used in the restandardization process

method

Method used (from call to GSA.func)

call

The call to GSA

Author(s)

Robert Tibshirani

References

Efron, B. and Tibshirani, R. On testing the significance of sets of genes. Stanford tech report rep 2006. http://www-stat.stanford.edu/~tibs/ftp/GSA.pdf

Examples

######### two class unpaired comparison
# y must take values 1,2

set.seed(100)
x<-matrix(rnorm(1000*20),ncol=20)
dd<-sample(1:1000,size=100)

u<-matrix(2*rnorm(100),ncol=10,nrow=100)
x[dd,11:20]<-x[dd,11:20]+u
y<-c(rep(1,10),rep(2,10))


genenames=paste("g",1:1000,sep="")

#create some random gene sets
genesets=vector("list",50)
for(i in 1:50){
 genesets[[i]]=paste("g",sample(1:1000,size=30),sep="")
}
geneset.names=paste("set",as.character(1:50),sep="")

GSA.func.obj<-GSA.func(x,y, genenames=genenames, genesets=genesets,  resp.type="Two class unpaired")




#to use  "real" gene set collection, we read it in from a gmt file:
# 
# geneset.obj<- GSA.read.gmt("file.gmt")
# 
# where file.gmt is a gene set collection from GSEA collection or
#  or the website http://www-stat.stanford.edu/~tibs/GSA, or one
# that you have created yourself. Then

#   GSA.func.obj<-GSA.func(x,y, genenames=genenames,
#                          genesets=geneset.obj$genesets,
#                          resp.type="Two class unpaired")
#
#

Individual gene scores from a gene set analysis

Description

Compute individual gene scores from a gene set analysis

Usage

GSA.genescores(geneset.number, genesets,  GSA.obj,  genenames, negfirst=FALSE)

Arguments

geneset.number

Number indicating which gene set is to examined

genesets

The gene set collection

GSA.obj

Object returned by function GSA

genenames

Vector of gene names for gene in expression dataset

negfirst

Should negative genes be listed first? Default FALSE

Details

Compute individual gene scores from a gene set analysis. Useful for looking “inside” a gene set that has been called significant by GSA.

Value

A list with components

res

Matrix of gene names and gene scores (eg t-statistics) for each gene in the gene set

,

Author(s)

Robert Tibshirani

References

Efron, B. and Tibshirani, R. On testing the significance of sets of genes. Stanford tech report rep 2006. http://www-stat.stanford.edu/~tibs/ftp/GSA.pdf

Examples

######### two class unpaired comparison
# y must take values 1,2

set.seed(100)
x<-matrix(rnorm(1000*20),ncol=20)
dd<-sample(1:1000,size=100)

u<-matrix(2*rnorm(100),ncol=10,nrow=100)
x[dd,11:20]<-x[dd,11:20]+u
y<-c(rep(1,10),rep(2,10))


genenames=paste("g",1:1000,sep="")

#create some random gene sets
genesets=vector("list",50)
for(i in 1:50){
 genesets[[i]]=paste("g",sample(1:1000,size=30),sep="")
}
geneset.names=paste("set",as.character(1:50),sep="")

GSA.obj<-GSA(x,y, genenames=genenames, genesets=genesets,
             resp.type="Two class unpaired", nperms=100)

# look at 10th gene set

GSA.genescores(10, genesets, GSA.obj, genenames)

List the results from a Gene set analysis

Description

List the results from a call to GSA (Gene set analysis)

Usage

GSA.listsets(GSA.obj, geneset.names = NULL, maxchar = 20, FDRcut = 0.2)

Arguments

GSA.obj

Object returned by GSA function

.

geneset.names

Optional vector of names for the gene sets

maxchar

Maximum number of characters in printed output

FDRcut

False discovery rate cutpoint for listed sets. A value of 1 will cause all sets to be listed

.

Details

This function list the sigificant gene sets, based on a call to the GSA (Gene set analysis) function.

Value

A list with components

FDRcut

The false discovery rate threshold used.

negative

A table of the negative gene sets. "Negative" means that lower expression of most genes in the gene set correlates with higher values of the phenotype y. Eg for two classes coded 1,2, lower expression correlates with class 2. For survival data, lower expression correlates with higher risk, i.e shorter survival (Be careful, this can be confusing!)

positive

A table of the positive gene sets. "Positive" means that higher expression of most genes in the gene set correlates with higher values of the phenotype y. See "negative" above for more info.

nsets.neg

Number of negative gene sets

nsets.pos

Number of positive gene sets

Author(s)

Robert Tibshirani

References

Efron, B. and Tibshirani, R. On testing the significance of sets of genes. Stanford tech report rep 2006. http://www-stat.stanford.edu/~tibs/ftp/GSA.pdf

Examples

######### two class unpaired comparison
# y must take values 1,2

set.seed(100)
x<-matrix(rnorm(1000*20),ncol=20)
dd<-sample(1:1000,size=100)

u<-matrix(2*rnorm(100),ncol=10,nrow=100)
x[dd,11:20]<-x[dd,11:20]+u
y<-c(rep(1,10),rep(2,10))


genenames=paste("g",1:1000,sep="")

#create some radnom gene sets
genesets=vector("list",50)
for(i in 1:50){
 genesets[[i]]=paste("g",sample(1:1000,size=30),sep="")
}
geneset.names=paste("set",as.character(1:50),sep="")

GSA.obj<-GSA(x,y, genenames=genenames, genesets=genesets,
             resp.type="Two class unpaired", nperms=100)


GSA.listsets(GSA.obj, geneset.names=geneset.names,FDRcut=.5)

Creates features from a GSA analysis that can be used in other procedures

Description

Creates features from a GSA analysis that can be used in other procedures, for example, sample classification.

Usage

GSA.make.features(GSA.func.obj, x, genesets, genenames)

Arguments

GSA.func.obj

Object returned by GSA.func

x

Expression dataset from which the features are to be created

genesets

Gene set collection

genenames

Vector of gene names in expression dataset

Details

Creates features from a GSA analysis that can be used in other procedures, for example, sample classification. For example, suppose the GSA analysis computes a maxmean score for gene set 1 that is positive, based on the mean of the positive part of the scores in that gene set. Call the subset of genes with positive scores "A". Then we compute a new feature for this geneset, for each sample, by computing the mean of the scores for genes in A, setting other gene scores to zero.

Author(s)

Robert Tibshirani

References

Efron, B. and Tibshirani, R. On testing the significance of sets of genes. Stanford tech report rep 2006. http://www-stat.stanford.edu/~tibs/ftp/GSA.pdf

Examples

######### two class unpaired comparison
# y must take values 1,2

set.seed(100)
x<-matrix(rnorm(1000*20),ncol=20)
dd<-sample(1:1000,size=100)

u<-matrix(2*rnorm(100),ncol=10,nrow=100)
x[dd,11:20]<-x[dd,11:20]+u
y<-c(rep(1,10),rep(2,10))


genenames=paste("g",1:1000,sep="")

#create some random gene sets
genesets=vector("list",50)
for(i in 1:50){
 genesets[[i]]=paste("g",sample(1:1000,size=30),sep="")
}
geneset.names=paste("set",as.character(1:50),sep="")

GSA.func.obj<-GSA.func(x,y, genenames=genenames, genesets=genesets,  resp.type="Two class unpaired")


GSA.make.features(GSA.func.obj, x, genesets, genenames)

Plot the results from a Gene set analysis

Description

Plots the results from a call to GSA (Gene set analysis)

Usage

GSA.plot(GSA.obj, fac=1, FDRcut = 1)

Arguments

GSA.obj

Object returned by GSA function

.

fac

value for jittering points in plot ("factor" in called to jitter()

FDRcut

False discovery rate cutpoint for sets to be plotted. A value of 1 (the default) will cause all sets to be plotted

.

Details

This function makes a plot of the significant gene sets, based on a call to the GSA (Gene set analysis) function.

Author(s)

Robert Tibshirani

References

Efron, B. and Tibshirani, R. On testing the significance of sets of genes. Stanford tech report rep 2006. http://www-stat.stanford.edu/~tibs/ftp/GSA.pdf

Examples

######### two class unpaired comparison
# y must take values 1,2

set.seed(100)
x<-matrix(rnorm(1000*20),ncol=20)
dd<-sample(1:1000,size=100)

u<-matrix(2*rnorm(100),ncol=10,nrow=100)
x[dd,11:20]<-x[dd,11:20]+u
y<-c(rep(1,10),rep(2,10))


genenames=paste("g",1:1000,sep="")

#create some radnom gene sets
genesets=vector("list",50)
for(i in 1:50){
 genesets[[i]]=paste("g",sample(1:1000,size=30),sep="")
}
geneset.names=paste("set",as.character(1:50),sep="")

GSA.obj<-GSA(x,y, genenames=genenames, genesets=genesets,
             resp.type="Two class unpaired", nperms=100)


GSA.listsets(GSA.obj, geneset.names=geneset.names,FDRcut=.5)

GSA.plot(GSA.obj)

Read in a gene set collection from a .gmt file

Description

Read in a gene set collection from a .gmt file

Usage

GSA.read.gmt(filename)

Arguments

filename

The name of a file to read data values from. Should be a tab-separated text file, with one row per gene set. Column 1 has gene set names (identifiers), column 2 has gene set descriptions, remaining columns are gene ids for genes in that geneset

.

Details

This function reads in a geneset collection from a .gmt text file, and creates an R object that can be used as input into GSA. We use UniGene symbols for our gene set names in our .gmt files and expression datasets, to match the two. However the user is free to use other identifiers, as long as the same ones are used in the gene set collections and expression datasets.

Value

A list with components

genesets

List of gene names (identifiers) in each gene set

,

geneset.names

Vector of gene set names (identifiers)

,

geneset.descriptions

Vector of gene set descriptions

Author(s)

Robert Tibshirani

References

Efron, B. and Tibshirani, R. On testing the significance of sets of genes. Stanford tech report rep 2006. http://www-stat.stanford.edu/~tibs/ftp/GSA.pdf

Examples

# read in  functional pathways gene set file from Broad institute GSEA website
# http://www.broad.mit.edu/gsea/msigdb/msigdb_index.html
# You have to register first and then download the file C2.gmt from
#   their site

#GSA.read.gmt(C2.gmt)