GOHyperGAll: GO term enrichment analysis for large numbers of gene sets

In tgirke/systemPipeR: systemPipeR: Workflow Environment for Data Analysis and Report Generation

GO term enrichment analysis for large numbers of gene sets

Description

To test a sample population of genes for over-representation of GO terms, the core function GOHyperGAll computes for all nodes in the three GO networks (BP, CC and MF) an enrichment test based on the hypergeometric distribution and returns the corresponding raw and Bonferroni corrected p-values. Subsequently, a filter function supports GO Slim analyses using default or custom GO Slim categories. Several convenience functions are provided to process large numbers of gene sets (e.g. clusters from partitioning results) and to visualize the results.

Note: GOHyperGAll provides similar utilities as the GOHyperG function in the GOstats package. The main difference is that GOHyperGAll simplifies processing of large numbers of gene sets, as well as the usage of custom array-to-gene and gene-to-GO mappings.

Usage

## Generate gene-to-GO mappings and store as catDB object 
makeCATdb(myfile, lib = NULL, org = "", colno = c(1, 2, 3), idconv = NULL, 
            rootUK=FALSE)

## Enrichment function
GOHyperGAll(catdb, gocat = "MF", sample, Nannot = 2)

## GO slim analysis
GOHyperGAll_Subset(catdb, GOHyperGAll_result, sample = test_sample, 
            type = "goSlim", myslimv)

## Reduce GO term redundancy 
GOHyperGAll_Simplify(GOHyperGAll_result, gocat = "MF", cutoff = 0.001, correct = TRUE)

## Batch analysis of many gene sets
GOCluster_Report(catdb, setlist, id_type = "affy", method = "all", CLSZ = 10, 
            cutoff = 0.001, gocats = c("MF", "BP", "CC"), myslimv = "default",
            correct = TRUE, recordSpecGO = NULL, ...)

## Bar plot of GOCluster_Report results
goBarplot(GOBatchResult, gocat)

Arguments

myfile	File with gene-to-GO mappings. Sample files can be downloaded from geneontology.org (http://geneontology.org/GO.downloads.annotations.shtml) or from BioMart as shown in example below.
colno	Column numbers referencing in myfile the three target columns containing GOID, GeneID and GOCAT, in that order.
org	Optional argument. Currently, the only valid option is org="Arabidopsis" to get rid of transcript duplications in this particular annotation.
lib	If the gene-to-GO mappings are obtained from a *.db package from Bioconductor then the package name can be specified under the lib argument of the sampleDFgene2GO function.
idconv	Optional id conversion data.frame
catdb	catdb object storing mappings of genes to annotation categories. For details, see ?"SYSargs-class".
rootUK	If the argument rootUK is set to TRUE then the root nodes are treated as terminal nodes to account for the new unknown terms.
sample	character vector containing the test set of gene identifiers
Nannot	Defines the minimum number of direct annotations per GO node from the sample set to determine the number of tested hypotheses for the p-value adjustment.
gocat	Specifies the GO type, can be assigned one of the following character values: "MF", "BP" and "CC".
GOHyperGAll_result	data.frame generated by GOHyperGAll
type	The function GOHyperGAll_Subset subsets the GOHyperGAll results by directly assigned GO nodes or custom goSlim categories. The argument type can be assigned the values goSlim or assigned.
myslimv	optional argument to provide custom goSlim vector
cutoff	p-value cutoff for GO terms to show in result data.frame
correct	If TRUE the function will favor the selection of terminal (informationich) GO terms that have at the same time a large number of sample matches.
setlist	list of character vectors containing gene IDs (or array feature IDs). The names of the list components correspond to the set labels, e.g. DEG comparisons or cluster IDs.
id_type	specifies type of IDs in input, can be assigned gene or affy
method	Specifies analysis type. Current options are all for GOHyperGAll, slim for GOHyperGAll_Subset or simplify for GOHyperGAll_Simplify.
CLSZ	minimum gene set (cluster) size to consider. Gene sets below this cutoff will be ignored.
gocats	Specifies GO type, can be assigned the values "MF", "BP" and "CC".
recordSpecGO	argument to report in the result data.frame specific GO IDs for any of the 3 ontologies disregarding whether they meet the specified p-value cutoff, e.g: recordSpecGO=c("GO:0003674", "GO:0008150", "GO:0005575")
GOBatchResult	data.frame generated by GOCluster_Report
...	additional arguments to pass on

Details

GOHyperGAll_Simplify: The result data frame from GOHyperGAll will often contain several connected GO terms with significant scores which can complicate the interpretation of large sample sets. To reduce this redundancy, the function GOHyperGAll_Simplify subsets the data frame by a user specified p-value cutoff and removes from it all GO nodes with overlapping children sets (OFFSPRING), while the best scoring nodes are retained in the result data.frame.

GOCluster_Report: performs the three types of GO term enrichment analyses in batch mode: GOHyperGAll, GOHyperGAll_Subset or GOHyperGAll_Simplify. It processes many gene sets (e.g. gene expression clusters) and returns the results conveniently organized in a single result data frame.

Value

makeCATdb generates catDB object from file.

Author(s)

Thomas Girke

References

This workflow has been published in Plant Physiol (2008) 147, 41-57.

See Also

GOHyperGAll_Subset, GOHyperGAll_Simplify, GOCluster_Report, goBarplot

Examples

## Not run: 

## Obtain annotations from BioMart
listMarts() # To choose BioMart database
m <- useMart("ENSEMBL_MART_PLANT"); listDatasets(m) 
m <- useMart("ENSEMBL_MART_PLANT", dataset="athaliana_eg_gene")
listAttributes(m) # Choose data types you want to download
go <- getBM(attributes=c("go_accession", "tair_locus", 
            "go_namespace_1003"), mart=m)
go <- go[go[,3]!="",]; go[,3] <- as.character(go[,3])
write.table(go, "GOannotationsBiomart_mod.txt", quote=FALSE, 
            row.names=FALSE, col.names=FALSE, sep="\t")

## Create catDB instance (takes a while but needs to be done only once)
catdb <- makeCATdb(myfile="GOannotationsBiomart_mod.txt", lib=NULL, org="",
                    colno=c(1,2,3), idconv=NULL)
catdb

## Create catDB from Bioconductor annotation package
# catdb <- makeCATdb(myfile=NULL, lib="ath1121501.db", org="", 
                    colno=c(1,2,3), idconv=NULL)

## AffyID-to-GeneID mappings when working with AffyIDs 
# affy2locusDF <- systemPipeR:::.AffyID2GeneID(map = "ftp://ftp.arabidopsis.org/home/tair/Microarrays/Affymetrix/affy_ATH1_array_elements-2010-12-20.txt",
                                                download=TRUE)
# catdb_conv <- makeCATdb(myfile="GOannotationsBiomart_mod.txt", lib=NULL, org="", 
                            colno=c(1,2,3), idconv=list(affy=affy2locusDF))
# systemPipeR:::.AffyID2GeneID(catdb=catdb_conv, 
                                affyIDs=c("244901_at", "244902_at"))

## Next time catDB can be loaded from file
save(catdb, file="catdb.RData") 
load("catdb.RData")

## Perform enrichment test on single gene set
test_sample <- unique(as.character(catmap(catdb)$D_MF[1:100,"GeneID"]))
GOHyperGAll(catdb=catdb, gocat="MF", sample=test_sample, Nannot=2)[1:20,]

## GO Slim analysis by subsetting results accordingly
GOHyperGAll_result <- GOHyperGAll(catdb=catdb, gocat="MF", sample=test_sample, Nannot=2)
GOHyperGAll_Subset(catdb, GOHyperGAll_result, sample=test_sample, type="goSlim") 

## Reduce GO term redundancy in 'GOHyperGAll_results'
simplifyDF <- GOHyperGAll_Simplify(GOHyperGAll_result, gocat="MF", 
                                    cutoff=0.001, correct=T)
# Returns the redundancy reduced data set. 
data.frame(GOHyperGAll_result[GOHyperGAll_result[,1] 

## Batch Analysis of Gene Clusters
testlist <- list(Set1=test_sample)
GOBatchResult <- GOCluster_Report(catdb=catdb, setlist=testlist, method="all", 
                                    id_type="gene", CLSZ=10, cutoff=0.001, 
                                    gocats=c("MF", "BP", "CC"), 
                                    recordSpecGO=c("GO:0003674", "GO:0008150", "GO:0005575"))

## Plot 'GOBatchResult' as bar plot
goBarplot(GOBatchResult, gocat="MF")


## End(Not run)

tgirke/systemPipeR documentation built on Sept. 24, 2024, 9:48 a.m.