GOHyperGAll: GO term enrichment analysis for large numbers of gene sets
In systemPipeR: systemPipeR: NGS workflow and report generation environment

Description Usage Arguments Details Value Author(s) References See Also Examples

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.

## 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)

`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

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.

makeCATdb generates catDB object from file.

Thomas Girke

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

GOHyperGAll_Subset, GOHyperGAll_Simplify, GOCluster_Report, goBarplot

## 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)