Multiple testing on the GO graph {GlobalAncova} | R Documentation

## Multiple testing on the GO graph

### Description

Three functions adapted from package globaltest to test (part of) the GO graph for association of the gene expression profile of GO terms with a response variable. Used together, these functions return multiplicity-adjusted p-values calculated using the Focus Level procedure that preserves the structure of the GO graph.

### Usage

      GAGO(..., GO, focus, maxalpha = 0.05, stopafter = 100, verbose = FALSE)
      makeGOstructure(data, annotation, top, only.ids, ontology = c("BP", "CC", "MF"), unreliable)
      getFocus(GOstructure, maxatoms = 10)

### Arguments

`...` | Arguments describing the tests to be performed are passed on to `GlobalAncova`. Note that only the approximative version of `GlobalAncova` is used here and hence the parameter `method` is not available. Even though the number of permutations (`perm`) may be specified since very large gene sets (with more genes than `max.group.size`) are treated with the permutation test.
`GO` | An object of class `GOstructure` describing the structure of the GO graph. This object should be created using `makeGOstructure`.
`focus` | A vector of GO ids to describe te focus level. Typically made using `getFocus`.
`maxalpha` | The maximum multiplicity-adjusted p-value. The algorithm will stop when this value is exceeded.
`stopafter` | The maximum number of significant GO terms to be found. The algorithm will stop when this value is exceeded.
`verbose` | If set to `TRUE`, prints much more extensive progress information.
`data` | The data set for which the `GOstructure` object is to be made. Can be either an `exprSet` or a vector of probe indicators.
`annotation` | The name of the metaData annotation package to be used, or a vector of EntrezGene ids with the same length as the number of genes in `data`.
`top` | The node to be used as top node of the `GOstructure`. Defaults to one of "GO:0008150", "GO:0005575", "GO:0003674", depending on he ontology chosen. The `GOstructure` object will only contain offspring of the chosen top node.
`only.ids` | A vector of GO ids. If this is supplied, GO ids not appearing in this list will not appear in the `GOstructure` object.
`ontology` | The ontology to be used. One of Biological Process (BP), Cellular Component (CC) or Molecular Function (MF).
`unreliable` | Can be used to designate one or more of the GO evidence codes as unreliable. Value must be a vector containing one or more from "IC", "IDA", "IEA", "IEP", "IGI", "IMP", "IPI", "ISS", "NAS", "ND", "RCA", "TAS", "NR".
`GOstructure` | An object of class `GOstructure`.
`maxatoms` | A tuning parameter that governs the choice of the focus level. `getFocus` will choose those GO terms in the focus level in such a way that all offspring gene sets of each focus level term can be constructed as unions of no more than `maxatoms` atom gene sets. Default value of `maxatoms` is 10. Higher values quickly lead to slower computation. Lower values typically lead to reduced power.

### Details

These functions should be used in the following order. First use `makeGOstructure` to make a GO graph tailored to a specific data set. Then `getFocus` can be used to choose a focus level. Finally `GAGO` performs the focus level procedure.

### Value

The function returns a named vector of multiplicity-adjusted p-values. Adjusted p-values of GO terms not appearing in this vector are larger than the chosen value of `maxalpha`.

### Note

Function `GAGO` corresponds to function `gtGO` in package globaltest. The difference is in the use of the `GlobalAncova` test instead of `globaltest` within the focus level procedure.

### Author(s)

Jelle Goeman: j.j.goeman@lumc.nl; Jan Oosting; Manuela Hummel

### References

Goeman, J.J. and Mansmann, U., Family-wise error rate on the directed acyclic graph of Gene Ontology, submitted.

### See Also

`gtGO`, `GlobalAncova`, `globaltest`, `GOstructure`

### Examples

      # see vignettes of packages GlobalAncova and globaltest and help of gtGO

[Package GlobalAncova version 3.2.0 Index]