dsea_GSEA: Drug Set Enrichment Analysis (DSEA) with GSEA Algorithm

In signatureSearch: Environment for Gene Expression Searching Combined with Functional Enrichment Analysis

Description

The dsea_GSEA function performs Drug Set Enrichment Analysis (DSEA) with the GSEA algorithm from Subramanian et al. (2005). In case of DSEA, drug identifiers combined with their ranking scores of an upstream GESS method are used, such as the NCS values from the LINCS method. To use drug instead of gene labels for GSEA, the former are mapped to functional categories, including GO or KEGG, based on drug-target interaction annotations provided by databases such as DrugBank, ChEMBL, CLUE or STITCH.

Usage

dsea_GSEA(
  drugList,
  type = "GO",
  ont = "BP",
  exponent = 1,
  nPerm = 1000,
  minGSSize = 10,
  maxGSSize = 500,
  pvalueCutoff = 0.05,
  pAdjustMethod = "BH"
)

Arguments

drugList	named numeric vector, where the names represent drug labels and the numeric component scores. This can be all drugs of a GESS result that are ranked by GESS scores, such as NCSs of the LINCS method. Note, drugs with scores of zero are ignored by this method.
type	one of 'GO', 'KEGG' or 'MOA'
ont	character(1). If type is 'GO', assign ont (ontology) one of ‘BP','MF', 'CC' or 'ALL'. If type is ’KEGG', ont is ignored.
exponent	integer value used as exponent in GSEA algorithm. It defines the weight of the items in the item set S. Note, in DSEA the items are drug labels, while it is gene labels in the original GSEA.
nPerm	integer defining the number of permutation iterations for calculating p-values
minGSSize	integer, annotation categories with less than minGSize drugs annotated will be ignored by enrichment test. If type is 'MOA', it may be beneficial to set 'minGSSize' to lower values (e.g. 2) than for other functional annotation systems. This is because certain MOA categories contain only 2 drugs.
maxGSSize	integer, annotation categories with more drugs annotated than maxGSize will be ignored by enrichment test.
pvalueCutoff	double, p-value cutoff to return only enrichment results for drugs meeting a user definable confidence threshold
pAdjustMethod	p-value adjustment method, one of 'holm', 'hochberg', 'hommel', 'bonferroni', 'BH', 'BY', 'fdr'

Details

The DSEA results stored in the feaResult object can be returned with the result method in tabular format, here tibble. The columns of this tibble are described in the help of the tsea_mGSEA function.

Value

feaResult object containing the enrichment results of functional categories (e.g. GO terms or KEGG pathways) ranked by the corresponding enrichment statistic.

References

GSEA algorithm: Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Mesirov, J. P. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America, 102(43), 15545-15550. URL: https://doi.org/10.1073/pnas.0506580102

See Also

feaResult, fea, GO_DATA_drug

Examples

data(drugs10)
dl <- c(rev(seq(0.1, 0.5, by=0.05)), 0)
names(dl)=drugs10
## KEGG annotation system
#gsea_k_res <- dsea_GSEA(drugList=dl, type="KEGG", exponent=1, nPerm=100, 
#                        pvalueCutoff=0.5, minGSSize=2)
#result(gsea_k_res)

signatureSearch documentation built on April 16, 2021, 6 p.m.