predictTargetingDrugs: Predict targeting drugs

In cTRAP: Identification of candidate causal perturbations from differential gene expression data

Description

Identify compounds that may target the phenotype associated with a user-provided differential expression profile by comparing such against a correlation matrix of gene expression and drug sensitivity.

Usage

predictTargetingDrugs(
  input,
  expressionDrugSensitivityCor,
  method = c("spearman", "pearson", "gsea"),
  geneSize = 150,
  isDrugActivityDirectlyProportionalToSensitivity = NULL
)

Arguments

input	Named numeric vector of differentially expressed genes whose names are gene identifiers and respective values are a statistic that represents significance and magnitude of differentially expressed genes (e.g. t-statistics); or character of gene symbols composing a gene set that is tested for enrichment in reference data (only used if method includes gsea)
expressionDrugSensitivityCor	Matrix: correlation matrix of gene expression (rows) and drug sensitivity (columns) across cell lines. Pre-prepared gene expression and drug sensitivity associations are available to download using loadExpressionDrugSensitivityAssociation().
method	Character: one or more methods to compare data (spearman, pearson or gsea)
geneSize	Numeric: number of top up-/down-regulated genes to use as gene sets to test for enrichment in reference data; if a 2-length numeric vector, the first index is the number of top up-regulated genes and the second index is the number of down-regulated genes used to create gene sets; only used if method includes gsea and if input is not a gene set
isDrugActivityDirectlyProportionalToSensitivity	Boolean: are the values used for drug activity directly proportional to drug sensitivity? See details.

Details

If isDrugActivityDirectlyProportionalToSensitivity = NULL, the attribute isDrugMetricDirectlyProportionalToSensitivity of expressionDrugSensitivityCor is used (see loadExpressionDrugSensitivityAssociation()).

Value

Data table with correlation or GSEA results comparing differential expression values against gene expression and drug sensitivity associations

GSEA score

Weighted connectivity scores (WTCS) are calculated when method = "gsea" (https://clue.io/connectopedia/cmap_algorithms).

See Also

Other functions related with the prediction of targeting drugs: as.table.referenceComparison(), listExpressionDrugSensitivityAssociation(), loadExpressionDrugSensitivityAssociation(), plot.referenceComparison(), plotTargetingDrugsVSsimilarPerturbations()

Examples

# Example of a differential expression profile
data("diffExprStat")

# Load expression and drug sensitivity association derived from GDSC data
gdsc <- loadExpressionDrugSensitivityAssociation("GDSC 7")

# Predict targeting drugs on a differential expression profile
predictTargetingDrugs(diffExprStat, gdsc)

cTRAP documentation built on Nov. 8, 2020, 10:58 p.m.