runWF: Run the Entire GESS/FEA Workflow

In girke-lab/signatureSearch: Environment for Gene Expression Searching Combined with Functional Enrichment Analysis

Run the Entire GESS/FEA Workflow

Description

This function runs the entire GESS/FEA workflow when providing the query drug and cell type, as well as selecting the reference database (e.g. 'cmap' or 'lincs'), defining the specific GESS and FEA methods. In this case, the query GES is drawn from the reference database. The N (defined by the 'N_gess_drugs' argument) top ranking hits in the GESS tables were then used for FEA where three different annotation systems were used: GO Molecular Function (GO MF), GO Biological Process (GO BP) and KEGG pathways.

The GESS/FEA results will be stored in a list object in R session. A working environment named by the use case will be created under users current working directory or under other directory defined by users. This environment contains a results folder where the GESS/FEA result tables were written to. The working environment also contains a template Rmd vignette as well as a rended HTML report, users could make modifications on the Rmd vignette as they need and re-render it to generate their HTML report.

Usage

runWF(
  Signature,
  cellInfo,
  PertColName = "pert_iname",
  drug,
  refdb,
  gess_method = "LINCS",
  fea_method = "dup_hyperG",
  N_gess_drugs = 150,
  env_dir = ".",
  tau = FALSE,
  Nup = 150,
  Ndown = 150,
  higher = 1,
  lower = -1,
  method = "spearman",
  pvalueCutoff = 1,
  qvalueCutoff = 1,
  minGSSize = 5,
  maxGSSize = 500,
  runFEA = TRUE,
  GenerateReport = TRUE
)

Arguments

Signature	The signature to perform signatureSearching on.
cellInfo	A data table containing information about the cell types that make up the signature search database. This table must contain a column labeled "cell_id" that contains matching cell type names in the signature search database. Details about this file can be found in the cell_info2 table after load the 'signatureSearch' package and running 'data("cell_info2")'
PertColName	The name of the column from the signature search results table used to summarize results by.
drug	character(1) representing query drug name (e.g. vorinostat). This query drug should be included in the refdb
refdb	character(1), one of "lincs", "lincs_expr", "cmap", "cmap_expr", or path to the HDF5 file built from build_custom_db function
gess_method	character(1), one of "LINCS", "CORsub", "CORall", "Fisher", "CMAP", "gCMAP". When gess_method is "CORsub" or "CORall", only "lincs_expr" or "cmap_expr" databases are supported.
fea_method	character(1), one of "dup_hyperG", "mGSEA", "mabs", "hyperG", "GSEA"
N_gess_drugs	number of unique drugs in GESS result used as input of FEA
env_dir	character(1), directory under which the result environment located. The default is users current working directory in R session, can be checked via getwd() command in R
tau	TRUE or FALSE indicating whether to compute Tau scores if gess_method is set as 'LINCS'
Nup	integer(1). Number of most up-regulated genes to be subsetted for GESS query when gess_method is CMAP, LINCS or CORsub
Ndown	integer(1). Number of most down-regulated genes to be subsetted for GESS query when gess_method is CMAP, LINCS or CORsub
higher	numeric(1), it is defined when gess_method argument is 'gCMAP' or 'Fisher' representing the 'upper' threshold of subsetting genes with a score larger than 'higher'
lower	numeric(1), it is defined when gess_method argument is 'gCMAP' or 'Fisher' representing the 'lower' threshold of subsetting genes
method	One of 'spearman' (default), 'kendall', or 'pearson', indicating which correlation coefficient to use
pvalueCutoff	double, p-value cutoff for FEA result
qvalueCutoff	double, qvalue cutoff for FEA result
minGSSize	integer, minimum size of each gene set in annotation system
maxGSSize	integer, maximum size of each gene set in annotation system
runFEA	Logical value indicating if FEA analysis is performed.
GenerateReport	Logical value indicating if a report is generated.

Value

list object containing GESS/FEA result tables

Examples

library(signatureSearch)
library(ExperimentHub); library(rhdf5)
eh <- ExperimentHub()
cmap <- eh[["EH3223"]]; cmap_expr <- eh[["EH3224"]]
lincs <- eh[["EH3226"]]; lincs_expr <- eh[["EH3227"]]
lincs2 <- eh[["EH7297"]]
h5ls(lincs2)
db_path <- system.file("extdata", "sample_db.h5", package = "signatureSearch")
library(SummarizedExperiment);
library(HDF5Array)
sample_db <- SummarizedExperiment(HDF5Array(db_path, name="assay"))
rownames(sample_db) <- HDF5Array(db_path, name="rownames")
colnames(sample_db) <- HDF5Array(db_path, name="colnames")
query_mat <- as.matrix(assay(sample_db[,"vorinostat__SKB__trt_cp"]))
query <- as.numeric(query_mat); names(query) <- rownames(query_mat)
upset <- head(names(query[order(-query)]), 150)
head(upset)
downset <- tail(names(query[order(-query)]), 150)
head(downset)
runWF(Signature = list(upset=upset, downset=downset),
      cellInfo = cellInfo2,
      PertColName = "pert_iname",
      drug = "vorinostat",
      refdb = lincs2,
      gess_method="LINCS",
      fea_method="dup_hyperG",
      N_gess_drugs=150,
      env_dir="./GESSWFResults",
      tau=FALSE,
      Nup=150,
      Ndown=150,
      higher=1,
      lower=-1,
      method="spearman",
      pvalueCutoff=1,
      qvalueCutoff=1,
      minGSSize=5,
      maxGSSize=500,
      runFEA=TRUE,
      GenerateReport= TRUE)

girke-lab/signatureSearch documentation built on Feb. 21, 2024, 8:32 a.m.