analyze2DTPP: Analyze a 2D-TPP experiment

Description Usage Arguments Details Value References Examples

View source: R/analyze2DTPP.R

Description

Performs the whole analysis workflow for 2D-TPP experiment by invoking routines for data import, data processing, fold change computation, median normalization, TPP-CCR curve fitting, plotting and production of the result table.

Usage

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analyze2DTPP(configTable, data = NULL, resultPath = NULL,
  idVar = "gene_name", fcStr = NULL, intensityStr = "signal_sum_",
  naStrs = c("NA", "n/d", "NaN", "<NA>"), methods = "doseResponse",
  qualColName = "qupm", compFc = TRUE, normalize = TRUE,
  addCol = NULL, nCores = 1, nonZeroCols = "qssm",
  fcTolerance = 0.1, r2Cutoff = 0.8, fcCutoff = 1.5,
  slopeBounds = c(1, 50), fractAbund = FALSE, xlsxExport = TRUE,
  plotAll = FALSE, plotAllR2 = FALSE, plotSingle = FALSE,
  trRef = NULL, refFcStr = "norm_rel_fc_", addInfo = FALSE,
  createReport = "none", paletteName = "Spectral", configFile)

Arguments

configTable

dataframe, or character object with the path to a file, that specifies important details of the 2D-TPP experiment. See Section details for instructions how to create this object.

data

single dataframe, containing fold change measurements and additional annotation columns to be imported. Can be used instead of specifying the file path in the configTable argument.

resultPath

location where to store dose-response curve plots and results table.

idVar

character string indicating which data column provides the unique identifiers for each protein.

fcStr

character string indicating which columns contain the actual fold change values. Those column names containing the prefix fcStr will be regarded as containing fold change values. Only relevant if compFC = FALSE.

intensityStr

character string indicating which columns contain the actual sumionarea values. Those column names containing the prefix intensityStr will be regarded as containing sumionarea values.

naStrs

character vector indicating missing values in the data table. When reading data from file, this value will be passed on to the argument na.strings in function read.delim.

methods

vector of character strings that indicate which methods should be used for the analysis (default: c("doseResponse"), alternative: c("splineFit") or c("doseResponse", "splineFit"))

qualColName

character string indicating which column can be used for additional quality criteria when deciding between different non-unique protein identifiers.

compFc

boolean flag which indicates whether to perform fold change computation regarding reference column from sumionareas (default: TRUE)

normalize

perform median normalization (default: TRUE).

addCol

character vector indicating which additional columns to include from the input data

nCores

either a numerical value given the desired number of CPUs, or 'max' to automatically assign the maximum possible number (default).

nonZeroCols

character string indicating a column that will be used for filtering out zero values.

fcTolerance

tolerance for the fcCutoff parameter. See details.

r2Cutoff

Quality criterion on dose response curve fit.

fcCutoff

Cutoff for highest compound concentration fold change.

slopeBounds

Bounds on the slope parameter for dose response curve fitting.

fractAbund

boolean variable, if set to TRUE additional information concerning sumionarea fractional abundance and dmso1 vs. dmso2 of adjacent temperatures is added to the output table

xlsxExport

produce results table in xlsx format and store at the location specified by the resultPath argument.

plotAll

boolean value indicating whether all dose response curves should be generated. Deactivating plotting decreases runtime.

plotAllR2

boolean value indicating whether all dose response curves which fulfill the demanded criteria (Rsquared, maximum plateau) should be generated. Deactivating plotting decreases runtime.

plotSingle

boolean value indicating whether all dose response curves which fulfill the demanded criteria (Rsquared, maximum plateau) should be generated. Deactivating plotting decreases runtime.

trRef

character string containing a valid system path to a previously generated TPP-TR reference object

refFcStr

character string indicating which columns in the reference data set contain the fold change values

addInfo

boolean variable, if set to TRUE additional information on counts of stabilization and destabilization of each protein is added to the output table

createReport

character string indicating whether a markdown report should be created and which format it have (default: "html_document", alternative: "pdf_document" or "none")

paletteName

color palette (see details).

configFile

DEPRECATED

Details

Invokes the following steps:

  1. Import data using the tpp2dImport function.

  2. Remove zero sumionarea values.

  3. Compute fold changes from raw data (sumionarea)

  4. Perform normalization by fold change medians (optional) using the tpp2dNormalize function. To perform normalization, set argument normalize=TRUE.

paletteName specifies the color palette to be used by the brewer.pal function from the RColorBrewer package to assign a separate color to each concentration.

Value

A data frame in which the model results (slopes and pEC50 values) are stored row-wise for each protein and administered temperatures.

References

Becher, I., Werner, T., Doce, C., Zaal, E. A., Berkers, C. R., T"ogel, I., Salzer, E., Bantscheff, M., Savitski, M. M. (2016) Thermal profiling reveals phenylalanine hydroxylase as an off-target of panobinostat. Nature Chemical Biology, 12(11), 908-910.

Examples

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data(panobinostat_2DTPP_smallExample)
config_tpp2d <- panobinostat_2DTPP_config
data_tpp2d <- panobinostat_2DTPP_data
tpp2dResults <- analyze2DTPP(configTable = config_tpp2d, 
                             data = data_tpp2d,
                             methods=c("doseResponse"),
                             createReport="none",
                             nCores=1,
                             idVar = "representative",
                             addCol = "clustername",
                             intensityStr = "sumionarea_protein_",
                             nonZeroCols = "qusm")

DoroChilds/TPP documentation built on Oct. 16, 2019, 9:28 a.m.