filterGRNAndConnectGenes: Filter the GRN and integrate peak-gene connections.

In chrarnold/GRaNIE: GRaNIE: Reconstruction cell type specific gene regulatory networks including enhancers using chromatin accessibility and RNA-seq data

Filter the GRN and integrate peak-gene connections.

Description

This is one of the main integrative functions of the GRN package. It has two main functions: Filtering the TF-peak and peak-gene connections that have been identified before, and combining the 3 major elements (TFs, peaks, genes) into one data frame, with one row per connection. Here, a connection can either be a TF-peak, peak-gene or TF-peak-gene link, depending on the parameters. Internally, first, the TF-peak are filtered before the peak-gene connections are added for reasons of memory and computational efficacy: It takes a lot of time and particularly space to connect the full GRN with all peak-gene connections - as most of the links have weak support (i.e., high FDR), first filtering out unwanted links dramatically reduces the memory needed for the combined GRN

Usage

filterGRNAndConnectGenes(
  GRN,
  TF_peak.fdr.threshold = 0.2,
  TF_peak.connectionTypes = "all",
  peak_gene.p_raw.threshold = NULL,
  peak_gene.fdr.threshold = 0.2,
  peak_gene.fdr.method = "BH",
  peak_gene.IHW.covariate = NULL,
  peak_gene.IHW.nbins = 5,
  gene.types = c("protein_coding", "lincRNA"),
  allowMissingTFs = FALSE,
  allowMissingGenes = TRUE,
  peak_gene.r_range = c(0, 1),
  peak_gene.selection = "all",
  peak_gene.maxDistance = NULL,
  filterTFs = NULL,
  filterGenes = NULL,
  filterPeaks = NULL,
  TF_peak_FDR_selectViaCorBins = FALSE,
  filterLoops = TRUE,
  outputFolder = NULL,
  silent = FALSE
)

Arguments

GRN	Object of class GRN
TF_peak.fdr.threshold	Numeric[0,1]. Default 0.2. Maximum FDR for the TF-peak links. Set to 1 or NULL to disable this filter.
TF_peak.connectionTypes	Character vector. Default all. TF-peak connection types to consider. The special keyword all denotes all connection types (e.g., expression and TFActivity) that are found in the GRN object. By default, only expression is present in the object, so all and expression are usually equivalent unless calculation of TF-peak links based on TF activity has also been enabled.
peak_gene.p_raw.threshold	Numeric[0,1]. Default NULL. Threshold for the peak-gene connections, based on the raw p-value. All peak-gene connections with a larger raw p-value will be filtered out.
peak_gene.fdr.threshold	Numeric[0,1]. Default 0.2. Threshold for the peak-gene connections, based on the FDR. All peak-gene connections with a larger FDR will be filtered out.
peak_gene.fdr.method	Character. Default "BH". One of: "holm", "hochberg", "hommel", "bonferroni", "BH", "BY", "fdr", "none", "IHW". Method for adjusting p-values for multiple testing. If set to "IHW", independent hypothesis weighting will be performed, and a suitable covariate has to be specified for the parameter peak_gene.IHW.covariate.
peak_gene.IHW.covariate	Character. Default NULL. Name of the covariate to use for IHW (column name from the table thatis returned with the function getGRNConnections. Only relevant if peak_gene.fdr.method is set to "IHW". You have to make sure the specified covariate is suitable or IHW, see the diagnostic plots that are generated in this function for this. For many datasets, the peak-gene distance (called peak_gene.distance in the object) seems suitable.
peak_gene.IHW.nbins	Integer or "auto". Default 5. Number of bins for IHW. Only relevant if peak_gene.fdr.method is set to "IHW".
gene.types	Character vector of supported gene types. Default c("protein_coding", "lincRNA"). Filter for gene types to retain, genes with other gene types are filtered.
allowMissingTFs	TRUE or FALSE. Default FALSE. Should connections be returned for which the TF is NA (i.e., connections consisting only of peak-gene links?). If set to TRUE, this generally greatly increases the number of connections but it may not be what you aim for.
allowMissingGenes	TRUE or FALSE. Default TRUE. Should connections be returned for which the gene is NA (i.e., connections consisting only of TF-peak links?). If set to TRUE, this generally increases the number of connections.
peak_gene.r_range	Numeric(2). Default c(0,1). Filter for lower and upper limit for the peak-gene links. Only links will be retained if the correlation coefficient is within the specified interval. This filter is usually used to filter out negatively correlated peak-gene links.
peak_gene.selection	"all" or "closest". Default "all". Filter for the selection of genes for each peak. If set to "all", all previously identified peak-gene are used, while "closest" only retains the closest gene for each peak that is retained until the point the filter is applied.
peak_gene.maxDistance	Integer >0. Default NULL. Maximum peak-gene distance to retain a peak-gene connection.
filterTFs	Character vector. Default NULL. Vector of TFs (as named in the GRN object) to retain. All TFs not listed will be filtered out.
filterGenes	Character vector. Default NULL. Vector of gene IDs (as named in the GRN object) to retain. All genes not listed will be filtered out.
filterPeaks	Character vector. Default NULL. Vector of peak IDs (as named in the GRN object) to retain. All peaks not listed will be filtered out.
TF_peak_FDR_selectViaCorBins	TRUE or FALSE. Default FALSE. Use a modified procedure for selecting TF-peak links that is based on the user-specified FDR but that retains also links that may have a higher FDR but a more extreme correlation.
filterLoops	TRUE or FALSE. Default TRUE. If a TF regulates itself (i.e., the TF and the gene are the same entity), should such loops be filtered from the GRN?
outputFolder	Character or NULL. Default NULL. If set to NULL, the default output folder as specified when initiating the object in link{initializeGRN} will be used. Otherwise, all output from this function will be put into the specified folder. We recommend specifying an absolute path.
silent	TRUE or FALSE. Default FALSE. Print progress messages and filter statistics.

Value

The same GRN object, with the filtered and merged TF-peak and peak-gene connections in the slot connections$all.filtered.

See Also

visualizeGRN

addConnections_TF_peak

addConnections_peak_gene

Examples

# See the Workflow vignette on the GRaNIE website for examples
GRN = loadExampleObject()
GRN = filterGRNAndConnectGenes(GRN)

chrarnold/GRaNIE documentation built on April 28, 2022, 2:18 a.m.