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Compute Transcription Factor (TF) activity

compute.TFs.activity.Rd

Infers transcription factor (TF) activity from a gene expression matrix with decoupleR::decouple(), keeping the consensus score (ensemble of the decoupleR statistics; Badia-i-Mompel et al., 2022). The TF-target network can be provided by the user, obtained from OmnipathR resources (CollecTRI or Dorothea), or read from an ARACNe-inferred network.

Usage

compute.TFs.activity(
  RNA.counts,
  TF.collection = "CollecTRI",
  min_targets_size = 5,
  universe = NULL,
  cancer.type = NULL,
  scale = TRUE,
  return = TRUE,
  file.name = NULL
)

Arguments

RNA.counts

A gene expression matrix with genes as rows and samples as columns. The matrix should be normalized (e.g., TPM, log2CPM, etc.).

TF.collection

Character. The source of the TF-target network. Options are "CollecTRI" (default), "Dorothea", or "ARACNE".

  • "CollecTRI" and "Dorothea" (confidence A and B) use prebuilt collections from OmnipathR. Each collection is cached in its own file, Results/TF_target_collection_<TF.collection>.csv, and reused on later calls.

  • "ARACNE" reads a tab-separated network file with Regulator and Target columns from input/ARACNE/<cancer.type>/network/network.txt (relative to the working directory). The mode of regulation of each edge is the sign of the Spearman correlation between TF and target expression.

min_targets_size

Integer. Minimum number of target genes per regulon (passed to decoupleR::decouple() as minsize). Default is 5.

universe

Optional. A user-specified data frame of TF-target interactions (columns source, target, mor). If not provided, the network is fetched based on TF.collection. Ignored when TF.collection = "ARACNE".

cancer.type

Optional character. TCGA cancer type abbreviation used to locate the ARACNe network (only used when TF.collection = "ARACNE"). If NULL, the network is auto-detected when only one network.txt exists under input/ARACNE/.

scale

Logical. If TRUE (default), z-score scales the TF activity matrix across samples.

return

Logical; if TRUE, saves matrix in Results/ folder. Default is TRUE.

file.name

Optional character suffix used when writing the TF activity matrix to disk.

Value

A data frame of inferred (and, if scale = TRUE, scaled) TF activity scores, with samples as rows and TFs as columns. Column names are made syntactically valid with make.names().

References

Badia-i-Mompel, P. et al. (2022). decoupleR: ensemble of computational methods to infer biological activities from omics data. Bioinformatics Advances, 2(1), vbac016. https://doi.org/10.1093/bioadv/vbac016

Tuerei, D., Korcsmaros, T., & Saez-Rodriguez, J. (2016). OmniPath: guidelines and gateway for literature-curated signaling pathway resources. Nature Methods, 13(12), 966-967. https://doi.org/10.1038/nmeth.4077

Garcia-Alonso, L. et al. (2019). Benchmark and integration of resources for the estimation of human transcription factor activities. Genome Research. https://doi.org/10.1101/gr.240663.118

Lachmann, A. et al. (2016). ARACNe-AP: gene network reverse engineering through adaptive partitioning inference of mutual information. Bioinformatics, 32(14), 2233-2235. https://doi.org/10.1093/bioinformatics/btw216

Margolin, A.A. et al. (2006). ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics, 7(Suppl 1), S7. https://doi.org/10.1186/1471-2105-7-S1-S7

Examples

if (FALSE) { # \dontrun{
# Downloads the CollecTRI network from OmniPath
data("counts.norm.tuto")
tfs_activity <- compute.TFs.activity(counts.norm.tuto)
} # }