Predict cell-type-specific enhancer-driven gene regulatory networks (eGRNs)

Source: R/run_stream.R

Transcription factors (TFs) interact with chromatin regions (herein we call them enhancers), to regulate the downstream target genes. Joint profiling of scRNA-seq and scATAC-seq shed light upon gene expression and chromatin accessibility in each cell, providing a great opportunity to inspect the underlying gene regulatory mechanisms in different cell types. Enhancer-driven gene regulatory networks (eGRNs) are gene regulatory networks (GRNs) in which TFs regulate their target genes via binding accessible enhancers in a cell type/state/subpopulation. This function takes as input a Seurat object and a list of eRegulons, and then outputs cell-type-specific eGRNs.

get_cts_en_GRNs(
  obj = NULL,
  celltype = "seurat_clusters",
  en.regs = NULL,
  peak.assay = "ATAC",
  rna.dims = 50,
  atac.dims = 50,
  padj.cutoff = 0.05,
  out.dir = "./"
)

Arguments

obj

An Seurat object.

celltype

The metadata column indicating the cell types or clusters, "seurat_clusters" by default.

en.regs

A list of cell-type-specific eRegulons, each of which contains the following attributes:

  • terminal: The IRIS-FGM block used to predict the eRegulon.

  • Tier: The tier of the TF-enhancer relations: 1 represents JASPAR annotations; 2 denotes motif scanning.

  • TF: The TF of the eRegulon.

  • genes: Genes of the eRegulon.

  • peaks: Enhancers of the eRegulon.

  • cells: Cells where the eRegulon is active.

  • atac.ratio: The ratio of cells where the eRegulon enhancers are accessible against cells in which the eRegulon genes are expressed.

  • score: The eRegulon score.

  • weight: The eRegulon weight.

  • links: The enhancer-gene relations saved in GRanges object.

  • seed: The seed to obtain the eRegulon.

peak.assay

The chromatin accessibility assay, "ATAC" by default.

rna.dims

The number of dimensions for RNA dimension reduction, 50 by default.

atac.dims

The number of dimensions for ATAC dimension reduction, 50 by default.

padj.cutoff

The cutoff of adjusted p-value of hyper-geometric test, 0.05 by default.

out.dir

The directory to save the intermediate results or final results, "./" by default.

Value

Returns a list of eGRNs in each cell type saved in GRanges object, the name of each of which is cell type, and the GRanges object contains metadata columns "gene" and "TF".

#' @references Li, Y., Ma, A., Wang, Y., Wang, C., Chen, S., Fu, H., Liu, B. and Ma, Q., 2022. Enhancer-driven gene regulatory networks inference from single-cell RNA-seq and ATAC-seq data. bioRxiv, pp.2022-12.