Identify cell-type-specific enhancer regulons (eRegulons)

Source: R/run_stream.R

Enhancer regulons (eRegulons) are active in various cell subpopulations. Some of them may be enriched in one or more cell types. The successful identification of eRegulons at the single-cell level can improve the detection of heterogeneous transcriptional regulatory mechanisms across various cell types and allows for reliable constructions of global gene regulatory networks encoded in complex diseases. Hence, it is critical to study cell-type-specific eRegulons. eRegulons specific to a cell type are called cell-type-specific eRegulons. This function takes as input a Seurat object (composed of scRNA-seq and scATAC-seq) and cell-type-specific enhancer-drive gene regulatory networks (eGRNs) and then identify the cell-type-specific eRegulons in each cell type/cluster.

get_cts_en_regs(
  obj = NULL,
  peak.assay = "ATAC",
  de.genes = NULL,
  celltype = "celltype",
  cts.en.grns = NULL,
  accessibility = FALSE,
  out.dir = "./",
  min.pct = 0.25,
  logfc.threshold = 0.25,
  padj.cutoff = 0.05
)

Arguments

obj

An Seurat object.

peak.assay

The chromatin accessibility assay, "ATAC" by default.

de.genes

A list of differentially expressed genes (DEGs).

celltype

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

cts.en.grns

Cell-type-specific eGRNs saved in GRanges object, the name of each of which is cell type, and the GRanges object contains metadata columns "gene" and "TF".

accessibility

Whether perform differential accessibility analysis, FALSE by default.

out.dir

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

padj.cutoff

The cutoff of adjusted p-values of differential expression, 0.05 by default.

Value

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

  • TF: The TF of the cell-type-specific eRegulons.

  • genes: Genes of the cell-type-specific eRegulons.

  • enhancers: Enhancers of the cell-type-specific eRegulons.

  • cells: Cells where the celltype.

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

  • celltype: The celltype of the cell-type-specific eRegulons.

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.