CreateConnectome

Creates a connectomic edgelist from a Seurat object. The connectome represents all possible ligand-receptor interactions between cell populations, weighted by expression levels and statistical significance.

Usage

CreateConnectome(
  object,
  LR.database = "fantom5",
  species = NULL,
  include.putative = TRUE,
  include.rejected = FALSE,
  p.values = TRUE,
  max.cells.per.ident = NULL,
  min.cells.per.ident = NULL,
  weight.definition.norm = "product",
  weight.definition.scale = "mean",
  custom.list = NULL,
  calculate.DOR = FALSE,
  assay = "RNA",
  parallel = FALSE,
  n.cores = NULL,
  ...
)

Arguments

object

A Seurat object with normalized and scaled data

LR.database

Ligand-receptor database to use. Either 'fantom5' (default) or 'custom'. If 'custom', provide a dataframe via custom.list parameter.

species

Species for FANTOM5 database. Required if LR.database = 'fantom5'. Options: 'human', 'mouse', 'rat', or 'pig'

include.putative

Include putative ligand-receptor pairs from FANTOM5. Default TRUE.

include.rejected

Include pairs labeled "EXCLUDED" in FANTOM5. Default FALSE.

p.values

Calculate Wilcoxon Rank Sum test p-values. Default TRUE. Set to FALSE for faster computation when statistical testing is not needed.

max.cells.per.ident

Maximum cells per identity for downsampling. Default NULL (no downsampling). Useful for large datasets.

min.cells.per.ident

Minimum cells required per identity. Default NULL. Clusters below this threshold are excluded from analysis.

weight.definition.norm

Method for edge weight from normalized data. Options: 'sum', 'mean', or 'product' (default).

weight.definition.scale

Method for edge weight from scaled data. Options: 'sum', 'mean' (default), or 'product'.

custom.list

Dataframe with custom ligand-receptor pairs. Required columns: ligand (col 1), receptor (col 2), mode/category (col 3).

calculate.DOR

Calculate log-normalized Diagnostic Odds Ratio. Default FALSE.

assay

Seurat assay to use. Default 'RNA'. Also accepts 'SCT'.

parallel

Use parallel processing for p-value calculations. Default FALSE.

n.cores

Number of cores for parallel processing. Default: detectCores() - 1

...

Additional arguments passed to internal functions

Value

A data.frame containing the connectomic edgelist with columns: source, target, ligand, receptor, pair, mode, expression values, z-scores, percent expressing, edge weights, and optionally p-values and DOR.

Details

The function calculates edge weights using the formula specified by weight.definition.norm and weight.definition.scale parameters:

• 'product': ligand * receptor (captures co-expression)

• 'sum': ligand + receptor (additive contribution)

• 'mean': (ligand + receptor) / 2 (average contribution)

Examples

if (FALSE) { # \dontrun{
# Basic usage
connectome <- CreateConnectome(seurat_obj, species = "human")

# Without p-value calculation (faster)
connectome <- CreateConnectome(seurat_obj, species = "human", p.values = FALSE)

# With custom ligand-receptor list
my_lr <- data.frame(ligand = c("IL6", "TNF"), receptor = c("IL6R", "TNFRSF1A"),
                    mode = c("cytokine", "cytokine"))
connectome <- CreateConnectome(seurat_obj, LR.database = "custom", custom.list = my_lr)
} # }