Multi-Species Analysis

# Get homology mapping from mouse to human
mapping <- GetHomologyMapping(from = "mouse", to = "human")
head(mapping)
#>    from_symbol to_symbol
#>         <char>    <char>
#> 1:       Acadm     ACADM
#> 2:      Acadvl    ACADVL
#> 3:       Acat1     ACAT1
#> 4:       Acvr1     ACVR1
#> 5:        Sgca      SGCA
#> 6:        Adsl      ADSL
cat("\nTotal mappings:", nrow(mapping), "\n")
#> 
#> Total mappings: 16766

# Example mouse genes
mouse_genes <- c("Cd4", "Cd8a", "Ptprc", "Itgam", "Cd19")

# Convert to human symbols
human_genes <- ConvertGeneSymbols(mouse_genes, from = "mouse", to = "human")
print(data.frame(mouse = mouse_genes, human = human_genes))
#>       mouse human
#> Cd4     Cd4   CD4
#> Cd8a   Cd8a  CD8A
#> Ptprc Ptprc PTPRC
#> Itgam Itgam ITGAM
#> Cd19   Cd19  CD19

set.seed(123)

# Simulate mouse single-cell data
n_genes <- 200
n_cells <- 300

# Create expression matrix with mouse gene names
expr <- matrix(0, nrow = n_genes, ncol = n_cells)
expressed <- sample(length(expr), size = length(expr) * 0.25)
expr[expressed] <- abs(rnorm(length(expressed), mean = 2, sd = 1))

# Get mouse LR pairs
lr_db <- GetLRDatabase("lrc2p")
mouse_mapping <- GetHomologyMapping("human", "mouse")

# Map some human ligands/receptors to mouse
mouse_ligands <- mouse_mapping$to_symbol[match(lr_db$ligand[1:30], mouse_mapping$from_symbol)]
mouse_receptors <- mouse_mapping$to_symbol[match(lr_db$receptor[1:30], mouse_mapping$from_symbol)]

# Remove NAs
mouse_ligands <- na.omit(mouse_ligands)
mouse_receptors <- na.omit(mouse_receptors)

# Set gene names
gene_names <- c(as.character(mouse_ligands[1:20]), 
                as.character(mouse_receptors[1:20]),
                paste0("MouseGene", 41:n_genes))
rownames(expr) <- gene_names
colnames(expr) <- paste0("Cell", 1:n_cells)

# Create annotation
clusters <- sample(c("T_cells", "B_cells", "Macrophages", "Fibroblasts"), 
                   n_cells, replace = TRUE)
annotation <- data.frame(
  cell = colnames(expr),
  cluster = clusters
)

# Run analysis specifying mouse
result <- ExtractEdges(
  expression = Matrix::Matrix(expr, sparse = TRUE),
  annotation = annotation,
  species = "mouse",  # Specify species
  database = "lrc2p",
  min_pct = 0.05
)

print(result)

# Human analysis
human_result <- ExtractEdges(
  expression = human_expr,
  annotation = human_ann,
  species = "human",
  database = "lrc2p"
)

# Mouse analysis (genes auto-converted)
mouse_result <- ExtractEdges(
  expression = mouse_expr,
  annotation = mouse_ann,
  species = "mouse",
  database = "lrc2p"
)

# Compare conserved interactions
human_pairs <- paste(human_result$edges$ligand, 
                     human_result$edges$receptor, sep = "-")
mouse_pairs <- paste(mouse_result$edges$ligand, 
                     mouse_result$edges$receptor, sep = "-")

conserved <- intersect(human_pairs, mouse_pairs)
cat("Conserved LR interactions:", length(conserved), "\n")

# Convert Ensembl IDs to symbols
ensembl_ids <- c("ENSG00000153563", "ENSG00000010610")
symbols <- ConvertGeneIDs(ensembl_ids, from = "ensembl", to = "symbol", species = "human")

# Check for duplicated mappings
mapping <- GetHomologyMapping("mouse", "human")
dup_genes <- mapping$from_symbol[duplicated(mapping$from_symbol)]
cat("Genes with multiple human orthologs:", length(unique(dup_genes)), "\n")
#> Genes with multiple human orthologs: 0

# Example: genes without orthologs
all_mouse_genes <- c("Actb", "Gapdh", "NoOrtholog123")
converted <- ConvertGeneSymbols(all_mouse_genes, "mouse", "human")
print(data.frame(mouse = all_mouse_genes, human = converted))
#>                       mouse human
#> Actb                   Actb  ACTB
#> Gapdh                 Gapdh GAPDH
#> NoOrtholog123 NoOrtholog123  <NA>

# Check ortholog mapping rate
mapping <- GetHomologyMapping("mouse", "human")
lr_db <- GetLRDatabase("lrc2p")

# How many ligands can be mapped?
ligand_mapped <- sum(lr_db$ligand %in% mapping$from_symbol)
receptor_mapped <- sum(lr_db$receptor %in% mapping$from_symbol)

cat("Ligands mappable to mouse:", ligand_mapped, "/", length(unique(lr_db$ligand)), "\n")
#> Ligands mappable to mouse: 27 / 829
cat("Receptors mappable to mouse:", receptor_mapped, "/", length(unique(lr_db$receptor)), "\n")
#> Receptors mappable to mouse: 3 / 690