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Introduction

SpaTalk is a computational framework for inferring spatially resolved cell-cell communications (CCIs) from spatial transcriptomics (ST) data. Published in Nature Communications (2022), SpaTalk integrates graph network modeling and knowledge graph approaches to reconstruct ligand-receptor-target signaling networks between spatially proximal cells.

Citation

Shao, X., Li, C., Yang, H., et al. Knowledge-graph-based cell-cell communication inference for spatially resolved transcriptomic data with SpaTalk. Nature Communications 13, 4429 (2022). https://doi.org/10.1038/s41467-022-32111-8

Key Features

  • Cell-type deconvolution for spot-based ST data using NNLM
  • Spatial mapping between scRNA-seq and ST data
  • Knowledge graph-based ligand-receptor-target pathway inference
  • Permutation-based statistical validation
  • Support for single-cell and spot-based ST platforms

Installation

# From R-universe (recommended)
install.packages("SpaTalk", repos = "https://zaoqu-liu.r-universe.dev")

# From GitHub
devtools::install_github("Zaoqu-Liu/SpaTalk")

Quick Start with STARmap Data

This tutorial uses the built-in STARmap mouse visual cortex data.

Step 1: Load Package and Data

library(SpaTalk)

# Load built-in demo data
load(system.file("extdata", "starmap_data.rda", package = "SpaTalk"))
load(system.file("extdata", "starmap_meta.rda", package = "SpaTalk"))

# Load curated databases
data(lrpairs)
data(pathways)

cat("Expression matrix:", nrow(starmap_data), "genes x", ncol(starmap_data), "cells\n")
#> Expression matrix: 996 genes x 930 cells
cat("Metadata:", nrow(starmap_meta), "cells\n")
#> Metadata: 930 cells
cat("Cell types:", paste(unique(starmap_meta$celltype), collapse = ", "), "\n")
#> Cell types: eL2_3, eL6, Astro, PVALB, Endo, VIP, SST, Smc, eL4, Micro, Oligo, eL5, Reln, HPC

Step 2: Create SpaTalk Object

# Prepare spatial metadata
st_meta <- data.frame(
  cell = starmap_meta$cell,
  x = starmap_meta$x,
  y = starmap_meta$y
)

# Create SpaTalk object (single-cell resolution data)
obj <- createSpaTalk(
  st_data = starmap_data,
  st_meta = st_meta,
  species = "Mouse",
  if_st_is_sc = TRUE,
  spot_max_cell = 1,
  celltype = starmap_meta$celltype
)

obj
#> An object of class SpaTalk 
#> 996 genes across 930 single-cells (0 lrpair)

Step 3: Visualize Spatial Distribution

plot_st_celltype_all(obj, size = 1.2)
Spatial distribution of all cell types

Spatial distribution of all cell types

Step 4: Filter LR-Pathway Pairs

# Find LR pairs with downstream pathway targets
obj <- find_lr_path(
  object = obj,
  lrpairs = lrpairs,
  pathways = pathways,
  if_doParallel = FALSE
)
#> Checking input data 
#> Begin to filter lrpairs and pathways 
#> ***Done*** 
#> 

cat("Filtered LR pairs:", nrow(obj@lr_path$lrpairs), "\n")
#> Filtered LR pairs: 6

Step 5: Infer Cell-Cell Communications

# Infer CCIs between specific cell types
obj <- dec_cci(
  object = obj,
  celltype_sender = "eL6",
  celltype_receiver = "PVALB",
  if_doParallel = FALSE
)
#> Begin to find LR pairs 
#> 

# View results
if(nrow(obj@lrpair) > 0) {
  cat("Found", nrow(obj@lrpair), "significant LR pairs:\n")
  print(obj@lrpair[, c("ligand", "receptor", "lr_co_ratio", "lr_co_ratio_pvalue", "score")])
}
#> Found 1 significant LR pairs:
#>   ligand receptor lr_co_ratio lr_co_ratio_pvalue     score
#> 5  Inhba   Acvr1c   0.1666667              0.002 0.8541642

Step 6: Visualize Results

Cell-Cell Distance Distribution

plot_ccdist(
  object = obj,
  celltype_sender = "eL6",
  celltype_receiver = "PVALB"
)
Distance distribution between eL6 and PVALB cells

Distance distribution between eL6 and PVALB cells

LR Pair Spatial Distribution

if(nrow(obj@lrpair) > 0) {
  lr <- obj@lrpair[1, ]
  plot_lrpair(
    object = obj,
    ligand = lr$ligand,
    receptor = lr$receptor,
    celltype_sender = "eL6",
    celltype_receiver = "PVALB",
    size = 1.2
  )
}
Spatial distribution of ligand-receptor interactions

Spatial distribution of ligand-receptor interactions

Next Steps

  • See the Algorithm vignette for methodological details
  • See the Visualization vignette for all plotting options
  • See the Advanced Usage vignette for custom databases and parallel processing
  • See the Platforms vignette for platform-specific workflows

Session Info

sessionInfo()
#> R version 4.4.0 (2024-04-24)
#> Platform: aarch64-apple-darwin20
#> Running under: macOS 15.6.1
#> 
#> Matrix products: default
#> BLAS:   /Library/Frameworks/R.framework/Versions/4.4-arm64/Resources/lib/libRblas.0.dylib 
#> LAPACK: /Library/Frameworks/R.framework/Versions/4.4-arm64/Resources/lib/libRlapack.dylib;  LAPACK version 3.12.0
#> 
#> locale:
#> [1] C
#> 
#> time zone: Asia/Shanghai
#> tzcode source: internal
#> 
#> attached base packages:
#> [1] parallel  stats     graphics  grDevices utils     datasets  methods  
#> [8] base     
#> 
#> other attached packages:
#> [1] SpaTalk_2.0.0     doParallel_1.0.17 iterators_1.0.14  foreach_1.5.2    
#> [5] ggalluvial_0.12.5 ggplot2_4.0.1    
#> 
#> loaded via a namespace (and not attached):
#>   [1] RColorBrewer_1.1-3     jsonlite_2.0.0         magrittr_2.0.4        
#>   [4] spatstat.utils_3.2-1   farver_2.1.2           rmarkdown_2.30        
#>   [7] fs_1.6.6               ragg_1.5.0             vctrs_0.7.0           
#>  [10] ROCR_1.0-11            spatstat.explore_3.6-0 rstatix_0.7.3         
#>  [13] htmltools_0.5.9        progress_1.2.3         broom_1.0.11          
#>  [16] Formula_1.2-5          sass_0.4.10            sctransform_0.4.3     
#>  [19] parallelly_1.46.1      KernSmooth_2.23-26     bslib_0.9.0           
#>  [22] htmlwidgets_1.6.4      desc_1.4.3             ica_1.0-3             
#>  [25] plyr_1.8.9             plotly_4.11.0          zoo_1.8-15            
#>  [28] cachem_1.1.0           igraph_2.2.1           mime_0.13             
#>  [31] lifecycle_1.0.5        pkgconfig_2.0.3        Matrix_1.7-4          
#>  [34] R6_2.6.1               fastmap_1.2.0          fitdistrplus_1.2-4    
#>  [37] future_1.69.0          shiny_1.12.1           digest_0.6.39         
#>  [40] patchwork_1.3.2        Seurat_4.4.0           tensor_1.5.1          
#>  [43] irlba_2.3.5.1          textshaping_1.0.4      ggpubr_0.6.2          
#>  [46] labeling_0.4.3         progressr_0.18.0       spatstat.sparse_3.1-0 
#>  [49] httr_1.4.7             polyclip_1.10-7        abind_1.4-8           
#>  [52] compiler_4.4.0         withr_3.0.2            backports_1.5.0       
#>  [55] S7_0.2.1               carData_3.0-5          ggforce_0.5.0         
#>  [58] ggsignif_0.6.4         MASS_7.3-65            rappdirs_0.3.4        
#>  [61] ggsci_4.2.0            tools_4.4.0            lmtest_0.9-40         
#>  [64] otel_0.2.0             scatterpie_0.2.6       httpuv_1.6.16         
#>  [67] future.apply_1.20.1    goftest_1.2-3          glue_1.8.0            
#>  [70] nlme_3.1-168           promises_1.5.0         grid_4.4.0            
#>  [73] Rtsne_0.17             cluster_2.1.8.1        reshape2_1.4.5        
#>  [76] generics_0.1.4         gtable_0.3.6           spatstat.data_3.1-9   
#>  [79] tzdb_0.5.0             tidyr_1.3.2            data.table_1.18.0     
#>  [82] hms_1.1.4              car_3.1-3              sp_2.2-0              
#>  [85] spatstat.geom_3.6-1    RcppAnnoy_0.0.23       ggrepel_0.9.6         
#>  [88] RANN_2.6.2             pillar_1.11.1          stringr_1.6.0         
#>  [91] yulab.utils_0.2.3      ggExtra_0.11.0         later_1.4.5           
#>  [94] splines_4.4.0          tweenr_2.0.3           dplyr_1.1.4           
#>  [97] lattice_0.22-7         survival_3.8-3         deldir_2.0-4          
#> [100] tidyselect_1.2.1       miniUI_0.1.2           pbapply_1.7-4         
#> [103] knitr_1.51             gridExtra_2.3          scattermore_1.2       
#> [106] xfun_0.56              matrixStats_1.5.0      pheatmap_1.0.13       
#> [109] stringi_1.8.7          ggfun_0.2.0            lazyeval_0.2.2        
#> [112] yaml_2.3.12            evaluate_1.0.5         codetools_0.2-20      
#> [115] tibble_3.3.1           cli_3.6.5              uwot_0.2.4            
#> [118] xtable_1.8-4           reticulate_1.44.1      systemfonts_1.3.1     
#> [121] jquerylib_0.1.4        dichromat_2.0-0.1      Rcpp_1.1.1            
#> [124] globals_0.18.0         spatstat.random_3.4-3  png_0.1-8             
#> [127] spatstat.univar_3.1-6  readr_2.1.6            pkgdown_2.1.3         
#> [130] NNLM_0.4.4             prettyunits_1.2.0      listenv_0.10.0        
#> [133] viridisLite_0.4.2      scales_1.4.0           ggridges_0.5.7        
#> [136] SeuratObject_4.1.4     leiden_0.4.3.1         purrr_1.2.1           
#> [139] crayon_1.5.3           rlang_1.1.7            cowplot_1.2.0