SpatialCCCbench: Standardized Metrics for the Systematic Evaluation of Spatial Cell-Cell Communication Methods

Abstract

Spatial transcriptomics (ST) enables transcriptome profiling with preserved spatial context, providing spatial dimensions that are essential for understanding complex intercellular signals in tissue architecture. ST-based CCC tools integrate spatial and molecular information to decipher intercellular interactions from a spatially informed perspective. Despite the rapid evolution of many CCC computational tools, a systematic assessment of their performance in handling ST-specific heterogeneity, utilizing spatial information efficiently, and robustness against technical or biological noise is still lacking. To address this gap, SpatialCCCbench incorporates classification accuracy, spatial signal features, robustness, and user-friendliness, aiming to guide the selection of optimal CCC inference tools across diverse spatial biology contexts. SpatialCCCbench systematically evaluates the scenario-specific applicability of ST-based CCC tools. It helps users select tools according to their analytical objectives and provides a practical benchmark for future method development. HighlightsO_LIEstablished a multi-dimensional benchmark suite to evaluate cell-cell communication (CCC) inference methods in spatial transcriptomics. C_LIO_LICharacterized the spatial patterns of CCC signals across diverse tissues using spatial autocorrelation and local diversity analysis. C_LIO_LISystematically assessed the robustness of CCC inference tools across six common experimental noise scenarios in spatial transcriptomics. C_LIO_LIIntegrated boundary-feature analysis, a mechanistically important component for biological interpretation, to uncover spatial preferences and algorithmic biases in CCC methods. C_LIO_LIProvided guidelines to assist in the selection of optimal CCC inference tools tailored to various spatial biology contexts. C_LI Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/724475v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@12bbc6aorg.highwire.dtl.DTLVardef@5eee6borg.highwire.dtl.DTLVardef@76d8f2org.highwire.dtl.DTLVardef@9d077e_HPS_FORMAT_FIGEXP M_FIG C_FIG