Table 3.

Summary of principle and tools for investigation of intercellular communication by single cell sequencing

Method	Tools	Platform	Characteristic
Differential combinations	CellTalker	R	1. Differential ligand–receptor pairs can be calculated. 2. Capture highly abundant ligand–receptor pairs via comparative analysis.
	iTALK	R
	PyMINEr	Python
Expression permutation	CellChat	R and Web	1. Discard random noise results via permutation test. 2. Cluster-to-cluster communication is inferred.
	CellPhoneDB	Python and Web
	Giotto	R
	ICELLNET	R
	SingleCellSignalR	R
	ProxmID	Software
	CSOmap	Matlab
	Cell2Cell	Python
	MISTY	R
	stLearn	Python
	SVCA	R and Python
Graph or network	CCCExplorer	Software	1. With a prior model, the inference is beyond ligand–receptor interactions and incorporates intracellular signaling. 2. Inference of cell-to-cell communication is possible. 3. Signaling pathway information can also be used.
	NicheNet	R
	SoptSC	Matlab and R
	SpaOTsc	Python
	COMUNET	R
	NATMI	Python
Tensor based	scTensor	R	Detect many-to-many CCC involving multiple cell clusters rather than one-to-one CCC.