Differential cell signaling testing for cell-cell communication inference from single-cell data by dominoSignal.

Area of Science:

• Computational Biology
• Single-cell Analysis
• Systems Biology

Background:

• Ligand-receptor network inference algorithms are crucial for estimating cell-cell communication from single-cell data.
• Existing methods often lack statistical rigor for identifying differential signaling between conditions.
• The Domino algorithm previously integrated gene expression with transcription factor activity for cell communication inference.

Purpose of the Study:

• To develop and introduce dominoSignal, a software package that extends Domino's capabilities.
• To enable statistically rigorous testing of differential cellular signaling.
• To facilitate the analysis of cell-cell communication in response to various perturbations.

Main Methods:

• Development of the dominoSignal software incorporating the Differential Cell Signaling Test (DCST).
• Compilation of active signals into linkages across multiple subjects and testing condition-dependent signaling.
• Application of simulation studies to benchmark data requirements for accurate differential linkage identification.
• Utilized single-cell data from cancer studies to investigate effects of phenotypes and immunotherapy on tumor microenvironment communication.

Main Results:

• dominoSignal enables the compilation and statistical testing of active signaling linkages from multi-subject single-cell datasets.
• The software accommodates datasets with biological or bootstrapped replicates, crucial for datasets with few or pooled subjects.
• Demonstrated the utility of DCST in dominoSignal for inferring communication network changes in cancer and immunotherapy contexts.

Conclusions:

• dominoSignal provides a statistically robust framework for analyzing differential cell signaling.
• The software is broadly applicable across diverse biological systems to understand communication network alterations.
• Facilitates the interpretation of cell-cell communication changes induced by therapeutic or experimental interventions.