Clustering with Communication: A Variational Framework for Single Cell Representation Learning

TL;DR

This paper introduces CCCVAE, a variational autoencoder that integrates cell-cell communication signals into single-cell data representations, improving clustering accuracy by embedding biological signaling context.

Contribution

The paper presents a novel framework that incorporates intercellular communication into deep generative models for single-cell analysis, enhancing biological relevance of embeddings.

Findings

CCCVAE outperforms standard VAEs in clustering tasks.

Embedding communication signals improves biological interpretability.

The model captures both transcriptional and signaling information.

Abstract

Single-cell RNA sequencing (scRNA-seq) has revealed complex cellular heterogeneity, but recent studies emphasize that understanding biological function also requires modeling cell-cell communication (CCC), the signaling interactions mediated by ligand-receptor pairs that coordinate cellular behavior. Tools like CellChat have demonstrated that CCC plays a critical role in processes such as cell differentiation, tissue regeneration, and immune response, and that transcriptomic data inherently encodes rich information about intercellular signaling. We propose CCCVAE, a novel variational autoencoder framework that incorporates CCC signals into single-cell representation learning. By leveraging a communication-aware kernel derived from ligand-receptor interactions and a sparse Gaussian process, CCCVAE encodes biologically informed priors into the latent space. Unlike conventional VAEs that treat each cell independently, CCCVAE encourages latent embeddings to reflect both transcriptional similarity and intercellular signaling context. Empirical results across four scRNA-seq datasets show that CCCVAE improves clustering performance, achieving higher evaluation scores than standard VAE baselines. This work demonstrates the value of embedding biological priors into deep generative models for unsupervised single-cell analysis.