GatorSC: multi-scale cell and gene graphs with mixture-of-experts fusion for single-cell transcriptomics.

Authors

Yuxi Liu, Zhenhao Zhang, Mufan Qiu, Song Wang, Flora D Salim, Jun Shen, Tianlong Chen, Imran Razzak, Fuyi Li, Jiang Bian

Published in

Briefings in bioinformatics. Volume 27. Issue 3. May 04, 2026.

Abstract

Single-cell RNA sequencing (scRNA-seq) enables high-resolution characterization of cellular heterogeneity, but its rich, complementary structure across cells and genes remains underexploited, especially in the presence of technical noise and sparsity. Effectively leveraging this multi-scale structure is essentially an information fusion problem that requires integrating heterogeneous graph-based views of cells and genes into robust low-dimensional representations. In this paper, we introduce GatorSC, a unified representation learning framework that models scRNA-seq data through multi-scale cell and gene graphs and fuses them with a mixture-of-experts architecture. GatorSC constructs a global cell-cell graph, a global gene-gene graph, and a local gene-gene graph derived from neighborhood-specific subgraphs, and learns graph neural network embeddings that are adaptively fused by a gating network. To learn noise-robust and structure-preserving embeddings without labels, we couple graph reconstruction and graph contrastive learning in a unified self-supervised objective applied to both cell- and gene-level graphs. We evaluate GatorSC on 19 publicly available scRNA-seq datasets covering diverse tissues, species, and sequencing platforms. Experiments showed that GatorSC consistently outperforms state-of-the-art deep generative, graph-based, and contrastive methods for cell clustering, gene expression imputation, and cell-type annotation. The learned embeddings are used for accurate trajectory inference, recovery of canonical marker gene programs, and cell-type-specific pathway signatures in an Alzheimer's disease single-nucleus dataset. GatorSC provides a flexible foundation for comprehensive single-cell transcriptomic analysis and can be readily extended to multi-omic and spatial modalities.

PMID:
42308421
Bibliographic data and abstract were imported from PubMed on 18 Jun 2026.

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