Graph-structured joint-embedding prediction for single-cell transcriptomics

Abstract

Single-cell transcriptomes are sparse, unordered measurements of coordinated biological activity, yet many self-supervised models define their learning target at the level of individual genes or reconstructed expression values. Here we introduce GB-JEPA, a joint-embedding predictive architecture in which graph-connected gene blocks form the latent prediction units. A student encoder observes the genes outside each target block, whereas an exponential-moving-average teacher represents the full observed gene set. Teacher states are aggregated within a block before the prediction error is evaluated, converting thousands of sparse gene-level targets into a small collection of intermediate-scale latent targets. The graph therefore serves not only as prior information, but also as a mechanism for controlling the structure, scale and predictability of self-supervision. We evaluate the resulting frozen cell representations through objective diagnostics, cell-state annotation, continuous-expression and pathway probes, perturbation-response prediction, computational measurements and direct biological interrogation. This study presents a graph-structured route for adapting JEPA learning to molecular observations and a general framework for designing prediction units from relationships native to a biological modality.

arXiv comment33 pages, 6 figures, and 13 supplementary tables (Tables S1-S13); includes Supplementary Information with detailed training and evaluation protocols. Numerical source data for all figures are provided as ancillary files; training code and the GB-JEPA checkpoint will be released via GitHub