Graph-structured joint-embedding prediction for single-cell transcriptomics
cs.LG
Submitted: 2026-08-06
Updated: 2026-10-27
Comments: 34 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 BioM-JEPA checkpoint will be released via GitHub
Code: https://github.com/sky-Yongjie-Xu/2026-CellBench
License: http://creativecommons.org/licenses/by/4.0/
The gist: Single-cell transcriptomes are sparse observations of coordinated biological programmes, yet most self-supervised models learn by reconstructing individual genes.
Terminology
Abstract
Single-cell transcriptomes are sparse observations of coordinated biological programmes, yet most self-supervised models learn by reconstructing individual genes. Here we present BioM-JEPA, a joint-embedding predictive architecture that instead predicts aggregate representations of graph-connected gene blocks defined by protein-association and corpus-derived coexpression evidence. A student network infers each target-block representation from the remaining genes in a cell, while a slowly updated teacher supplies the corresponding target from the full observed gene set. Under the reported extraction procedure, block-level prediction produced embeddings with higher effective rank and weaker association with detected-gene depth in the tested diagnostics than token-prediction, random-block and reconstruction controls. Across CellBench tasks, frozen BioM-JEPA embeddings retained expression, pathway and neighbourhood information and achieved the lowest aggregate perturbation-response error among the evaluated models. Representation diagnostics were also consistent with canonical pancreatic programmes and compositional relationships between genetic perturbations. Linear attention avoids constructing a quadratic gene-by-gene attention matrix; in a matched one-epoch hPancreas experiment at batch size 8, BioM-JEPA provided 5.75-fold higher fine-tuning throughput and 3.76-fold higher held-out embedding throughput than scFoundation. Together, these results support graph-connected gene blocks as useful prediction units for JEPA-style representation learning in single-cell biology.
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