MultiSpaceNet: Graph-based Joint Representation Learning for Paired Spatial Transcriptome-Proteome Data

Paired spatial assays now measure the transcriptome and the proteome on the same tissue section. Existing integration methods commit to a structural choice at the outset: a separate graph per modality, early fusion that folds the measured protein into the embedding so it can no longer be predicted, or intersection rules that discard most similarity edges. Each choice limits what one trained model can do afterwards.

We present MultiSpaceNet, a graph-based framework for joint representation learning from paired spatial transcriptomic and proteomic data. A section is represented as one cell graph over a shared node set, with spatial, transcriptomic and proteomic relations carried as typed edges and the two modality branches kept separate until a per-cell attention fusion. On five benchmark datasets, MultiSpaceNet outperforms nine published state-of-the-art methods in spatial domain identification (mean adjusted Rand index 0.472). Its leakage-free RNA-to-protein imputation matches or exceeds established methods for signal-bearing proteins, and it preserves biological structure across replicate sections better than all compared alternatives. A single trained model thus provides spatial domains, protein imputation, cross-section joint embedding and descriptive per-cell modality-dominance maps.

Source code is available at https://github.com/yongzhuangliulab/MultiSpaceNet and archived at Zenodo (DOI 10.5281/zenodo.22667390). The scripts that regenerate the reported tables and figures, together with their machine-readable result summaries, are included in the repository (directory resubmission/) and its Zenodo archive.

Supplementary data are available at Bioinformatics online.