--- license: bsd-3-clause library_name: interscale tags: - spatial-transcriptomics - xenium - cell-cell-communication - graph-neural-network - transformer - single-cell --- # InterScale — 10x Xenium human ovarian adenocarcinoma (held-out-split model) Pre-trained [InterScale](https://github.com/theislab/interscale) model (Drummer, Jiménez *et al.*, bioRxiv 2026) for the 10x Xenium human ovarian adenocarcinoma section used in the cell–cell communication chapter of the single-cell best-practices book. It is the model trained in the tutorial notebook `notebooks/psls_ccc/interscale_ovarian.ipynb`. Loading it lets you skip training and go straight to the net-flow and gene-programme analyses. InterScale combines a **local** GCN over the spatial neighbour graph with a **global** transformer over all cells of a tissue window. Each component reconstructs masked expression through its own decoder (`dual_decoder: true`). The transformer's cell-by-cell attention is what the net-flow analysis reads as directed communication between cell types. ## Files | file | contents | | --- | --- | | `model.pt` | trained weights, InterScale save format (`{"model_state_dict": ...}`), 20 MB | | `config.yaml` | full resolved config the weights were trained with; only the two local paths are blanked | | `genes.tsv` | the 3,000 input genes **in model order**, with their Moran's I | | `metrics.json` | scores of this exact file on the held-out test windows | ## Loading Needs `interscale` from `main` at or after commit `c98a307`, the version it was trained with. ```python from huggingface_hub import snapshot_download import interscale from interscale.config import load_config d = snapshot_download("theislab/InterScale", allow_patterns="ovarian_xenium/heldout_split/*") d = f"{d}/ovarian_xenium/heldout_split" cfg = load_config(f"{d}/config.yaml") # `adata` must be prepared as described under "Input" below interscale.model.CombinedModel._setup_anndata( adata=adata, prediction_task="regression", layer_key="log1p_norm", sample_key_list=["sliding_window"], split_key=None, ) model = interscale.model.CombinedModel.load( d, adata, cfg, model_name="", local_component=True, global_component=True ) result = model.get_model_output(adata) # .obsm["_attn_matrix"], ["_local_emb"], ["_global_emb"], # .layers["_y_pred_local"], ["_y_pred_global"] ``` `load` raises if the config does not describe the checkpoint, so a model that loads is the trained model. It will not silently keep random weights. The recipe above was checked by reloading this folder and comparing all weights bit for bit. ## Input The model expects the tutorial's preprocessing. Section 2 of `interscale_ovarian.ipynb` does all of it: * **Expression:** `adata.layers["log1p_norm"]` = `log1p(normalize_total(counts))`. * **Genes:** exactly the 3,000 genes of `genes.tsv`, **in that order** (`adata = adata[:, genes].copy()`). They are the most spatially variable genes of the 4,447-gene panel by Moran's I (radius-30 µm graph, whole slide). * **Windows:** `adata.obs["sliding_window"]`, 600 µm non-overlapping tiles of the slide made with `interscale.pp.sliding_window`, with windows of fewer than 50 cells dropped. The model builds a radius-30 µm neighbour graph inside each window. * **Window size limit:** the largest window must have at most **3,167 cells**, the config's `max_seq_len`. For larger windows, raise `model.global_component.parameters.max_seq_len` in the config. A too-small value silently subsamples windows. * `adata.obsm["spatial"]` in µm. ## Training | | | | --- | --- | | data | one section, 400,600 cells, 199 windows (mean 2,013 cells) | | split | over **windows**, 70 / 15 / 15 → 139 train / 29 val / 31 test, seed 44 | | objective | node-level reconstruction, **cell masking at 30 %**, SmoothL1 on the masked cells | | architecture | 2-layer GCN (hidden 512, dropout 0.1) → 2-layer transformer (4 heads, FF 512, dropout 0) → linear decoders, latent width 256 | | optimisation | lr 0.003, weight decay 0.001, cosine schedule with 10-epoch warm-up, batch 2 windows, early stopping on val loss (stopped at epoch 242 of max 600) | | hardware | 1× NVIDIA H100 80 GB, ~17 min | The hyperparameters are the best of a 48-trial random sweep over masking strategy (cell 10/30/50 %, gene 25/50/75 %), latent width (32–256), GCN/transformer size, dropout, learning rate, weight decay and batch size. The best config was then re-trained at three seeds and was stable across them, with a spread under 0.01 in r. ## Evaluation Scored on the **31 held-out test windows** (65,804 cells), as the median over genes of the per-gene Pearson r. The masks are fixed (seed 2026), so other models can be compared on the same entries. | test condition | local decoder | global decoder | | --- | --- | --- | | 30 % of cells fully masked (the training task) | 0.163 | 0.165 | | 50 % of (cell, gene) entries masked | 0.165 | 0.167 | | no masking (what `get_model_output` returns) | 0.175 | 0.160 | ## Citation Drummer, F., Jiménez, S. *et al.* InterScale. bioRxiv (2026). Code: https://github.com/theislab/interscale