---
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 (full-slide model, no held-out split)

Pre-trained [InterScale](https://github.com/theislab/interscale) model (Drummer, Jiménez *et al.*,
bioRxiv 2026) for the 10x Xenium human ovarian adenocarcinoma section of the cell–cell communication
chapter of the single-cell best-practices book, trained on **every window of the section**. It is
the sibling of [`../heldout_split`](../heldout_split), which uses the same architecture and
hyperparameters but holds out 30 % of the windows. Use this one to *read out* the tissue — attention
flows, gene programmes — where holding out windows would only discard cells; use `heldout_split`
when you need generalisation numbers. Trained in `notebooks/psls_ccc/interscale_ovarian_train_full_slide.ipynb`,
interpreted in `interscale_ovarian_full_slide_interpretation.ipynb`.

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 (`{"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` | in-sample scores of this exact file on all windows (there is no held-out data) |

## 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/no_heldout_split/*")
d = f"{d}/ovarian_xenium/no_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
)
model.module.eval()  # a loaded model starts in training mode, where dropout makes every run differ
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 | **none** — all 199 windows are training data (`train_size` 1.0, `val_size` 0.0) |
| 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, **fixed 250 epochs, no early stopping** (250 ≈ where the held-out-split model stopped on its own: 242; 148–307 over 3 seeds) |
| hardware | 1× NVIDIA H100 80 GB |

Hyperparameters are those of `heldout_split` (the best of a 48-trial random sweep), unchanged.
Lightning needs a validation loader, so it received copies of the training windows with their own
masks; that is a convergence monitor, not a held-out score.

## Evaluation

There is no held-out data, so every number below is **in-sample**. They are shown next to the
`heldout_split` model scored on the **same 199 windows with the same fixed masks** (seed 2026), as
the median over genes of the per-gene Pearson r:

| condition | this model, local / global | `heldout_split`, local / global |
| --- | --- | --- |
| 30 % of cells fully masked (the training task) | 0.182 / 0.204 | 0.178 / 0.184 |
| 50 % of (cell, gene) entries masked | 0.180 / 0.115 | 0.178 / 0.184 |

On the task it was trained for, the model is slightly better, as expected from more training data
and a longer schedule on the cells it is scored on. Its **global decoder generalises worse to
gene-level masking** (0.115 vs 0.184): trained longer on whole-cell masking only, it has specialised
more narrowly. The attention and gene-rank read-outs use the unmasked pass and are not directly
affected, but prefer `heldout_split` if you reconstruct partially observed cells.

## Limitations

* **No generalisation estimate.** Every cell was seen in training; use `heldout_split` for
  out-of-sample numbers.
* **One tissue section.** Like `heldout_split`, the model describes this section, not ovarian cancer
  in general.
* Attention-based net flow is a model read-out, not a measurement of ligand–receptor signalling.

## Citation


Drummer, F., Jiménez, S. *et al.* InterScale. bioRxiv (2026). Code:
https://github.com/theislab/interscale