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Attribution, Provenance & Design Notes

Licensing note: SpatialTranscriptFormer is released under the Apache License 2.0 (see LICENSE and NOTICE). This document is descriptive — it records design provenance and attributions for readers and reviewers. It does not itself grant or reserve any rights.

Provenance

This implementation is original work. The multimodal interaction framing — treating learnable biological-pathway tokens as a bottleneck that cross-attends to histology patch tokens — was conceptually inspired by SURVPATH (Jaume et al., 2024). No SURVPATH source code is used, copied, or adapted here; the model, losses, data pipeline, and training code were written from scratch for the spatial-transcriptomics pathway-activity task.

Design contributions

The notable design choices of this project (described for readers/reviewers, not as legal claims):

  • Pathway-exclusive prediction. The model predicts pre-computed spatial pathway-activity targets directly, with no intermediate gene-reconstruction step. Targets are computed offline (QC → CP10k normalisation → mean pathway aggregation; see PATHWAY_MAPPING.md), decoupling biological-knowledge integration from training and removing the circular auxiliary-loss dependency used in earlier prototypes.

  • Dot-product + Softplus scoring head. Per-spot pathway scores are softplus(scale · (patch · pathwayᵀ / √d) + bias), with learnable per-pathway scale and bias. Softplus yields non-negative scores matching the mean-log1p-CP10k targets; the √d scaling keeps affinities well-conditioned (as in scaled dot-product attention). This is not cosine similarity.

  • Configurable quad-flow interaction masking. Attention between pathway (P) and histology (H) tokens is selectable per quadrant (p2p, p2h, h2p, h2h), enabling ablations and the "pathway bottleneck" variant (block h2h so all inter-patch information must flow through named pathways).

  • Slide-stationary spatial positional encoding. Patch tokens receive a learned 2-D encoding of centred/standardised coordinates, so the model learns spatially-varying pathway maps rather than slide-level averages.

  • Moran's I as diagnostic + collapse detector. Spatial autocorrelation is used to curate targets and to detect representation collapse during validation (correlation of predicted vs. ground-truth per-pathway Moran's I), rather than as a loss term. See spatial_stats.py.

Third-party attributions

See NOTICE for the licenses and attribution requirements of the datasets, gene sets, and foundation-model backbones this framework uses at runtime (HEST-1k, MSigDB Hallmarks, CTransPath / Phikon / GigaPath / Hibou, …).

Citing

If you use this work in academic research, please cite this repository and its author, Benjamin Isaac Wilson, alongside the relevant third-party works listed in NOTICE.