Zedong Hu

Mark Eastwood, Thomas McKee, Zedong Hu et al.

Separating the contributions of individual chromogenic stains in RGB histology whole slide images (WSIs) is essential for stain normalization, quantitative assessment of marker expression, and cell-level readouts in immunohistochemistry (IHC). Classical Beer-Lambert (BL) color deconvolution is well-established for two- or three-stain settings, but becomes under-determined and unstable for multiplex IHC (mIHC) with K>3 chromogens. We present a simple, data-driven encoder-decoder architecture that learns cohort-specific stain characteristics for mIHC RGB WSIs and yields crisp, well-separated per-stain concentration maps. The encoder is a compact U-Net that predicts K nonnegative concentration channels; the decoder is a differentiable BL forward model with a learnable stain matrix initialized from typical chromogen hues. Training is unsupervised with a perceptual reconstruction objective augmented by loss terms that discourage unnecessary stain mixing. On a colorectal mIHC panel comprising 5 stains (H, CDX2, MUC2, MUC5, CD8) we show excellent RGB reconstruction, and significantly reduced inter-channel bleed-through compared with matrix-based deconvolution. Code and model are available at https://github.com/measty/StainQuant.git.

Piotr Keller, Mark Eastwood, Zedong Hu et al.

Routine histology contains rich prognostic information in stage II/III colorectal cancer, much of which is embedded in complex spatial tissue organisation. We present INSIGHT, a graph neural network that predicts survival directly from routine histology images. Trained and cross-validated on TCGA (n=342) and SURGEN (n=336), INSIGHT produces patient-level spatially resolved risk scores. Large independent validation showed superior prognostic performance compared with pTNM staging (C-index 0.68-0.69 vs 0.44-0.58). INSIGHT spatial risk maps recapitulated canonical prognostic histopathology and identified nuclear solidity and circularity as quantitative risk correlates. Integrating spatial risk with data-driven spatial transcriptomic signatures, spatial proteomics, bulk RNA-seq, and single-cell references revealed an epithelium-immune risk manifold capturing epithelial dedifferentiation and fetal programs, myeloid-driven stromal states including $\mathrm{SPP1}^{+}$ macrophages and $\mathrm{LAMP3}^{+}$ dendritic cells, and adaptive immune dysfunction. This analysis exposed patient-specific epithelial heterogeneity, stratification within MSI-High tumours, and high-risk routes of CDX2/HNF4A loss and CEACAM5/6-associated proliferative programs, highlighting coordinated therapeutic vulnerabilities.