ProteinPNet: Prototypical Part Networks for Concept Learning in Spatial Proteomics

Fuente: arXiv
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Main Authors: McConnell, Louis, Sun, Jieran, Maffei, Theo, Gottardo, Raphael, Rapsomaniki, Marianna
Format: Preprint
Published: 2025
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author McConnell, Louis
Sun, Jieran
Maffei, Theo
Gottardo, Raphael
Rapsomaniki, Marianna
author_facet McConnell, Louis
Sun, Jieran
Maffei, Theo
Gottardo, Raphael
Rapsomaniki, Marianna
contents Understanding the spatial architecture of the tumor microenvironment (TME) is critical to advance precision oncology. We present ProteinPNet, a novel framework based on prototypical part networks that discovers TME motifs from spatial proteomics data. Unlike traditional post-hoc explanability models, ProteinPNet directly learns discriminative, interpretable, faithful spatial prototypes through supervised training. We validate our approach on synthetic datasets with ground truth motifs, and further test it on a real-world lung cancer spatial proteomics dataset. ProteinPNet consistently identifies biologically meaningful prototypes aligned with different tumor subtypes. Through graphical and morphological analyses, we show that these prototypes capture interpretable features pointing to differences in immune infiltration and tissue modularity. Our results highlight the potential of prototype-based learning to reveal interpretable spatial biomarkers within the TME, with implications for mechanistic discovery in spatial omics.
format Preprint
id arxiv_https___arxiv_org_abs_2512_02983
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle ProteinPNet: Prototypical Part Networks for Concept Learning in Spatial Proteomics
McConnell, Louis
Sun, Jieran
Maffei, Theo
Gottardo, Raphael
Rapsomaniki, Marianna
Machine Learning
Understanding the spatial architecture of the tumor microenvironment (TME) is critical to advance precision oncology. We present ProteinPNet, a novel framework based on prototypical part networks that discovers TME motifs from spatial proteomics data. Unlike traditional post-hoc explanability models, ProteinPNet directly learns discriminative, interpretable, faithful spatial prototypes through supervised training. We validate our approach on synthetic datasets with ground truth motifs, and further test it on a real-world lung cancer spatial proteomics dataset. ProteinPNet consistently identifies biologically meaningful prototypes aligned with different tumor subtypes. Through graphical and morphological analyses, we show that these prototypes capture interpretable features pointing to differences in immune infiltration and tissue modularity. Our results highlight the potential of prototype-based learning to reveal interpretable spatial biomarkers within the TME, with implications for mechanistic discovery in spatial omics.
title ProteinPNet: Prototypical Part Networks for Concept Learning in Spatial Proteomics
topic Machine Learning
url https://arxiv.org/abs/2512.02983