ProteinPNet: Prototypical Part Networks for Concept Learning in Spatial Proteomics

Louis McConnell, Jieran Sun, Theo Maffei, Raphael Gottardo, Marianna Rapsomaniki

Submission Track: Short papers presenting ongoing research or work submitted to other venues (up to 5 pages, excluding references)

Keywords: interpretability, omics, spatial, prototype

TL;DR: tl;dr: we applied prototype part networks to spatial proteomics data to discover spatial motifs.

Abstract: 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. Code available at https://drive.google.com/file/d/1_9VCzTVpxE9QdE0eSxgC3jkb_zpsb3M4/view

Submission Number: 18