# ProteinPNet: Prototypical Part Networks for Concept Learning in Spatial Proteomics

arXiv: https://arxiv.org/abs/2512.02983 · HTML: https://mlsanity.com/paper/2512.02983/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 16 of its 40 references that are in the map.
- First posted on arXiv 2 Dec 2025.

## Builds on (most cited first, 16 of 16)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Grad-CAM: Visual Explanations from Deep Networks via Gradient-based Localization](https://mlsanity.com/paper/1610.02391/) (2016)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [This Looks Like That: Deep Learning for Interpretable Image Recognition](https://mlsanity.com/paper/1806.10574/) (2018)
- [GNNExplainer: Generating Explanations for Graph Neural Networks](https://mlsanity.com/paper/1903.03894/) (2019)
- [Interpretable Machine Learning: Fundamental Principles and 10 Grand Challenges](https://mlsanity.com/paper/2103.11251/) (2021)
- [Attention Mechanisms in Computer Vision: A Survey](https://mlsanity.com/paper/2111.07624/) (2021)
- [The Dangers of Post-hoc Interpretability: Unjustified Counterfactual Explanations](https://mlsanity.com/paper/1907.09294/) (2019)
- [XProtoNet: Diagnosis in Chest Radiography with Global and Local Explanations](https://mlsanity.com/paper/2103.10663/) (2021)
- [IAIA-BL: A Case-based Interpretable Deep Learning Model for Classification of Mass Lesions in Digital Mammography](https://mlsanity.com/paper/2103.12308/) (2021)
- [Layerwise Relevance Visualization in Convolutional Text Graph Classifiers](https://mlsanity.com/paper/1909.10911/) (2019)
- [MProtoNet: A Case-Based Interpretable Model for Brain Tumor Classification with 3D Multi-parametric Magnetic Resonance Imaging](https://mlsanity.com/paper/2304.06258/) (2023)
- [This Looks Better than That: Better Interpretable Models with ProtoPNeXt](https://mlsanity.com/paper/2406.14675/) (2024)

## Abstract (arXiv)

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.