Concept-based explanation of gene expression prediction from H&E images

Recent advances in pathology foundation models have enabled accurate prediction of spatial transcriptomics (ST) from routine H&E images. However, existing explainability methods for vision transformer (ViT)-based models are largely limited to local heatmaps and do not reveal how morphological concepts contribute to ST predictions. Here, we introduce an explainable framework that combines relevance propagation and concept discovery to link transcriptional programs to tissue morphology. We developed a ViT-based framework for virtual ST from H&E images that combines ViT-aware layer-wise relevance propagation with relaxed archetypal TopK sparse autoencoder-based concept discovery. This approach provides both local explanations and global insights into the morphological patterns associated with transcriptional programs. We applied the framework to colorectal cancer ST data from the HEST-1k cohort and evaluated its generalizability in TCGA COAD. Our architecture accurately predicts clinically relevant ST signatures and accompanying molecular phenotypes. Measured and predicted gene expression profiles reveal substantial spatial heterogeneity of the colorectal cancer subtypes iCMS2 and iCMS3 across a large number of samples. Spatially resolved and aggregated iCMS classification achieve weighted F1 scores of 0.872 and 0.819 (0.770 in TCGA COAD), respectively, and both stratify patient outcome. Beyond prediction, our framework establishes a relevance-based concept atlas linking molecular phenotypes to histopathological representations. Comparison of activation- with relevance-derived concepts demonstrates that relevances provide a more direct link between tissue morphology and downstream predictions. We establish a general strategy for concept-based explanation of spatial prediction, and our framework is readily applicable to a broad range of ViT-based pathology models.

Agent-Guided Relational Concept Discovery: Toward Interpretable Surgical Margin Assessment

Deep learning models can effectively use Rapid Evaporative Ionization Mass Spectrometry (REIMS) data for surgical margin assessment. However, their clinical adoption remains challenging due to limited generalization to operating room conditions. This difficulty arises because models are typically trained on labeled spectra collected from resected tissue samples, while they must operate on noisy, unlabeled data acquired directly during surgery. In addition, the black-box nature of deep learning models makes it difficult to understand and systematically improve their behavior. Concept-based learning offers a promising way to address these challenges by mapping raw measurements to human-understandable concepts. However, supervised concept-based approaches rely on concept annotations, which are difficult to obtain in complex mass spectrometry workflows. We propose Agent-Guided Concept Discovery, a framework that learns meaningful concepts directly from data without requiring predefined concept labels. During training, a reasoning agent refines semantic descriptions of the learned concepts and adaptively adjusts their weight based on diagnostic relevance. These concepts are further grounded using a biochemical knowledge graph to ensure consistency with known metabolic relationships. Across Skin and Breast Cancer datasets, our model improves balanced accuracy and sensitivity over the baseline. In a representative intraoperative case, it shows fewer false positives, indicating better generalization to surgical conditions.

Retrieval is Enough: Training-Free Interpretability with a Tool-Using Agent

Interpretability methods for neural network activations span a wide cost spectrum, from cheap, training-free techniques (such as linear probes, PCA, SVD) to more expensive training-based ones (such as SAEs and activation oracles). Training-based methods are typically more powerful, in part because they leverage large activation datasets during training. This raises a natural question - do they actually surface insights that go beyond what is recoverable from the training dataset itself? To address this, we equip an LLM agent with a vector database of activations paired with their textual contexts, along with tools for manipulating activations - projecting out directions in latent space, computing activation differences and averages. The agent iteratively queries the database, forms hypotheses from the retrieved samples, and validates them by constructing linear probes. We call this method HARP, for Hypothesis-driven Agentic Retrieval and Probing. Despite not involving any training, HARP outperforms both activation oracles and SAE-based agents on concept discovery, concept detection, model steering, and secret elicitation. The training-free design also makes HARP substantially cheaper and more flexible: new datasets can be indexed on demand whenever existing ones prove insufficient. More broadly, our results suggest that current training-based methods do not yet extract insights beyond their training data, and motivate benchmarks that explicitly require interpretability methods to demonstrate such insights. We release our code at https://github.com/SriramB-98/HARP

Driving the Wrong Way: Leveraging Interpretability in End2End Autonomous Driving Models

The increasing adoption of end-to-end learning for autonomous driving introduces increased model complexity and opacity, raising the risk of learning undesired or erroneous behavior. In this work, we integrate unsupervised dictionary learning as a post hoc interpretability module within state-of-the-art driving models to decompose driving behavior into semantically meaningful concepts while demonstrating their causal influence on the model's driving decisions. We propose a stepwise framework for extracting and interpreting meaningful concepts from the end-to-end model and connecting them to the multifaceted model outputs, thereby revealing the underlying decision-making logic for the prediction of future trajectories. Furthermore, targeted interventions at the concept level allow us to manipulate and correct driving decisions, resulting in measurable improvements in overall driving performance. We thus demonstrate how interpretability can effectively be used to reduce model opacity, uncover erroneous behavior, and enable targeted mitigation, ultimately boosting model performance.

S$^2$COPE: Self-Supervised Concept Discovery via Preference Learning

Current representation learning paradigms force a fundamental compromise: self-supervised methods scale to massive datasets but yield opaque features, whereas interpretable models remain bottlenecked by the need for dense human annotation. We introduce Self-Supervised Concept discOvery via Preference lEarning (\model), a label-free framework that resolves this dilemma. Instead of treating Vision-Large-Language Models (VLLMs) as static feature extractors, \model leverages them as active participants in a self-supervised preference optimization loop. By autonomously hypothesizing, validating, and reinforcing candidate visual attributes directly from raw imagery, our framework discovers novel, structured concepts without a single label. Extensive experiments across natural, medical, and physics domains demonstrate that \model successfully extracts domain-specific concepts where standard VLLMs often fail to generate. By amortizing concept discovery directly into the VLLM backbone through our self-supervised preference objective -- rather than relying on static generation and disjoint filtering -- we achieve up to a 24-point absolute improvement in downstream top-1 classification accuracy on unseen data. Our work suggest that interpretability can emerge through a model's autonomous interaction with incidental visual structures, without any human supervision.