Interpreting Protein Language Model Embeddings via Orthogonal Projection for Protein Fitness Prediction

Recently, there has been a growing adoption of protein language models (PLMs) in biomedical science. Their embeddings provide a rich numerical representation of protein sequences which achieve state-of-the-art performance on several downstream tasks including protein fitness prediction. However, PLM embeddings are not directly interpretable and, thereby, it remains unclear what features they encode. To gain insight into which biochemical properties of the protein are driving the prediction, we leverage an orthogonal projection technique that removes linear effects of known tabular features from embeddings and extend it to high-order and interaction effects. In this way, we remove the effects of interpretable biochemical features from PLM embeddings. In an ablation study, we show that this leads to a decrease in performance for a downstream classifier trained only on the embeddings to predict protein fitness. In an additional evaluation, we find that these biochemical features explain a substantial part of the variance in the predictions of this classifier. Hence, we can show that PLM embeddings encode patterns correlated with biochemical properties and quantify their contribution to predicting protein fitness. This computationally efficient approach is not limited to the features or embeddings considered here and is readily transferable to problem settings beyond protein fitness prediction.

Contrastive Learning for Interpretable Anomaly Detection at Collider Experiments

Generic event-level anomaly detection for collider physics has two recurring problems: anomaly scores are hard to interpret, and they correlate strongly with energy scale and object multiplicity. We present Organized Representation via Contrastive learning for Anomaly detection (ORCA), a two-stage framework that first learns an embedding space via supervised contrastive learning across a diverse set of physics processes, then runs a standard autoencoder in that space to generate event-level anomaly scores. On a simulated dataset consistent with conditions at the High-Luminosity Large Hadron Collider, ORCA delivers significant gains in both breadth and depth of sensitivity to new physics signals with respect to a baseline autoencoder architecture. Beyond improved sensitivity, the contrastive embedding makes the anomalous sample interpretable: because known processes occupy distinct regions of the space, a maximum-likelihood template fit to the embedding distributions can attribute events in an anomalous sample to template physics processes with quantified uncertainties. We demonstrate that the fit accurately recovers injected signal yields, including for signals excluded from the training of the embedding, and characterizes signals absent from the template library through the known processes they most resemble. These results establish ORCA as a route to interpretable anomaly detection-based searches at colliders, where the embedding geometry carries higher dimensional physics information compared to standard one-dimensional output fits, enhancing downstream statistical analysis.