Nooshin Maghsoodi, Amoon Jamzad, Robert Policelli +11cs.AI
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.
De novo peptide sequencing from tandem mass spectrometry is pivotal in proteomics, enabling identification of novel peptides without reference databases. While recent Transformer-based encoder-decoder models have achieved remarkable performance, we uncover a critical pathology in their inference dynamics. Through comprehensive feature scaling experiments, we demonstrate that existing auto-regressive peptide decoders tend to over-rely on generated-sequence priors while progressively under-utilizing fine-grained physical evidence from the input mass spectrum. This phenomenon leads to suboptimal results, where generated peptide sequences are biologically plausible yet not faithful to the input spectrum. To rectify this, we propose MemNovo, a training-free and plug-and-play mechanism that re-balances peptide and spectral contributions at inference time. MemNovo alleviates the information bottleneck by establishing a persistent spectral memory bank and injecting retrieved features directly into the final decoding stage via an ultra-conservative residual connection. Theoretical analysis confirms that this mechanism restores the mutual information between the decoder state and the raw spectrum. Extensive experiments on the Nine Species benchmark with two representative baselines, Casanovo and InstaNovo, demonstrate that MemNovo consistently improves both amino acid precision and peptide precision, achieving up to 39.1% relative improvement in peptide precision for Casanovo and up to 3.9% for InstaNovo, with negligible computational overhead.