Interpretable Multiple Myeloma Prognosis with Observational Medical Outcomes Partnership Data

We develop and analyze explainable machine learning (ML) models for sepsis outcome prediction using a novel Electronic Health Record (EHR) dataset from 12,286 hospitalizations at a large emergency hospital in Romania. The dataset includes demographics, International Classification of Diseases (ICD-10) diagnostics, and 600 types of laboratory tests. This study aims to identify clinically strong predictors while achieving state-of-the-art results across three classification tasks: (1)deceased vs. discharged, (2)deceased vs. recovered, and (3)recovered vs. ameliorated. We trained five ML models to capture complex distributions while preserving clinical interpretability. Experiments explored the trade-off between feature richness and patient coverage, using subsets of the 10--50 most frequent laboratory tests. Model performance was evaluated using accuracy and area under the curve (AUC), and explainability was assessed using SHapley Additive exPlanations (SHAP). The highest performance was obtained for the deceased vs. recovered case study (AUC=0.983, accuracy=0.93). SHAP analysis identified several strong predictors such as cardiovascular comorbidities, urea levels, aspartate aminotransferase, platelet count, and eosinophil percentage. Eosinopenia emerged as a top predictor, highlighting its value as an underutilized marker that is not included in current assessment standards, while the high performance suggests the applicability of these models in clinical settings.

We introduce Retrieval-Augmented Interpretable Learning (RAIL), a probabilistic meta-learning framework for zero-shot generation of task-specific interpretable models that synthesizes coefficient-space structure from natural-language task descriptions and a memory of previously learned task-specific predictors. RAIL retrieves related source tasks, transfers structure through coefficient space, and generates a new predictor in the original diagnostic-feature space, enabling zero-shot and few-shot clinical procedure prediction with feature-level explanations. Its probabilistic formulation provides uncertainty over retrieval, model coefficients, and predictions, supporting uncertainty-aware deployment: uncertain predictions or unstable explanations can be flagged for additional clinical review rather than treated as automatic decisions. This makes RAIL particularly suited for healthcare settings, where prediction tasks are highly long-tailed, new clinical targets arise frequently, and models must remain inspectable, uncertainty-aware, and compatible with human oversight. Across long-tailed clinical procedure prediction tasks, RAIL improves low-data model generation, benefits from clinically informed task representations, and yields retrieval, uncertainty, and coefficient-level diagnostics that make model behavior more transparent. These results suggest a path toward scalable clinical prediction systems that can adapt to new tasks while preserving interpretability and reliability.

Alzheimer disease (AD) diagnosis and prognosis increasingly rely on machine learning (ML) models. Although these models provide good results, clinical adoption is limited by the need for technical expertise and the lack of trustworthy and consistent model explanations. SHAP (SHapley Additive exPlanations) is com-monly used to interpret AD models, but existing studies tend to focus on explanations for isolated tasks, providing little evidence about their robustness across disease stages, model architectures, or prediction objectives. This paper proposes a multi-level explainability framework that measures the coherence, stabil-ity and consistency of explanations by integrating: (1) within-model coherence metrics between feature importance and SHAP, (2) SHAP stability across AD boundaries, and (3) SHAP cross-task consistency be-tween diagnosis and prognosis. Using AutoML to optimize classifiers on the NACC dataset, we trained four diagnostic and four prognostic models covering the standard AD progression stages. Stability was then evaluated using correlation metrics, top-k feature overlap, SHAP sign consistency, and domain-level contribution ratios. Results show that cognitive and functional markers dominate SHAP explanations in both diagnosis and prognosis. SHAP-SHAP consistency between diagnostic and prognostic models was high across all classifiers, with 100% sign stability and minimal shifts in explanatory magnitude. Domain-level contributions also remained stable, with only minimal increases in genetic features for prognosis. These results demonstrate that SHAP explanations can be quantitatively vali-dated for robustness and transferability, providing clinicians with more reliable interpretations of ML pre-dictions.