clinical data scientists

Abstract: Deep learning models for dynamic survival analysis (DSA) achieve strong predictive performance by incorporating longitudinal patient data, but their black box nature limits clinical trust and adoption. Existing explainability methods cannot handle longitudinal, irregular inputs and functional survival outputs simultaneously, which limits their usability in DSA. We propose DynSHAP, a SHAP framework suited specifically for dynamic survival analysis. It extends common marginal SHAP estimators to this setting by treating time--feature pairs as players in the Shapley game. We further introduce Temporal DynSHAP, which learns linear dependencies in features over time and uses conditional sampling to address them in explanations. When applied to synthetic data with known ground-truth attributions, Temporal DynSHAP recovers temporally dependent features more accurately than marginal estimators for a given state-of-the-art model. Applied to two real-world clinical datasets and two DSA architectures, DynSHAP produces attributions faithful to model learning, allowing medical experts to see which patient information drove the prediction and when.

Abstract: Objective Prediction models are commonly trained using objectives such as Bernoulli negative log-likelihood (NLL), although downstream clinical decisions may depend on specific risk thresholds. We introduce Smooth Net Benefit ($σ$NB), a differentiable approximation of Net Benefit designed to align model training with threshold-specific clinical utility. Materials and Methods We evaluated $σ$NB as a training objective for logistic regression, generalized additive models (GAMs), and XGBoost with three Hessian implementations. Experiments used the Framingham cardiovascular risk dataset and 44 TabZilla datasets comprising 72 dataset-threshold combinations. Results $σ$NB training did not consistently improve Net Benefit in Framingham. Across the TabZilla benchmark, mean standardized Net Benefit for logistic regression increased from 0.5669 with NLL to 0.5765 with $σ$NB (mean difference 0.0096, 95% CI -0.0001 to 0.0193). For GAMs, mean standardized Net Benefit decreased from 0.5921 to 0.5625 (mean difference -0.0296, 95% CI -0.0721 to 0.0129). For XGBoost, NLL achieved 0.6745 compared with 0.6723--0.6735 across $σ$NB implementations. In logistic regression, $σ$NB gains were positively associated with the performance advantage of XGBoost over NLL-trained logistic regression. Discussion The effect of $σ$NB was context dependent, with modest gains concentrated in logistic regression and little benefit for more flexible model classes. This suggests that decision-focused optimization may be most useful when limited model flexibility leaves greater scope for improvement. Conclusion Our results do not support $σ$NB as a general replacement for NLL training, but support further investigation of decision-focused objectives in settings where conventional likelihood-based training may not adequately capture decision-relevant structure.

Abstract: Genetic Programming and its variants, such as grammatical evolution, are widely used in Symbolic Regression to derive mathematical expressions from multivariate data. In addition to predictive accuracy, models are appreciated for their potential to provide interpretability, offering explicit equations that relate input variables to outcomes. However, achieving interpretability and plausibility remains challenging, as evolved models may be complex or scientifically inconsistent. In this study, we explore whether Large Language Models, can assist in improving the explainability of Symbolic Regression models generated by evolutionary computation methods. Building upon our previous work on estimating body fat percentage using grammar-based Genetic Programming , we investigate the use of LLMs as post-processing tools to analyze and rank evolved expressions according to their interpretability and medical plausibility. Four symbolic expressions are analysed by three LLMs over three repeated runs, and the resulting interpretations and rankings are assessed by a panel of three clinicians. Across the three LLMs, comparative model-ranking outputs received more favorable clinician assessments than isolated term-level interpretations. However, the LLMs also produced physiologically and mathematically questionable explanations, indicating that they are better suited to comparative auditing under expert oversight than to autonomous validation.\blfootnote{The present work is an extended version of a paper submitted into a journal.

Abstract: Longitudinal single cell atlases now capture matched pre treatment and post treatment states from responders and non responders, presenting an opportunity to mechanistically explain why two patients on the same drug diverge. We introduce scDEFT (single cell Drug EFfect Transducer), which treats a drug as a conditioning operator on cell representations, enabling prediction and explanation. In scDEFT, feature wise linear modulation produces drug conditioned cell latents, learned under abundant per cell supervision and then frozen. Two independent heads aggregate those latents over shared transcriptional neighborhoods to predict drug induced state change and responder status. A backward stage ranks the latent dimensions by how strongly they separate responders from non responders and maps them to genes under a cell composition control. On a harmonized inflammatory bowel disease atlas of 1.16 million cells, three cohorts and two drug classes, scDEFT predicts state change at 45% of the baseline to reproducibility ceiling headroom and stratifies responders before treatment at AUROC 0.70, where standard predictors remain at chance. These predictions and the drivers behind them support target and co target nomination, patient stratification, and counterfactual prediction of unseen drug cohort effects.

Abstract: In this work, we introduce language-aligned motion representations for domain-generalizable UPDRS-Gait severity estimation, aiming to learn semantically structured motion features that generalize across heterogeneous clinical domains. We first learn motion representations using a Bi-GRU backbone that captures the temporal dynamics of SMPL sequences. Prior to model training, motion captions are generated offline using Qwen2.5-7B-Instruct. The backbone is then trained with both classification and text-alignment objectives to learn discriminative and semantically structured motion representations while accounting for the class imbalance present in the training data. We subsequently adapt the learned backbone independently to each source domain so that the model can capture domain-specific motion characteristics. The resulting source-specific models are then merged at the parameter level to consolidate complementary knowledge across source domains into a single domain-generalized model. To further mitigate class imbalance, we perform GPT-5.5-based pseudo labeling, and our final merged models for each site do not use any class-prior correction during inference. The resulting model is evaluated under the unseen-site setting of the MoCha Challenge, using Macro F1 as the primary evaluation metric. Our method achieves a macro-F1 of 0.57 on the hidden test set with only 637K active parameters at inference, ranking 3rd among 58 leaderboard entries in the MoCha 2026 Challenge. The challenge attracted 1,669 submissions from 112 participants and offered monetary prizes sponsored by Machine Medicine Technologies.

Abstract: Sample size determination for machine learning (ML) prediction models is challenging because conventional power analysis typically requires the predictor-outcome relationship and effect structure to be specified a priori. Nonlinear ML models learn complex prediction surfaces that do not admit straightforward analytical power calculations. We propose a framework that approximates nonlinear ML models with localized linear representations and estimates sample size requirements by evaluating statistical power across these local regions.

Abstract: Normative age models are trained to predict chronological age in a nominally healthy cohort. Applied to patients, they deviate, and the gap between predicted and chronological age is read as disease risk. Here, we attribute the disease-related effect size of the age gap directly to individual training samples, rather than using a prediction-level loss as the attribution target. For Cohen's $d$, the resulting closed-form influence functional, validated against leave-one-out retraining, ranks training samples by their effect on held-out case-control separation. Across four diseases and two biomarker modalities in UK Biobank, removing the 10% most influential training samples raises held-out disease-related effect size in every seed. It more than doubles the metabolomic-age effect for type-2 diabetes and raises the brain-age effect for multiple sclerosis by roughly a third. Random removal leaves effect size flat even at 50% removal, confirming the gain comes from which samples are removed, not how many. Flagged subjects carry subclinical cardiometabolic burden that diagnosis-based exclusion misses, on markers the model never sees. For type-2 diabetes, where the method gains most, the marker recovered is HbA1c, the standard measure of blood sugar control. We release pyinfluence, our influence-function package, for reproducibility and reuse.