Clinical Outcome Prediction

Momentum

18 papers in the last four weeks, up 157% on the four weeks before. 0.2% of all new papers.

Jul 13Week of Sep 28

Latest papers 174

Oct 6, 2026cs.LG

GeneICL: A Tabular Foundation Model for Bulk Transcriptomics

Gene expression is widely measured in biomedicine, yet clinical outcome prediction remains challenging due to high dimensionality, strong feature correlations, and limited labeled data. Large self-supervised transcriptomic foundation models often fail to outperform simple supervised baselines. Tabular foundation models offer an alternative through in-context learning, but are typically pretrained on generic synthetic data rather than transcriptomic structure. We ask whether transcriptomics-aware pretraining, rather than scale, is the missing ingredient. Towards this end, we introduce GeneICL, a 4.2M-parameter tabular foundation model combining a semi-synthetic pretraining prior built from measured bulk expression profiles with a parameter-efficient recurrent architecture. We further enable right-censored survival prediction via a training-free reduction to regression using Cox partial-likelihood residuals. We evaluate GeneICL on 80 clinical outcome-prediction tasks spanning classification, regression, and survival. Tabular foundation models consistently outperform self-supervised transcriptomic models, while GeneICL achieves the best overall rank among evaluated foundation models and tuned baselines. GeneICL does so with up to 387×\times fewer parameters, no gradient updates at inference, and predictions within seconds on a laptop CPU.
Oct 6, 2026cs.CL

No Transformer Beats Six Covariates: Long-Horizon Prediction of Depressive Symptoms from Childhood Essays

Natural language processing (NLP) models can detect depression-related language in text written near the time symptoms are measured, but whether pretrained transformers can predict depressive symptoms from text written twelve years earlier is largely untested. In the National Child Development Study, a British birth cohort, we predict probable depressive symptoms at age 23 from essays the same people wrote at age 11. Our baseline, a logistic regression on six childhood covariates, outperforms every text model that sees only the essay: seven fine-tuned transformers, a bag-of-words model, frozen embeddings and four zero-shot large language models. Its area under the receiver operating characteristic curve (AUC-ROC) is 0.737 against 0.670 for the best transformer on the primary seed, and no added text score detectably raises the baseline's AUC-ROC. None of the five domain-pretrained transformers detectably beats its general-domain control after Bonferroni correction. For long-horizon prediction, the baseline remains the model to beat.
Oct 1, 2026cs.LG

GLoC-EHR: Evidence-Cited Clinical Reasoning over Global Context and Local EHR Events

Structured electronic health records (EHRs) contain a patient's clinical trajectory as a sequence of clinical codes. Answering clinical questions from such records requires both the context of the whole trajectory and the specific events that support the answer. We introduce GLoC-EHR, a multimodal language model that reads a contextual encoding of the record through a fixed-size global memory of the trajectory and a local memory of selected events. The model learns to generate hospital-course summaries from the global memory and descriptions of masked concepts from the local memory, aligning both with clinical text. It is then trained to cite evidence before answering, through rationale fine-tuning followed by group relative policy optimization (GRPO) with rewards for correct answers and record-supported evidence. On three MIMIC-IV outcome tasks, GLoC-EHR attains the highest macro AUROC among the compared models when it answers directly, whereas zero-shot LLMs reading the serialized record fall far behind. With evidence-cited reasoning, it stays close to its direct multi-task counterpart in macro AUROC, and the evidence terms of the objective reduce unsupported evidence at a similar macro AUROC. The local memory adds distinct supported findings, particularly under strict matching, without a detectable change in macro AUROC. Without retraining, GLoC-EHR transfers to EHRSHOT on par with EHR-BERT and answers two unseen laboratory questions better than zero-shot prompting of its own backbone.
Oct 1, 2026cs.LG

Fixing a Model That Learned Worse Cancer Means Lower Risk: Monotonic Constraints in Bladder Cancer Recurrence Prediction

Background and Objective: Clinicians expect recurrence risk to climb with cancer severity. In a UK multicentre trial, an unconstrained XGBoost model learnt that higher tumour stage and carcinoma in situ predicted lower recurrence risk, and discrimination, calibration, and SHAP were all blind to it. We developed a counterfactual testing framework to detect this inversion and a monotonic-constraint framework to remove it without hurting performance. Methods: BOXIT enrolled 472 patients with protocol-mandated cystoscopy across 51 UK sites (2007-2012); 435 had at least two years' follow-up (153 recurrences, 35.2%). We developed a counterfactual direction test and a monotonic-constraint correction, with constraint directions drawn from the EORTC and EAU risk systems, and evaluated both against unconstrained XGBoost and logistic regression on 18 predictors (seven directed) over 50 cross-validation folds. The test worsened each patient on one directed feature at a time to check whether risk fell; SHAP direction and calibration were also assessed. Key Findings and Limitations: Tumour stage and carcinoma in situ were associated with lower recurrence, opposite to medical intuition; the unconstrained model reversed carcinoma in situ counterfactuals in 90.2% of cases and stage in 74.3%. Discrimination (ΔΔAUC 0.005, p=0.47), calibration, and SHAP magnitude were all blind to the inversion. Monotonic constraints eliminated every violation at no cost to discrimination (0.723 vs 0.718) and outperformed EORTC (p=8.9e-16). Limitations: single trial, internal-external validation only. Conclusions and Clinical Implications: A model that had learned this inversion passed every conventional check. A counterfactual direction test, run as a single refit with pre-specified monotonic constraints, catches this failure at no cost to performance and should be routine before clinical deployment.
Sep 30, 2026cs.LG

Fusion techniques of time frequency-based images to predict the outcome of rTMS depression therapy

Depression is a mental condition that can lead to suicide and self-harm. Predicting the outcome of depression treatment is one of the most difficult tasks for clinicians. Among various treatment options, repetitive Transcranial Magnetic Stimulation (rTMS) is a widely used non-invasive method. Predicting rTMS response using Electroencephalogram (EEG) data is difficult because of high inter-subject variability and limited features from single-domain analysis. We introduce two fusion techniques, montage and blending, to overcome these limitations and extract richer features from EEG-derived Time-Frequency (TF) images. We then propose a lightweight custom Convolutional Neural Network (CNN) trained on fused TF representations. \textcolor{black}{We use a primary dataset of 15 patients and a secondary dataset of 46 patients. We run two sets of experiments. The first set uses segment-level 10-fold cross-validation. In this setup segments from the same patient can appear in both training and testing. The Montage CWT_ST fusion reaches 99.90% accuracy on the primary dataset and 91.90% on the secondary dataset. The second set uses strict subject-disjoint cross-validation. All segments of a patient stay in one fold and no patient appears in both training and testing. Performance collapses. We test four time-frequency methods, six fusion mechanisms, and fourteen model architectures. With one exception, every configuration on both cohorts falls between AUC 0.31 and 0.54 and every 95% confidence interval contains 0.5. A patient-level permutation test on the best standalone method returns p=0.703p = 0.703. The best subject-level result is Montage CWT_ST on the primary cohort, which reaches AUC 0.874±0.1830.874 \pm 0.183 and 82.7% accuracy.
Sep 30, 2026cs.CV

From Image Interpretation to Clinical Reasoning: Upstream Physician-Context-Aware Multimodal Learning with Causal Reinforcement Learning

Major adverse cardiovascular events (MACE) remain the leading cause of mortality worldwide. Opportunistic screening using routinely acquired clinical data offers a scalable approach for identifying high-risk individuals before acute events occur. Although chest X-rays (CXRs) capture latent cardiovascular biomarkers and clinical histories provide complementary patient context, existing medical vision-language models are primarily optimized for radiology interpretation rather than prognostic reasoning. We propose a causal reinforcement learning framework for multimodal clinical reasoning that integrates CXRs and physician-authored clinical histories for opportunistic MACE prediction. The framework introduces (1) a role-decoupled dual-LLM architecture that separates reasoning from risk prediction, (2) a dual-action causal reinforcement learning policy for evidence selection and reasoning optimization, and (3) causal token pruning to learn compact multimodal representations. Evaluated on an internal cohort, an emergency department cohort, and the external MIMIC dataset, the proposed framework consistently outperformed unimodal baselines and state-of-the-art medical vision-language models, achieving AUROCs of 0.720, 0.760, and 0.845, respectively. It also substantially improved reasoning quality, achieving higher GREEN scores and higher expert preference while maintaining robust predictive performance across diverse patient populations.
Sep 24, 2026cs.CV

Deep learning of longitudinal visual fields predicts glaucoma progression rate and identifies fast progressors

Glaucoma is the leading cause of irreversible blindness, and timely identification of fast progressors is essential to prevent disability. Current practice estimates progression by ordinary least-squares regression of mean deviation (MD) on time, requiring 6--10 visual field (VF) tests over several years to obtain a reliable slope. We present GLAM (Glaucoma Longitudinal Analysis Model), a deep learning framework that ingests longitudinal Humphrey 24-2 total deviation sequences with five clinical features and predicts MD and visual field index progression rates using attention-based fusion and aleatoric uncertainty. On the open-access University of Washington Humphrey Visual Field dataset (4,276 patient-eyes), GLAM achieved an MD-rate mean absolute error of 0.139 dB yr−1^{-1} (R2=0.927R^2 = 0.927; 73.5% reduction over a ridge baseline) and an AUC of 0.990 for fast-progressor detection. VF-only deep learning can match multimodal pipelines for progression prognostication using routinely collected perimetry alone.
Sep 23, 2026cs.CV

Predicting the Progression of Adolescent Idiopathic Scoliosis

Adolescent Idiopathic Scoliosis is defined as a lateral curvature of the spine that develops during adolescence, without known cause. The condition can result in significant pain and disability, and often progresses rapidly during adolescence. The objective of this paper is to predict the progression of the condition in a temporal sequence from ages 9 to 24, as measured from a sequence of Dual X-ray Absorptiometry (DXA) scans. To this end, we train a transformer model that takes in the curve of the spine to predict curve progression. The model is trained using a large-scale synthetic dataset of spine curves and their time series, covering different curve types and different progression patterns. We show that the model is able to generalise from synthetic to real data by evaluating it on a dataset of real DXA scans covering multiple time points. We find that fine-tuning the model on real data gives a significant boost to performance. The model is able to accurately predict spine curve progression in both scoliosis and normal cases.
Sep 23, 2026cs.CL

Cross-Scale Transfer Learning for Depression Severity Prediction: From PHQ-8 to HAMD-17 Across Languages and Clinical Paradigms

This work addresses continuous depression-severity score prediction from clinical interview transcripts under data scarcity. We propose a sequential low-rank adaptation (LoRA) protocol for cross-scale transfer: a Qwen3 backbone with a bounded regression head is first fine-tuned on the English DAIC-WOZ dataset (189 avatar-mediated sessions, PHQ-8), and the adapter then initializes fine-tuning on the Chinese PDCH dataset (100 real clinical consultations, HAMD-17), where a reinitialised, scale-specific head predicts the clinician-assigned score. All configurations use patient-level stratified 5-fold, 2-repeat cross-validation. On the data-scarce HAMD-17 target, the sequential protocol attains the best point-estimate MAE , RMSE, and macro-F1F_1 on both 0.6B and 1.7B backbones, outperforming target-only training and non-LLM baselines---4.96/6.59/0.36 with Qwen3-0.6B and 4.38/5.62/0.46 with Qwen3-1.7B. Ablations suggest that correctly aligned source supervision gives the best point estimates (unsupervised exposure and shuffled-label controls also show partial gains), that native-Chinese target input outperforms machine-translated English input, and that the reversed order yields no clear gain within run-to-run variance. The study is an exploratory, single-site internal evaluation: it does not establish screening or diagnostic utility, nor separately identify the contribution of the scale, language, or paradigm shifts. To our knowledge, no prior study evaluates this specific DAIC-WOZ-to-PDCH sequential transfer setting.
Sep 20, 2026cs.LG

GLR-MM: Graph-Based Global-Local Reconstruction for Robust Multimodal Chest X-ray and EHR Representation Learning under Missing Modalities

Clinical multimodal models must often predict before all chest X-ray (CXR) and electronic health record (EHR) inputs are available. Existing approaches align observed representations, model missingness, or reconstruct across modalities, but do not jointly exploit within-patient and clinically similar inter-patient evidence. We propose GLR-MM, a Graph-Based Global-Local Reconstruction framework for early ICU mortality prediction. It maps five CXR-EHR modalities to a shared space, reconstructs missing embeddings through complementary local cross-modal and global graph-attention branches, adaptively fuses their estimates, and optimizes class-balanced prediction, reconstruction, and contrastive objectives. On 9,620 MIMIC-derived ICU stays, we evaluate 10%, 30%, and 50% random modality missingness with shared deterministic masks. MUSE performs better under mild and moderate missingness, whereas GLR-MM achieves higher AUROC and AUPRC at 50% by 0.0088 and 0.0249, respectively. These results indicate that graph-guided reconstruction is most useful when inputs are severely incomplete.
Sep 16, 2026eess.IV

Mammography Foundation Models for Opportunistic Prediction of Major Adverse Cardiovascular Events

Cardiovascular disease (CVD) remains the leading cause of death among women, yet cardiovascular risk assessment often relies on clinical variables that may be missing, outdated, or unavailable in routine care. Screening mammography offers an opportunity for opportunistic cardiovascular risk stratification because it is routinely acquired and contains vascular features, including breast arterial calcifications (BAC), that are associated with cardiovascular risk and events. We evaluate whether mammography specific foundation models, originally pretrained for breast cancer-related tasks, can transfer to cardiovascular risk prediction without cardiovascular specific supervision or explicit BAC annotation. We constructed a 5-year major adverse cardiovascular event (MACE) cohort of 22,497 women linked to electronic health record outcomes, including 500 events (2.22% prevalence). The foundation models achieved AUROCs of 0.823 and 0.822 substantially exceeding an age-only model (AUROC 0.765), despite using only the screening mammogram as input, with no clinical variables. Both foundation models evaluated assigned substantially higher predicted risk to patients with radiologist-documented BAC, despite BAC never being used as a training label, and showed activation patterns consistent with vascular findings. Together, these findings suggest that mammography foundation models can recover clinically relevant cardiovascular risk information directly from mammographic pixels and suggest that screening mammography may provide an opportunistic source of cardiovascular risk information to complement conventional clinical assessment without additional imaging. Code is available in https://github.com/PauFeld/MammoCVD
Sep 16, 2026cs.LG

Machine-Learning Assessment of the Predictive Value of Inflammatory Biomarkers for Cognitive Impairment in an Older Hispanic Adult Cohort

Small clinical tabular datasets require interpretable machine learning because deep learning is often impractical and ensemble models can be difficult to inspect. A key pitfall is that statistical significance does not necessarily imply predictive utility. Using data from the Panama Aging Research Initiative--Health Disparities (PARI-HD) cohort (n=165), we implemented a leakage-safe threshold-likelihood Bernoulli/Categorical Naive Bayes (BNB/CNB) classifier. Within every training fold, each continuous predictor was reduced to a supervised chi-square-derived state, while income entered the model through a categorical likelihood. All data-dependent steps were performed within repeated stratified 10-fold cross-validation with 30 repeats. The demographic baseline achieved a ROC-AUC of 0.630 +/- 0.017. I-309 (CCL1) was the dominant incremental feature, increasing AUC by 0.110, with paired DeLong tests yielding p<0.05 in 100% of repeats. In the pre-specified primary analysis, I-309 produced a fixed-partition DeLong p=0.0018, with robustness assessed across 200 random partitions, where the median p-value was 0.0011. Within the exploratory family of 18 candidate markers, I-309 achieved a Benjamini-Hochberg-adjusted q=0.032 on the frozen partition and satisfied q<0.05 in 85% of random partitions, whereas no other marker demonstrated reliable incremental predictive value. Because the fitted model is an inspectable table of thresholds and class-conditional probabilities, these results identify I-309/CCL1 as an interpretable candidate feature for tabular prediction of cognitive impairment, pending external validation.
Sep 16, 2026cs.CL

EviGen: Predictive Evidence Scaffolding for Verifiable Clinical Rationale Generation

Longitudinal electronic health records (EHRs) capture years of patient history across notes, codes, labs, and procedures, and contain evidence needed to reason about likely clinical outcomes. However, comprehensive clinician review of these records is impractical, and LLM-based processing is costly and often unreliable, missing some relevant observations while hallucinating others. We therefore propose EviGen, a three-layer framework for verifiable clinical rationale generation that addresses these challenges. The first layer is a patient-conditioned retriever that uses learnable queries to find evidence predictive of, not just textually relevant to, a clinical outcome and ranks it by prediction attribution scores. The second layer is an LLM generator that consumes this ranked evidence as a scaffold to produce a clinical rationale grounded in the retrieved spans. The third layer is a process-supervised verifier that checks the generated rationale at the reasoning-step level, flagging unreliable claims. Across three medical prediction datasets, EviGen improves prediction performance and rationale faithfulness over full-context LLM and RAG baselines, and is preferred by clinical reviewers in a usability evaluation.
Sep 14, 2026cs.AI

LongAgent: History-Guided Agentic Search for Longitudinal Outcome Prediction

Extracting informative representations from longitudinal data that can predict future outcomes remains a critical challenge in medicine. Medical datasets are inherently heterogeneous, consisting of a large number of variables collected from different sources, sampled with different temporal spacings, and representing different aspects of human health status. This requires identifying those variables with predictive value, processing longitudinal information, and integrating multiple variables for outcome prediction. Here, we propose a novel agent-based approach, LongAgent, that can autonomously search over combinations of variable sets, temporal windows and longitudinal aggregation functions, and identify candidates with promising predictive performance. LongAgent utilises a history memory of previous searches and numerical evidence to guide subsequent exploration. On synthetic data, LongAgent achieves a mean prediction RMSE of 1.7376 and improves over the strongest non-agent baseline by 0.0151 (95% CI: [0.0045,0.0260]; p=0.0273). On a real clinical dataset, it performs comparably to the best baseline.
Sep 14, 2026cs.LG

Knowledge-Enriched Structured EHR Features for 30-Day Hospital Readmission Prediction on MIMIC-IV

Recent approaches to 30-day hospital readmission prediction rely on pre-trained language models applied to discharge summaries. Although these methods achieve strong performance, they depend on the availability of clinical notes, incur substantial computational costs, and yield representations that lack interpretability. We propose a knowledge-enriched feature representation that augments structured Electronic Health Record (EHR) data with four medical knowledge sources: disease ontology mapping, procedure classification, drug ingredient vocabulary, and organ system laboratory aggregation, without using clinical notes. Each feature dimension corresponds to a named clinical concept, yielding a sparse and interpretable patient representation. The approach is evaluated with six classifiers on a MIMIC-IV v2.2 cohort. Under 20-fold cross-validation, the best configuration achieves an AUROC of 0.743. This performance is comparable to that of previously reported methods on this dataset, including both those using only structured data and those incorporating clinical notes, while requiring considerably less computational cost. Interpretability analysis shows that demographics, organ system labs, drug ingredient features, and first-level ontology disease categories drive prediction, while deeper hierarchy levels contribute negligibly. These findings indicate that knowledge-enriched structured features offer a competitive and efficient alternative to embeddings from clinical notes for 30-day readmission prediction.
Sep 14, 2026cs.LG

Patient-Reported Survey Data Improve Prediction of Opioid Use Disorder

Electronic health records (EHRs) may incompletely capture patient-reported factors associated with opioid use disorder (OUD). We evaluated whether survey data improve prediction of a first recorded OUD diagnosis among 267,747 All of Us participants with documented opioid exposure, including 15,287 OUD cases. We compared EHR-only and EHR+survey models across 6-, 12-, and 24-month look-back windows using logistic regression, random forest, XGBoost, LightGBM, multilayer perceptron, LSTM, GRU, and Transformer. Survey augmentation improved PR-AUC across all 24 model-window combinations by 0.0087-0.0505; the best 24-month LightGBM model improved from 0.6219 to 0.6603. Survey coverage increased with longer windows and differed by OUD status (24 months: 21.7% OUD-positive vs. 60.7% OUD-negative). Permutation analysis ranked survey features as the second most important information domain at 24 months in both evaluated models. Patient-reported data provide complementary predictive signals beyond structured EHRs while highlighting the importance of survey availability.
Sep 14, 2026cs.LG

Reinforcement Learning over Patient Trajectories for Clinical Reasoning in EHR Foundation Models

Electronic health record (EHR) foundation models trained on longitudinal patient trajectories have demonstrated strong performance across diverse clinical prediction tasks. However, their clinical reasoning capabilities remain constrained by next-token prediction on limited and incomplete EHR data. To address this, we propose a reinforcement learning (RL) fine-tuning framework that treats EHR foundation models as generative policies over patient trajectories. We formulate common clinical prediction problems (e.g., hospital readmission) as event-conditioned, time-windowed reasoning tasks. We then design time-aware, rollout-sensitive rewards to account for finite rollout lengths and temporally inconclusive outcomes. We find that RL fine-tuning consistently improves over pre-trained backbones and strong baselines. Notably, it enables smaller models to surpass larger pre-trained models in data-limited regimes and induces positive transfer across tasks. Further analysis shows that RL fine-tuned models generate trajectories with stronger structural and semantic alignment to ground truth and greater downstream utility.
Sep 14, 2026cs.CV

Self-supervised Pre-training Helps Retinal Disease Progression Modelling Most When Data Is Scarce

Modelling how a disease progresses over time requires longitudinal imaging cohorts, which are scarce and small, whereas cross-sectional data -- one image per participant -- is abundant. Self-supervised pre-training on such data offers a way to bridge this gap, but it is unclear which strategy best supports progression modelling, or how that answer depends on the amount of labelled longitudinal data. We study this for age-related macular degeneration (AMD), pre-training encoders on the large cross-sectional NAKO cohort and predicting time to late AMD on the longitudinal AREDS dataset. We compare in-house self-supervised encoders against a general-purpose (DINOv2) and a domain-specific (RETFound) foundation model, across contrastive, masked-autoencoding, and self-distillation objectives, under frozen and fine-tuned protocols, and across labelled training sets from 100 to 32,250 examples. Which model performs best depends on how the encoder is used. When the encoder is frozen and labels are few -- the regime typical of longitudinal cohorts -- pre-trained representations reach clinically reasonable discrimination from a few hundred labelled samples, while models trained from scratch do not; this advantage fades under fine-tuning. Transfer is governed by the self-supervision objective rather than corpus scale or domain match, so that an encoder pre-trained on a modest cross-sectional cohort matches or exceeds a far larger in-domain foundation model. Together, these results offer a practical recipe for building progression models where longitudinal data is scarce: a frozen self-supervised encoder with a lightweight survival head.
Sep 9, 2026q-bio.QM

scDEFT: A deep learning framework for drug-effect prediction and counterfactual reasoning

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.
Sep 9, 2026cs.LG

In Medical Claims Data, Enhancing Predictive Performance for Major Adverse Cardiovascular Events Using Cross Attention

Medical claims data comprise the financial details, including the expenses and billing information, as well as the clinical information, such as the diagnoses and treatments, of patients visiting medical facilities. Recently, it has been acknowledged that large databases can be constructed from medical claims data for medical research purposes. However, the clinical information within these datasets is often medically unstructured, limiting its application in comprehensive analyses. This study enhances predictive model performance for major adverse cardiovascular events (MACE), a leading cause of death worldwide. Models that predict MACE are crucial to clinical practice guidelines. We utilize a cross-attention mechanism to develop a method that effectively weights the relationships between diagnoses and treatments. Effectively repre- senting the clinical information contained in medical claims data, this approach generates more representative features for predicting MACE. The ROC-AUC score of our proposed cross-attention-based model was 0.7720, higher than other benchmark models including the conventional atherosclerotic cardiovascular disease model, the light gradient boosting machine, and a self-attention-based model. These results indicate that integrating the clinical structure of medical claims data using a cross-attention mechanism significantly enhances the performance of predictive models.
Sep 5, 2026cs.LG

PhenoBench: Mapping What a Deeply Phenotyped Human Cohort Can Tell Us

Deeply phenotyped cohorts combine clinical, imaging, molecular, and wearable observations across timescales from seconds to years, but heterogeneous analyses are not directly comparable. We present PhenoBench, an executable benchmark that turns deep-phenotyping measurements into explicit questions and controlled comparisons of information sources and predictive models. It is built around the Human Phenotype Project, with more than 13,000 participants at the initial visit. Each question fixes the target, population, timing, and allowed information; its evaluation contract specifies the split, metric, baseline, and claim boundary. PhenoBench defines 90 clinically grounded tasks across 15 domains and 26 input modalities. Across 160 matched regression comparisons spanning 52 tasks, six pretrained tabular models ranked above the evaluated task-specific baselines, including XGBoost and CatBoost, under a fixed single-estimator protocol with bounded tuning. Giving each task equal weight, their mean advantage over ridge was 0.0103 R2R^2 (95% task-bootstrap interval, 0.0071-0.0136). We also evaluated 14 language models, collectively covering 40 tasks spanning phenotype recovery, classification, follow-up forecasting, and participant ordering. Without cohort-specific fitting, language models made informative predictions on some tasks but showed task-specific capability gaps, shared failures of scale, and rarely surpassed task-specific ridge or logistic regression models fitted on the same input fields. PhenoBench provides a versioned, auditable evaluation system where new questions, measurements, and models can be added without redefining existing comparisons.
Aug 31, 2026cs.LG

SMOTE-VAR: An Uncertainty-Aware Oversampling Method for Predicting Depression Remission in University Students

University students experience disproportionately high rates of common mental health conditions, such as depression, which can impair learning, social functioning, and overall well-being. Although lifestyle interventions such as mindfulness and physical activity can reduce the symptoms, many do not achieve symptomatic remission. Developing new approaches to identify students with poor outcomes could enable earlier and more targeted intervention. Machine learning (ML) methods have increasingly been used to predict remission in depressive patients. However, these ML models often suffer from class imbalance, where there may be an unequal proportion of people in the remitted group relative to the non-remitted group. This imbalance can reduce model accuracy and bias predictions. To address this, studies commonly employ the popular oversampling strategy SMOTE. However, SMOTE has a notable limitation: it may generate invalid synthetic minority samples. In a clinical context, these false positives can lead to incorrect risk stratification, potentially delaying necessary escalated care for patients unlikely to remit. In this paper, we introduce a novel and effective oversampling method that addresses this shortcoming. Our approach leverages the variance function of a Gaussian process to estimate the uncertainty of generated minority samples to reduce false positives. We validate our method on a depression dataset collected from university students and demonstrate that it is better than existing oversampling approaches in predicting remission (i.e., treatment outcome). By improving the reliable identification of non-responders, our method provides a robust computational tool to help clinicians rapidly pivot to adjunctive therapies, thereby personalizing and optimizing mental health care pathways.
Aug 30, 2026cs.LG

INTERVenE: Temporal-Abstraction-Interval Based Transformers for Short-Horizon Medical Event Prediction

Electronic Health Record (EHR) prediction models in the intensive care unit must learn from sparse and irregular measurements while preserving the clinical meaning of time and supporting transparent decision-making. We present INTERVenE, a family of Transformer architectures whose input is an interval-based, knowledge-based temporal abstraction (KBTA), a token stream of named clinical concepts (states, trends, events, contexts) drawn from a curated medical ontology, rather than an unnamed bin index or a raw measurement triplet. This naming layer is what we ask KBTA to do: it makes the model's per-token attributions resolve to clinical concepts by construction. INTERVenE offers two complementary variants: an auto-regressive decoder that generates future abstraction trajectories with a per-step risk readout (localizing \emph{when} and \emph{after which events} risk rises), and a bidirectional encoder for single-pass joint risk and time-to-event prediction. Evaluated on 57,078 MIMIC-IV admissions against GRU-D, STraTS, and KarmaLego, INTERVenE-Enc reaches a support-weighted AUPRCw_w of 0.672, improving by 0.041 over the strongest neural baseline with non-overlapping 95% bootstrap CIs, while also taking the best AUROCw_w (0.901) and length-of-stay MAE (44.4,h). INTERVenE-Ar (AUROCw_w 0.8540.854, AUPRCw_w 0.5870.587 under the same evaluation contract - a strictly harder generative readout) provides a complementary token-level risk trajectory. An input-representation ablation confirms the lift transfers across structured discretizations, positioning KBTA-based intervals as the interpretable substrate that makes per-token attributions resolve to meaningful clinical concepts within the deployed model.
Aug 25, 2026cs.LG

DeMMO: Longitudinal and Cross-Disease Modelling of Digital Mobility Outcomes via Multi-Task Learning

Digital mobility outcomes (DMOs) derived from wearable sensors characterise mobility in daily life and offer a promising means of monitoring disease progression. However, existing DMO studies have typically focused on either a single disease or a single visit. To the best of our knowledge, this is the first study to systematically model and analyse longitudinal multivariate DMOs across diverse mobility-limiting diseases. Specifically, we propose DeMMO, an interpretable framework for longitudinal, multi-disease, and multi-outcome learning. DeMMO represents each disease--outcome objective using a longitudinal DMO coefficient matrix and combines temporal regularisation with stable and visit-specific feature selection. Its central technical contribution is an automatic cross-disease and cross-outcome relation-learning mechanism that infers signed relations directly from these longitudinal mappings, thereby enabling selective information sharing across cohorts without requiring paired participants. We evaluate DeMMO on the recently released, large-scale, multicentre Mobilise-D dataset, which comprises four participant-disjoint cohorts representing distinct mobility-limiting diseases, with each cohort contributing one or more clinical measurement outcomes. Compared with eight strong structural longitudinal and deep-regression baselines, DeMMO achieves the best overall predictive performance and outperforms the baselines for most individual outcomes. Stability selection further identifies reliable longitudinal DMO patterns that can inform subsequent clinical validation and disease monitoring. The implementation code is available at https://github.com/menghui-zhou/DeMMO.
Aug 13, 2026cs.LG

Intervention-Aware Clinical World Model for Post-Op Outcome Forecasting in Cardiology

Many clinical prediction models treat post-intervention outcomes as a one-step mapping from baseline measurements to a future endpoint. However, recovery after a procedure often unfolds as an irregular trajectory: clinical observations, medication changes, repeat interventions, and physiological measurements are recorded asynchronously and can change risk assessment over time. We propose an intervention-aware clinical world model that represents each patient with a structured latent state and evolves it through time-ordered post-intervention events. The model first encodes baseline imaging into a 3D spatial latent state. It then updates this state using procedural context, static covariates, elapsed time, and peri-event physiological embeddings. Follow-up imaging provides training-only supervision through a latent forecasting objective. We apply the framework to atrial fibrillation ablation. During the 90-day recovery window, irregular post-procedure records provide clinically meaningful evidence for long-term recurrence risk. In repeated internal cross-validation on DECAAF-II, our model achieves AUROC 0.756 and AUPRC 0.777 for recurrence prediction. It also achieves a scar-extent MAE of 2.971 percentage points without requiring follow-up MRI intensities at inference. The learned state supports recurrence-risk queries at different horizons and retrospective input editing of blanking-period records.
Aug 12, 2026cs.LG

Learning Under Treatment-Induced Label Indeterminacy with Expert Annotations of Counterfactual Outcomes: A Case Study in Neurological Prognostication

Clinical prediction models are often developed as if the outcome of interest were cleanly observed for every patient. This assumption fails when treatment decisions make the clinically relevant outcome permanently unobservable. As a case study of this problem, we consider post-cardiac-arrest neurological prognostication using a cohort of 2,497 patients, including 1,429 patients whose outcomes were rendered indeterminate by treatment decisions. These patients with indeterminate outcomes were reviewed by independent clinical experts, who provided their guesses of counterfactual outcomes about what would have happened to the patients. We refer to these patients as uncertain cases. We also have patients for whom we observe their clinically relevant outcomes; we refer to these patients as certain cases. We propose a framework for evaluating prediction models that explicitly splits the evaluation between certain and uncertain cases. Here, we cannot easily evaluate both types of cases in a uniform manner as the available target labels differ. We then propose a simple prediction model that uses target labels from both certain and uncertain cases in a manner that allows us to trade off between them. Across the proposed neural model and a collection of tabular baselines, models with similar certain-case AUROC can nevertheless differ substantially in both certain-case Brier score and their probability estimates for uncertain cases. Improving alignment with target labels of uncertain cases for our proposed model generally comes at the cost of worse accuracy on certain cases, highlighting an explicit tradeoff that standard evaluation conceals. These results show that when treatment decisions determine whether clinically meaningful outcomes remain observable, conventional evaluation metrics can miss important failure modes in the very patients for whom prognostic support matters most.
Aug 11, 2026cs.LG

GARLIC: Graph Attention-based Relational Learning of Multivariate Time Series in Intensive Care

Healthcare data, such as Intensive Care Unit (ICU) records, comprise heterogeneous multivariate time series sampled at irregular intervals with pervasive missingness. However, clinical applications demand predictive models that are both accurate and interpretable. We present our Graph Attention-based Relational Learning for Intensive Care (GARLIC) model, a novel neural network architecture that imputes missing data through a learnable exponential-decay encoder, captures inter-sensor dependencies via time-lagged summary graphs, and fuses global patterns with cross-dimensional sequential attention. All attention weights and graph edges are learned end-to-end to serve as built-in observation-, signal-, and edge-level explanations. To reconcile auxiliary reconstruction and primary classification objectives, we developed an alternating decoupled optimization scheme that stabilizes training. On three ICU benchmarks (PhysioNet 2012 & 2019, MIMIC-III), GARLIC sets the new state of the art in outcome prediction, significantly improving AUROC and AUPRC over best-performing baselines at comparable computational cost. Ablation studies confirm the contribution of each module, and feature-removal trials validate the fidelity of importance attribution through a monotonic performance drop (full > top 50% > random 50% > bottom 50%). Real-time case studies demonstrate actionable risk warnings with transparent explanations, marking a significant advance toward accurate, explainable deep learning for irregularly sampled ICU time series data. Moreover, we demonstrated \proposed{}'s superiority in data imputation and classification on various time-series datasets beyond the ICU domain, showing its generalizability and applicability to broader tasks.
Aug 9, 2026cs.LG

A Domain-Structured Ensemble Framework for Perioperative Outcome Prediction Using Electronic Health Record Data

Perioperative risk prediction models are often limited by narrow surgical populations, incomplete intraoperative data, poor calibration, and limited interpretability. We present a domain-structured ensemble framework for perioperative outcome prediction using routinely collected electronic health record (EHR) data. Predictors are organized into patient-related, surgery-related, and anesthetics-related domains. Domain-specific gradient boosting models generate independent risk estimates that are integrated through a logistic regression meta-learner. We demonstrate the framework using postoperative delirium (POD) in a case-control sample of 5,386 surgical encounters (2,693 cases, 2,693 controls) from a statewide health information exchange. POD required both delirium-related ICD codes and a positive Confusion Assessment Method screening within seven postoperative days; patients with preexisting dementia were excluded. The stacked meta-learner achieved AUROC 0.899 (95% CI: 0.891-0.906), precision-recall AUC 0.881, and Brier score 0.126, compared with AUROC 0.849 for the best single-stage model. Domain ablation showed improved discrimination and calibration over a surgery-only model (AUROC 0.879, Brier 0.140). Temporal validation on held-out post-2017 data yielded AUROC 0.915. Calibration was excellent, with intercept -0.006 (95% CI: -0.083 to 0.070) and slope 1.035 (95% CI: 0.982 to 1.088). Decision curve analysis, corrected for case-control sampling, showed positive net benefit across clinically plausible thresholds. The modular framework supports alternative outcomes, extension of predictor domains, and dynamic risk updating, providing a scalable foundation for interpretable, calibration-aware perioperative clinical decision support.
Aug 8, 2026cs.LG

Causal State-Space Model for Causal Inference: Estimating Longitudinal Individual Treatment Effects

Estimating counterfactual outcomes over time from longitudinal observational data is central to clinical decision support. Existing methods rely on domain confusion -- adversarial training that renders representations invariant to treatment assignment -- yet this invariance creates a mutual information conflict: it suppresses treatment-correlated covariate signals necessary for accurate outcome prediction. We formalise this tension via a Jensen-Shannon divergence bound on counterfactual prediction error and develop two complementary models. CSSD (Causal State-Space model with Direct decoder) adapts selective State Space Models with a parallel multi-step decoder that eliminates accumulated rollout error by producing all prediction horizons simultaneously in a single forward pass. CSSPD (Causal State-Space model with Predictive regularisation and Direct decoder) augments CSSD with Contrastive Predictive Coding and Local Information Maximisation to reinforce temporal predictability in the balancing representation and recover local covariate information destroyed by domain confusion. On MIMIC-III, CSSPD achieves lower counterfactual RMSE than the Causal Transformer at every horizon tau >= 2 at O(T) encoder cost, with gains from 0.02 (2-step) to 0.07 (6-step). On Cancer Simulation across confounding strengths gamma in {0,1,2,3,4}, CSSPD outperforms CT at gamma <= 3 (margins 25.9%--37.0%), and CSSD achieves the lowest overall average RMSE (12.7% reduction over CT), confirming the MI conflict analysis. To our knowledge, this is the first work to formalise the balancing-prediction MI conflict and propose a structured resolution through complementary predictive and information-theoretic training objectives.
Aug 8, 2026cs.LG

DoGMA: A Central-Dogma-Guided Foundation Model for Multi-Omics Alignment and Multi-Task Learning in Oncology

Attention mechanisms have been widely utilized in modern deep learning, and many existing multi-omics models inherit their conventional use to allow unrestricted bidirectional interactions. However, the fundamental logic of life is directional. Existing designs often overlook the directionality suggested by the central dogma, potentially limiting transfer across heterogeneous cancers, downstream tasks, and incomplete modality settings. In this work, we present DoGMA, a central-dogma-guided foundation model for pan-cancer multi-omics analysis, arguing that robust transfer requires representations with domain-specific inductive bias. Concretely, we build it on a Transformer-MoE architecture where directed attention biases inter-omics communication toward central-dogma information flow. We further pretrain our model with masked hierarchical omics reconstruction to guide it toward learning central-dogma-consistent interactions. Across diverse downstream tasks, including cancer representation learning, survival prediction, and metastasis prediction, DoGMA consistently demonstrates strong predictive performance. Ablations and analyses further suggest that the performance gains arise from the synergy between central-dogma-guided directed attention and reconstruction-based pretraining, which together promote more biologically consistent cross-omics information exchange. Overall, DoGMA demonstrates that domain-specific inductive biases can improve the robustness and transferability of multi-omics foundation models, offering new insights into the design of attention mechanisms for multi-omics representation learning.