Differentiable latent structure discovery for interpretable forecasting in clinical time series
Authors: Ivan Lerner, Jean Feydy, Alexandre Kalimouttou, Anita Burgun, Francis Bach
Organizations: Universit´e Paris Cit´e and Universit´e Sorbonne Paris Nord, INRIA, Inserm, HEKA, Paris, 75015, France. · Department of Medical Informatics, Assistance Publique Hˆopitaux de Paris (AP-HP), Georges Pompidou European Hospital, Paris, France. · SIERRA, Inria Paris, Paris, 75015, France. · D´epartement d’Informatique de l’´Ecole Normale Sup´erieure, France. · PSL Research University, Paris, France.
Background: Timely, uncertainty-aware forecasting from irregular electronic health records (EHR) can support critical-care decisions, yet most approaches either impute to a grid or sacrifice interpretability. We introduce StructGP, a continuous-time multi-task Gaussian process that couples process convolutions with differentiable structure learning to uncover a sparse, ordered directed acyclic graph (DAG) of inter-variable dependencies while preserving principled uncertainty. We further propose LP-StructGP, which augments StructGP with latent pathways-shared, temporally shifted trajectories inferred via subject-specific coupling filters and a softmax gating mechanism-to capture cross-patient progression patterns. Both models are trained under sparsity and acyclicity constraints (augmented Lagrangian, Adam) using scalable low-rank updates. Results: In simulations, the approach reliably recovers ground-truth graphs (Structural Hamming Distance approaching 0 as cohorts grow) and pathway assignments (high Adjusted Rand Index). On a MIMIC-IV septic shock cohort (n=1,008; norepinephrine, creatinine, mean arterial pressure), StructGP improves short-horizon (6 h) forecasting over independent-task baselines (average RMSE 0.68 [95%CI: 0.63--0.74] vs. 0.88 [0.83-0.94]) and, with 15 additional inputs, markedly outperforms unstructured kernels (0.63 [0.58-0.69] vs. 3.02 [2.85-3.18]) with superior calibration (coverage 0.96 vs. 0.84). On the PhysioNet Challenge (12k patients, 41 variables), StructGP attains competitive accuracy (MAE 3.72e-2) relative to a state-of-the-art graph neural model while maintaining calibrated uncertainty. Conclusion: These results show that structured process convolutions with latent pathways deliver interpretable, scalable, and well-calibrated forecasting for irregular clinical time series.
Clinical irregular multivariate time series are shaped not only by physiological dynamics but also by the measurement process that determines when and what to observe. In event-centric models, however, co-timestamp structure can be flattened too early: measurements acquired at the same timestamp are embedded as isolated nodes, leaving local patient-state context unavailable until later message-passing layers. We study this pre-propagation representation bottleneck and address it by restoring co-timestamp context before message passing begins. We propose MissHyper, a missingness-guided hypergraph forecasting model with pre-propagation synchronicity restoration. MissHyper augments each event with a local support-density cue, aggregates co-timestamp records to recover patient-state context, and uses a missingness-guided gate to adaptively fuse node-specific evidence with the recovered context. Across PhysioNet 2012, MIMIC-III, and MIMIC-IV, MissHyper achieves consistent gains in multi-step forecasting and outperforms a strong hypergraph baseline. These results suggest that improving event initialization can benefit sparse clinical forecasting without requiring a redesigned downstream propagation architecture. Ablations indicate that snapshot restoration, adaptive fusion, and support-density encoding all contribute, pointing to event initialization as a critical design axis for sparse clinical forecasting.
Numerical time-series models can effectively process irregular electronic health record (EHR) trajectories, but they do not naturally expose the measurements and temporal patterns supporting each risk estimate as readable evidence. Existing text-based interfaces improve readability, but typically rely on either raw serialization, which is lengthy and redundant, or patient-level free-form summaries, which are difficult to trace to source measurements and time windows. To bridge this gap, we introduce TreeText-CTS (Clinical Time-Series), which converts irregular EHR trajectories into human-readable, compact, source-traceable tree-path evidence units without patient-level summarization or inference-time autoregressive decoding. TreeText-CTS routes multi-scale window summaries through frozen XGBoost models and verbalizes activated tree paths as deterministic, source-traceable evidence units composed of threshold conditions. An evidence selector assembles an informative subset of these units, which a language-model encoder then integrates for prediction. Across PhysioNet 2012 mortality, MIMIC-III mortality, and PhysioNet 2019 sepsis-onset forecasting, TreeText-CTS achieves the best AUROC and AUPRC among evaluated text-based EHR time-series interfaces, improving AUPRC by 6.0 to 9.7 absolute percentage points over the strongest prior text-based interface while remaining competitive with numerical time-series models. Ablations show that tree-path evidence construction, evidence selection, and language-model composition each contribute to performance. Because every span passed to the language-model encoder is constructed from activated tree-path threshold conditions, TreeText-CTS makes the evidence supplied to the final predictor inspectable and source-traceable.
Learning from Electronic Health Records (EHRs) has gained significant attention due to its potential to improve clinical prediction. However, effective learning remains challenging because EHRs encode heterogeneous, temporally ordered clinical interactions. In particular, EHRs contain: (i) heterogeneous clinical entities, including patients, visits, diagnoses, prescriptions, and procedures, together with their heterogeneous interactions, (ii) longitudinal patient trajectories across hospital visits and (iii) shared statistical dependencies across related clinical prediction tasks. Existing EHR learning methods capture only a subset of these properties. To bridge this gap, we propose Multi-task Graph transformer for Heterogeneous Temporal EHRs (MiGHT-EHR), which jointly models all three within a unified representation learning method. MiGHT-EHR constructs a heterogeneous graph from EHRs in which nodes represent clinical entities and edges connect statistically associated entities identified via normalized point-wise mutual information. Across MIMIC-III and MIMIC-IV datasets, MiGHT-EHR outperforms state-of-the-art methods on average across four tasks: drug recommendation, prediction of length-of-stay, mortality, and readmission, with particularly strong improvements in mortality and readmission prediction. Furthermore, a post-hoc analysis of the learned representations reveals that patient neighborhoods are organized by clinical outcomes, salient medical concepts are recoverable as linear directions in the representation space, and task probabilities are well calibrated. Collectively, these findings demonstrate that MiGHT-EHR representations support diverse prediction tasks while preserving clinically interpretable structure.