Lennon J. Shikhman, Ying Qian, He Lics.LG q-bio.QM q-bio.TO
Computational models of blood clotting improve understanding of thrombus formation, but their clinical application remains limited because many model inputs are difficult to measure and patient-specific data are often sparse. We present a computational framework based on latent neural differential equations that infers unknown model parameters from sparse measurements and forecasts thrombosis progression. We demonstrate the framework using data generated from a multiphysics blood-clotting model in which clot growth is governed by the coagulation cascade and diffusion. Four known biochemical inputs (fibrinogen and factors IX, VIII, and V), together with sparse early clot-size observations, are used to infer the tissue-factor parameter and predict subsequent clot growth. We compare seven probabilistic methods: stochastic neural ordinary differential equations (SNODE), stochastic neural functional differential equations (SNFDE), a latent neural-process baseline, a monotone probabilistic deep ensemble, empirical trajectory retrieval, PCA-ridge Gaussian posterior, and Gompertz-curve retrieval. SNODE achieved the best performance in inferring the unknown input and forecasting future clot-growth trajectories. SNFDE performed similarly and consistently outperformed the other non-differential models. Prediction accuracy improved as more observations became available, whereas longer forecasting horizons increased uncertainty and decreased accuracy. Latent neural differential equations thus effectively combine parameter inference and clot-growth forecasting from sparse measurements, providing a promising foundation for personalized thrombosis modeling.
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.
Luukas Peräkylä, Fahad Sohrab, Ville Hautamäki +3cs.LG
Short-term Heart Rate Variability (HRV) forecasting could provide clinicians with actionable lead time for detecting autonomic dysfunction and adverse cardiac events. Consumer wearable devices generate fragmented, artifact-rich HRV signals that challenge conventional forecasting approaches. In this study, we evaluated the forecasting ability of three Time Series Foundation Models (TSFMs), TimesFM, Chronos, and MOIRAI, against traditional baselines (Mean, Exponential Smoothing, and Exponentially Weighted Moving Average) on real-world wearable data collected from 49 healthy individuals. To address data fragmentation, we introduce a variability-preserving imputation method that augments linear interpolation with locally adaptive stochastic noise, retaining physiological dynamics essential for accurate forecasting. The results show that TSFMs outperformed all baselines without fine-tuning, achieving average Mean Absolute Scaled Error (MASE) between 0.81 and 0.87 across TSFMs and both context lengths (32 and 64 time steps), with Chronos and TimesFM as the top models, though MOIRAI showed limited gains over baselines. With up to a 2-hour forecast horizon, the results establish a baseline for TSFMs' performance on a real-world dataset, highlighting domain-specific fine-tuning as a promising direction for clinical deployment.
Forecasting models for health-signal digital twins must preserve the oscillatory, frequency, phase, and state-transition dynamics of physiological signals, yet the pointwise metrics used to benchmark them cannot detect when these fundamental properties are lost. We show that this blind spot misranks models: across 11 architectures, models with comparable pointwise error diverge by up to 53° in phase accuracy, equivalent to roughly 123 ms for a 1.2 Hz cardiac rhythm and invisible to standard metrics. To enable development of models that escape such failures, we introduce TimeSynth, a controlled benchmarking framework with two reusable components: a physiologically grounded generator producing signals with analytically known ground-truth dynamics from parametric models fitted to real electroencephalography, electrocardiography and photoplethysmogram signals, along with diagnostics quantifying amplitude, frequency, phase, and state-transition fidelity. Linear and full-sequence attention models systematically lose frequency and phase information despite acceptable amplitude error, whereas architectures with localized temporal structure better preserve dynamical fidelity and adapt to observable state transitions; none, however, reliably preserves stochastic switching. Because the dominant determinant of fidelity is architectural, model choice becomes a principled, use-case-driven decision rather than a search for a single winner. TimeSynth thus supplies the controlled preclinical stress test missing before models are coupled to patient data, with a reusable generator and diagnostics for fidelity-aware development.