Forecasting Without Full Identification: Reliability and Computational Cost in Clot-Growth Simulation

Abstract

We forecast clot growth from sparse early measurements with incomplete biochemical information. Using 1,000 simulated trajectories, we compare inverse search, which weights candidate inputs by their agreement with early observations, with a direct multilayer perceptron (MLP) predicting future clot size. Inverse search is more accurate when tissue factor alone, or tissue factor and fibrinogen, are unknown. When all five inputs are unknown, direct prediction achieves 2.16% pooled relative $L_2$ forecast error, outperforming search with 8,192 candidates using a forward MLP (3.25%) or latent neural ordinary differential equation model (3.36%). A conditional error bound separates candidate disagreement, weight on poor early fits, surrogate error, and candidate coverage. Increasing randomized quasi-Monte Carlo candidate budgets from 512 to 32,768 reduces numerical variation. A covariance score ranks additional assays by expected forecast value while accounting for measurement noise. At 10% range-scaled assay noise, incorporating assay uncertainty reduces forecast error from about 5% to below 3% for both surrogates. An independent reaction cascade verifies candidate integration against tensor quadrature, with mean normalized forecast-integration error below $10^{-5}$ at 32,768 candidates. These results demonstrate accurate clot-growth forecasting without full biochemical identification and support selecting prediction strategies and additional measurements according to accuracy, reliability, and computational cost.