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SymPerturb converts symptom-network structure into testable intervention priorities

Zhu, Z.; Yu, J.; Hu, T.; Yang, Z.; Wang, J.

2026-07-30 epidemiology
10.64898/2026.07.27.26359002 medRxiv
Show abstract

Symptom networks encode conditional dependence but do not by themselves identify causal or clinically actionable intervention targets. We introduce SymPerturb, a virtual-perturbation framework that distinguishes four primitive perturbation operators - virtual knockout, virtual knockdown, edge-level communication blocking and node-centred communication blocking - from three analytic procedures - virtual dosage perturbation, combination perturbation and sequence optimisation. The reference Gaussian implementation is embedded in a general location-scale map with symptom-specific target anchors, making explicit that zero anchoring and linked mean-variance attenuation are modelling choices. Seven utility outcomes quantify downstream efficacy, dose efficiency, breadth, cross-module reach, communication blocking, combination value and responsiveness; robustness is reported separately as an uncertainty diagnostic. Their direction-aligned, within-candidate-set weighted mean defines the virtual perturbation priority score (VPPS), which is a relative ranking rather than a transportable clinical utility score. In a known 22-node, four-module generating network, analytical efficacy agreed with 100,000-draw Monte Carlo estimates within 0.0024 standard deviations. The reported finite-sample VPPS results were generated with the original eight-component exploratory score and therefore require regeneration under the revised seven-utility-dimension definition. These simulations provide internal computational verification under model compatibility, not causal or external validation. SymPerturb is intended to generate auditable target hypotheses for longitudinal and experimental testing.

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