Abstract
The progression of complex human diseases is associated with critical transitions across dynamical regimes. These transitions often spawn early-warning signals and provide insights into the underlying disease-driving mechanisms. In this paper, we propose a computational method based on surprise loss (SL) to discover data-driven indicators of such transitions in a multivariate time series dataset of septic shock and non-sepsis patient cohorts (MIMIC-III database). The core idea of SL is to train a mathematical model on time series in an unsupervised fashion and to quantify the deterioration of the model’s forecast (out-of-sample) performance relative to its past (in-sample) performance. Considering the highest value of the moving average of SL as a critical transition, our retrospective analysis revealed that critical transitions occurred at a median of over 35 hours before the onset of septic shock, which suggests the applicability of our method as an early-warning indicator. Furthermore, we show that clinical variables at critical-transition regions are significantly different between septic shock and non-sepsis cohorts. Therefore, our paper contributes a critical-transition-based data-sampling strategy that can be utilized for further analysis, such as patient classification. Moreover, our method outperformed other indicators of critical transition in complex systems, such as temporal autocorrelation and variance.
Highlights
Certain biological systems exhibit nonlinear dynamics that undergo sudden regime transitions at tipping points[1,2]
We present a critical-transition-based data-sampling strategy is presented where data are sampled at regions around critical transition; this strategy outperforms random sampling in differentiation between septic shock and non-sepsis patients
Software implementations with different data cleaning processes and patient exclusion criteria (PEC) from the same annotation framework could result in divergent cohorts
Summary
Data-driven methods use statistical indicators known as early-warning signals to model the dynamics of systems approaching transitions[7,8,9,10,11,12,13,14]. Modeling such transitions is beneficial for several applications in systems medicine, such as monitoring health[15,16], predicting disease-onset and gaining an improved understanding of the underlying disease progression[17]. We compare our approach to methods based on autocorrelation and variance[7,15,16,35], which have been used to identify early-warning signals of critical transitions
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