Considerable evidence suggests that during the progression of complex diseases, the deteriorations are not necessarily smooth but are abrupt, and may cause a critical transition from one state to another at a tipping point. Here, we develop a model-free method to detect early-warning signals of such critical transitions (un-occurred diseases), even with only a small number of samples. 

Specifically, we theoretically derive an index based on a dynamic network biomarker (DNB) that serves as a general early-warning signal indicating an imminent sudden deterioration before the critical transition occurs [1][2]. Based on theoretical analyses, we show that predicting a sudden transition from small samples is achievable provided that there are a large number of measurements for each sample, e.g., high-throughput data. 

We employ gene expression data of three diseases to demonstrate the effectiveness of our method for predictive and preventive medicine. The relevance of DNBs with the diseases was also validated by related experimental data (e.g., liver cancer, lung injury, influenza, type-2 diabetes) and functional analysis. DNB can also be used for the analysis of nonlinear biological processes.