Figure 1

Disease stages and disease biomarkers. A). three stages during disease progression, i.e., normal state, pre-disease state and disease state. A normal state is a relatively healthy stage including the chronic inflammation period or the period during which the disease is under control, whereas a pre-disease state is the limit of the normal state just before the critical transition of the disease. At this stage, the pre-disease state is considered to be reversible to the normal state if appropriately treated. However, if the system passes over the critical point to the disease state, it usually becomes very difficult irreversibly to the normal state. B). Traditional biomarkers are indicators on the disease state and static measurements on the disease, and can distinguish disease samples from normal. C). The dynamical network biomarkers (DNBs) are signal of the pre-disease state and dynamical measurements on the pre-disease, and can distinguish pre-disease samples from normal samples, thus providing the early-warning signals for the pre-disease state.