Network biomarker for quantifying regular state of a biological system, and dynamic network biomarker for quantifying critical state of a biological system

Abstract

We defined two new types of biomarkers to quantify the states of biological systems based on network, in contrast to the traditional molecular biomarkers. Network biomarker is constructed to quantify regular state of a biological system, while dynamic network biomarker is to quantify the critical state or tipping point of a biological system. (1) Network biomarker (NB) is a subnetwork or network module, which is composed of a number of associations or regulations between molecules (or variables), rather than simply a number of molecules. Those associations (the second-order statistics) in the module are formed collectively as a biomarker, thus robustly and accurately quantifying the regular state of a biological system, completely different from the concentrations or densities of conventional molecular biomarkers (the first-order statistics). (2) Dynamic network biomarker (DNB) is a subnetwork or module, and is also composed of a number of associations or regulations between molecules but with three statistical conditions (in terms of variances and covariances), which are actually a number of strongly and collectively fluctuated molecules in the network. Theoretically, DNB is able to quantify the critical state or the tipping point of a biological system, thereby serving as a general early-warning signal to indicate an imminent state transition. A number of real datas are provided to validate the effectiveness of NB and DNB.