Detecting tipping points of complex diseases by network information entropy.

The progression of complex diseases often involves abrupt and non-linear changes characterized by sudden shifts that trigger critical transformations. Identifying these critical states or tipping points is crucial for understanding disease progression and developing effective interventions. To address this challenge, we have developed a model-free method named Network Information Entropy of Edges (NIEE). Leveraging dynamic network biomarkers, sample-specific networks, and information entropy theories, NIEE can detect critical states or tipping points in diverse data types, including bulk, single-sample expression data. By applying NIEE to real disease datasets, we successfully identified critical predisease stages and tipping points before disease onset. Our findings underscore NIEE's potential to enhance comprehension of complex disease development.

Detecting the Critical States of Type 2 Diabetes Mellitus Based on Degree Matrix Network Entropy by Cross-Tissue Analysis.

Type 2 diabetes mellitus (T2DM) is a metabolic disease caused by multiple etiologies, the development of which can be divided into three states: normal state, critical state/pre-disease state, and disease state. To avoid irreversible development, it is important to detect the early warning signals before the onset of T2DM. However, detecting critical states of complex diseases based on high-throughput and strongly noisy data remains a challenging task. In this study, we developed a new method, i.e., degree matrix network entropy (DMNE), to detect the critical states of T2DM based on a sample-specific network (SSN). By applying the method to the datasets of three different tissues for experiments involving T2DM in rats, the critical states were detected, and the dynamic network biomarkers (DNBs) were successfully identified. Specifically, for liver and muscle, the critical transitions occur at 4 and 16 weeks. For adipose, the critical transition is at 8 weeks. In addition, we found some "dark genes" that did not exhibit differential expression but displayed sensitivity in terms of their DMNE score, which is closely related to the progression of T2DM. The information uncovered in our study not only provides further evidence regarding the molecular mechanisms of T2DM but may also assist in the development of strategies to prevent this disease.