Identifying the critical states and dynamic network biomarkers of cancers based on network entropy

• Published in: Journal of translational medicine Vol. 20; no. 1; pp. 254 - 13
• Main Authors: Liu, Juntan, Ding, Dandan, Zhong, Jiayuan, Liu, Rui
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.06.2022; BioMed Central; BMC
• Subjects: Biological markers; Biomarkers; Biomarkers - metabolism; Cancer; Computer applications; Critical state; Critical transition; Datasets; Diagnosis; Disease; Disease Progression; Dynamic network biomarker (DNB); Entropy; Gene expression; Genetic aspects; Health aspects; Humans; Local network entropy (LNE); Lymphatic system; Metastasis; Neoplasms - diagnosis; Nonlinear systems; Oncology, Experimental; Phase transitions; Pre-disease state; Prevention; Prognostic biomarker; Proteins; Tumor necrosis factor-TNF; China; Critical state; Critical transition; Pre-disease state; Dynamic network biomarker (DNB); Local network entropy (LNE); Prognostic biomarker
• DOI: 10.1186/s12967-022-03445-0
• ISSN: 1479-5876

There are sudden deterioration phenomena during the progression of many complex diseases, including most cancers; that is, the biological system may go through a critical transition from one stable state (the normal state) to another (the disease state). It is of great importance to predict this critical transition or the so-called pre-disease state so that patients can receive appropriate and timely medical care. In practice, however, this critical transition is usually difficult to identify due to the high nonlinearity and complexity of biological systems. In this study, we employed a model-free computational method, local network entropy (LNE), to identify the critical transition/pre-disease states of complex diseases. From a network perspective, this method effectively explores the key associations among biomolecules and captures their dynamic abnormalities. Based on LNE, the pre-disease states of ten cancers were successfully detected. Two types of new prognostic biomarkers, optimistic LNE (O-LNE) and pessimistic LNE (P-LNE) biomarkers, were identified, enabling identification of the pre-disease state and evaluation of prognosis. In addition, LNE helps to find "dark genes" with nondifferential gene expression but differential LNE values. The proposed method effectively identified the critical transition states of complex diseases at the single-sample level. Our study not only identified the critical transition states of ten cancers but also provides two types of new prognostic biomarkers, O-LNE and P-LNE biomarkers, for further practical application. The method in this study therefore has great potential in personalized disease diagnosis.