Detection for disease tipping points by landscape dynamic network biomarkers

• 作者: Hui Tang Kazuyuki Aihara Luonan Chen Siyang Leng Xiao Chang Xiaoping Liu
• 来源期刊: 国家科学评论（英文版）
• 年，卷（期）: 2019,（4）
• 页码范围: 775-785
• 页数: 11页
• 语种: 英文
• DOI: 10.1093/nsr/nwy162

摘要

A new model-free method has been developed and termed the landscape dynamic network biomarker (l-DNB) methodology. The method is based on bifurcation theory, which can identify tipping points prior to serious disease deterioration using only single-sample omics data. Here, we show that l-DNB provides early-warning signals of disease deterioration on a single-sample basis and also detects critical genes or network biomarkers (i.e. DNB members) that promote the transition from normal to disease states. As a case study, l-DNB was used to predict severe in fluenza symptoms prior to the actual symptomatic appearance in in fluenza virus infections. The l-DNB approach was then also applied to three tumor disease datasets from the TCGA and was used to detect critical stages prior to tumor deterioration using an individual DNB for each patient. The individual DNBs were further used as individual biomarkers in the analysis of physiological data, which led to the identification of two biomarker types that were surprisingly effective in predicting the prognosis of tumors. The biomarkers can be considered as common biomarkers for cancer, wherein one indicates a poor prognosis and the other indicates a good prognosis.