Individual-specific edge-network analysis for disease prediction.

Predicting pre-disease state or tipping point just before irreversible deterioration of health is a difficult task. Edge-network analysis (ENA) with dynamic network biomarker (DNB) theory opens a new way to study this problem by exploring rich dynamical and high-dimensional information of omics data. Although theoretically ENA has the ability to identify the pre-disease state during the disease progression, it requires multiple samples for such prediction on each individual, which are generally not available in clinical practice, thus limiting its applications in personalized medicine. In this work to overcome this problem, we propose the individual-specific ENA (iENA) with DNB to identify the pre-disease state of each individual in a single-sample manner. In particular, iENA can identify individual-specific biomarkers for the disease prediction, in addition to the traditional disease diagnosis. To demonstrate the effectiveness, iENA was applied to the analysis on omics data of H3N2 cohorts and successfully detected early-warning signals of the influenza infection for each individual both on the occurred time and event in an accurate manner, which actually achieves the AUC larger than 0.9. iENA not only found the new individual-specific biomarkers but also recovered the common biomarkers of influenza infection reported from previous works. In addition, iENA also detected the critical stages of multiple cancers with significant edge-biomarkers, which were further validated by survival analysis on both TCGA data and other independent data.