The P/N (Positive-to-Negative Links) Ratio in Complex Networks-A Promising In Silico Biomarker for Detecting Changes Occurring in the Human Microbiome

Relatively little progress in the methodology for differentiating between the healthy and diseased microbiomes, beyond comparing microbial community diversities with traditional species richness or Shannon index, has been made. Network analysis has increasingly been called for the task, but most currently available microbiome datasets only allows for the construction of simple species correlation networks (SCNs). The main results from SCN analysis are a series of network properties such as network degree and modularity, but the metrics for these network properties often produce inconsistent evidence. We propose a simple new network property, the P/N ratio, defined as the ratio of positive links to the number of negative links in the microbial SCN. We postulate that the P/N ratio should reflect the balance between facilitative and inhibitive interactions among microbial species, possibly one of the most important changes occurring in diseased microbiome. We tested our hypothesis with five datasets representing five major human microbiome sites and discovered that the P/N ratio exhibits contrasting differences between healthy and diseased microbiomes and may be harnessed as an in silico biomarker for detecting disease-associated changes in the human microbiome, and may play an important role in personalized diagnosis of the human microbiome-associated diseases.