Medical ecology and network analyses for the human vaginal virome

The human vaginal virome (HVV) is an integral yet understudied component of the human vaginal microbiome (HVM). While much research on the HVM has focused on bacterial communities, this study shifts attention to the HVV by computationally extracting virome data from a large metagenomic dataset of the HVM[ 19 ], Nature Communications). We generated a comprehensive HVV dataset comprising 703 viral species across 1,464 samples. To uncover ecological and structural insights, we applied a suite of medical ecology and network analyses, including diversity, heterogeneity, stochasticity, core/periphery network structure, network diversity, and network heterogeneity. Beyond establishing baseline ecological and network metrics for a healthy female cohort, our analyses yielded several key findings: (i) Diversity and heterogeneity are driven by factors operating on different temporal scales, with species interactions shaping heterogeneity over evolutionary time and abundance fluctuations influencing diversity on ecological time scales. (ii) Both stochastic neutrality and deterministic forces, such as host physiology and genetics, significantly influence virome dynamics, as evidenced by approximately 49 % neutral species and 41 % positively selected (above-neutral) species. (iii) The HVV network exhibits a core/periphery structure, with densely connected core species and sparsely connected periphery species, characterized by moderate strength (Rho = 0.467) and a high positive-to-negative interaction ratio (P/N = 5.4), indicating predominantly cooperative species interactions. (iv) Network diversity and heterogeneity were assessed using advanced methodologies, including Taylor’s Power Law of Networks (TPLoN). (v) A small number of key viral species were identified, collectively constituting over 80 % of the virome composition, and their biomedical significance was evaluated based on existing literature. These findings provide critical insights into the ecological processes shaping the vaginal virome, emphasizing the interplay of stochastic and deterministic forces. They also lay a foundation for understanding viral community dynamics and their implications for host health and microbial interactions.