Statistical Methods for Microbiome Compositional Data Network Inference: A Survey.

Microbes can be found almost everywhere in the world. They are not isolated, but rather interact with each other and establish connections with their living environments. Studying these interactions is essential to an understanding of the organization and complex interplay of microbial communities, as well as the structure and dynamics of various ecosystems. A widely used approach toward this objective involves the inference of microbiome interaction networks. However, owing to the compositional, high-dimensional, sparse, and heterogeneous nature of observed microbial data, applying network inference methods to estimate their associations is challenging. In addition, external environmental interference and biological concerns also make it more difficult to deal with the network inference. In this article, we provide a comprehensive review of emerging microbiome interaction network inference methods. According to various research targets, estimated networks are divided into four main categories: correlation networks, conditional correlation networks, mixture networks, and differential networks. Their assumptions, high-level ideas, advantages, as well as limitations, are presented in this review. Since real microbial interactions can be complex and dynamic, no unifying method has, to date, captured all the aspects of interest. In addition, we discuss the challenges now confronting current microbial interaction study and future prospects. Finally, we point out several feasible directions of microbial network inference analysis and highlight that future research requires the joint promotion of statistical computation methods and experimental techniques.