Disentangling Interactions in the Microbiome: A Network Perspective

Abstract

Microbiota are now widely recognized as being central players in the health of all organisms and ecosystems, and subsequently have been the subject of intense study. However, analyzing and converting microbiome data into meaningful biological insights remain very challenging. In this review, we highlight recent advances in network theory and their applicability to microbiome research. We discuss emerging graph theoretical concepts and approaches used in other research disciplines and demonstrate how they are well suited for enhancing our understanding of the higher-order interactions that occur within microbiomes. Network-based analytical approaches have the potential to help disentangle complex polymicrobial and microbe-host interactions, and thereby further the applicability of microbiome research to personalized medicine, public health, environmental and industrial applications, and agriculture.

Keywords: keystone species; microbial clusters; microbial interactions; microbiome; network.

Figure I

Four Main Types of Network. The top panel shows the network representations of the four main types, each consisting of 100 nodes. The middle panel shows the same networks in a circular layout to accentuate the differences between the network types. The bottom panel shows plots of two node centrality measures as well as the degree distribution for each of the above networks (all measurements are standardized). (A) Regular network: each node has exactly the same number of links. (B) Random network: nodes are randomly connected to each other. (C) Small-world network: most nodes can be reached from any other node through a short path. (D) Scale-free network: the degree distribution of nodes follows a power law.

Figure 1

Key Figure: Microbiome Network Analysis (A) A microbiome network built from an OTU table. Each blue node represents a microbe from the microbiome, and each gray link represents a pairwise co-occurrence or interaction. (B) The same microbiome network with nodes’ sizes proportionate to HITS scores computed for all the microbes. (C) The same microbiome network with hub (keystone) species highlighted in red. (D) The same microbiome network with microbes clustered into five distinct groups.