Figure 4

Co-occurrence network analysis with the ReBoot algorithm reveals novel community interactions in EAE. (A) Color-coded network graph representations of the co-occurrence and mutual exclusion interactions among ASVs. White numbers within nodes correspond to numbering in the legend. Transparent shapes represent network communities determined by the Louvain modularity algorithm. Black numbering corresponds to the numbering given to distinguish communities within each network. (B) Schematic representing the process for calculating taxonomic over-representation with respect to the nodes and edges within a community. Networks are split by community membership and tested for over-representation of all taxa and all unique taxa-taxa pairings within the community of interest. Fisher’s exact test is applied on two-way contingency tables that distinguish nodes by community membership and taxonomic membership. Testing framework is performed independently for each network. (C) Heatmap of BH-adjusted P-values for over-representation of unique edges among the communities of each co-occurrence network. Each row represents a unique edge connecting two distinct families. Each column is a community in one of the three networks. Cell color corresponds to edge frequency within each network and each cell contains an edge frequency number followed by a significance level in parentheses (Blank = n.s., *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001). Heatmap has been filtered to only contain edges of interest and communities with at least one significant P-value among these edges. Grey cells represent edges that were entirely absent from the network they appear under. Columns represent unique communities in each network. (D) Heatmap representing BH-adjusted P-values for over-representation of unique edges among the communities of each mutual exclusion network following the same construction methods and conventions as (B). Columns represent unique communities in each network. The manually selected edges of interest are different from those in (C).