Supplemental Material and Methods For: Finding New Order in Biological Functions from the Network Structure of Gene Annotations

In this section we provide additional materials meant to complement and expand upon the analysis in “Finding New Order in Biological Functions from the Network Structure of Gene Annotations.” In the first section, “Enrichment of Term-Network Edges in Known CrossDomain Relationships”, we compare edges predicted in our network model to documented relationships in the Gene Ontology that extend between terms in different primary domains. In the second section, “Communities Found Across Multiple Resolutions”, we provide more detail about how we used the resolution parameter to generate multiple, overlapping, yet unique communities of terms. In the third section, “Domain-specific Analysis” we provide analysis of communities of terms compared to branches within each primary domain of GO. Next, in “Visualizing GO Branches” we illustrate relationships between GO branches at different “levels” of the GO DAG. In the section entitled “Functional Enrichment Analysis”, we briefly explain the methodology used to evaluate the statistical enrichment of gene sets in the term communities and GO branches, and provide analysis showing that, as desired, this enrichment is absent for randomly generated term communities or randomly generated sets of genes. Finally, in “Comparative Species Analysis” we construct and analyze annotation-driven term networks using gene annotations for seventeen additional organisms and compare those networks with each other as well as the human results presented in the main text. For information regarding the methodology used to illustrate the term communities or generate the word clouds in the main text, see Section 2, “Supplemental Methods’.’