Hierarchy and levels: analysing networks to study mechanisms in molecular biology.

Network representations are flat while mechanisms are organized into a hierarchy of levels, suggesting that the two are fundamentally opposed. I challenge this opposition by focusing on two aspects of the ways in which large-scale networks constructed from high-throughput data are analysed in systems biology: identifying clusters of nodes that operate as modules or mechanisms and using bio-ontologies such as gene ontology (GO) to annotate nodes with information about where entities appear in cells and the biological functions in which they participate. Of particular importance, GO organizes biological knowledge about cell components and functions hierarchically. I illustrate how this supports mechanistic interpretation of networks with two examples of network studies, one using epistatic interactions among genes to identify mechanisms and their parts and the other using deep learning to predict phenotypes. As illustrated in these examples, when network research draws upon hierarchical information such as provided by GO, the results not only can be interpreted mechanistically but provide new mechanistic knowledge. This article is part of the theme issue 'Unifying the essential concepts of biological networks: biological insights and philosophical foundations'.