Active Interaction Mapping as a tool to elucidate hierarchical functions of biological processes

Increasingly, various 'omics data are contributing significantly to our understanding of novel biological processes, but it has not been possible to iteratively elucidate hierarchical functions in complex phenomena. We describe a general systems biology approach called Active Interaction Mapping (AI-MAP), which elucidates the hierarchy of functions for any biological process. Existing and new 'omics data sets can be iteratively added to create and improve hierarchical models which enhance our understanding of particular biological processes. The best datatypes to further improve an AI-MAP model are predicted computationally. We applied this approach to our understanding of general and selective autophagy, which are conserved in most eukaryotes, setting the stage for the broader application to other cellular processes of interest. In the particular application to autophagy-related processes, we uncovered and validated new autophagy and autophagy-related processes, expanded known autophagy processes with new components, integrated known non-autophagic processes with autophagy and predict other unexplored connections.