Integrating the interactome and the transcriptome of Drosophila

Networks of interacting genes and gene products mediate most cellular and developmental processes. High throughput screening methods combined with literature curation are identifying many of the protein-protein interactions (PPI) and protein-DNA interactions (PDI) that constitute these networks. Most of the detection methods, however, fail to identify the in vivo spatial or temporal context of the interactions. Thus, the interaction data are a composite of the individual networks that may operate in specific tissues or developmental stages. Genome-wide expression data may be useful for filtering interaction data to identify the subnetworks that operate in specific spatial or temporal contexts. Here we take advantage of the extensive interaction and expression data available for Drosophila to analyze how interaction networks may be unique to specific tissues and developmental stages.

We ranked genes on a scale from ubiquitously expressed to tissue or stage specific and examined their interaction patterns. Interestingly, ubiquitously expressed genes have many more interactions among themselves than do non-ubiquitously expressed genes both in PPI and PDI networks. While the PDI network is enriched for interactions between tissue-specific transcription factors and their tissue-specific targets, a preponderance of the PDI interactions are between ubiquitous and non-ubiquitously expressed genes and proteins. In contrast to PDI, PPI networks are depleted for interactions among tissue- or stage- specific proteins, which instead interact primarily with widely expressed proteins. In light of these findings, we present an approach to filter interaction data based on gene expression levels normalized across tissues or developmental stages. We show that this filter (the percent maximum or pmax filter) can be used to identify subnetworks that function within individual tissues or developmental stages.

These observations suggest that protein networks are frequently organized into hubs of widely expressed proteins to which are attached various tissue- or stage-specific proteins. This is consistent with earlier analyses of human PPI data and suggests a similar organization of interaction networks across species. This organization implies that tissue or stage specific networks can be best identified from interactome data by using filters designed to include both ubiquitously expressed and specifically expressed genes and proteins.