A Protein Interaction Map of Drosophila melanogaster

Abstract

Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

Probabilistic model of the human protein-protein interaction network

“…Figure 3a relates predicted interactions at various confidence levels with the GSP interactions and the estimated superset of all human protein-protein interactions. The result of nearly 40,000 predicted interactions with a false positive rate of 50% and more than 10,000 predicted interactions with a false positive rate of just 20% is comparable or superior to the results of highthroughput experimental approaches in model organisms [13][14][15][16][17][18] . To examine the validity of this model, we binned predicted interactions by LR comp and assessed the true likelihood ratios for each bin, based on the intersection with the GSP and GSN (Fig.…”

“…The S. cerevisiae interactome (SC) data comprised four high-throughput interactome data sets [13][14][15][16] and several low-throughput experiments, whereas the D. melanogaster (DM) and C. elegans (CE) data comprised one yeast two-hybrid data set each 17,18 . Human interactions were predicted by mapping model organism proteins to human orthologs using the Inparanoid database 19 (Fig.…”

Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective

“…Recent large scale interaction studies in Drosophila [220] supports the view that scaffolds can link signaling molecules to active transport mechanisms which might be an inherent property of dynamic signaling. We have briefly outlined some of these interactions in Fig.…”

“…MP1 in this context may serve to retain many regulators and effectors of Sufu in the cytoplasm and inhibit hedgehog and Wnt signaling [221]. In spite of its small size (14 kDa), MP1 has the potential to engage many systems through its interaction with Rm62 [220]. Rm62 is a putative RNA-helicase that is required for dsRNA-mediated silencing, transposon silencing and heterochromatin structure in Drosophila [222].…”

Systematic interpretation of genetic interactions using protein networks

“…For instance, direct physical interactions among proteins are being mapped by systematic two-hybrid [11][12][13][14][15] or immunoprecipitation studies 16,17 , whereas physical interactions between transcription factors and promoter sites are determined using chromatinimmunoprecipitation in conjunction with DNA microarrays 18,19 . These interactions comprise a physical network, which correlates with the network of genetic interactions and provides potential clues as to the mechanisms behind particular synthetic-lethal effects.…”