A network-based approach to dissect the cilia/centrosome complex interactome

Background: Cilia are microtubule-based organelles protruding from almost all mammalian cells which, when dysfunctional, result in genetic disorders called "ciliopathies". High-throughput studies have revealed that cilia are composed of thousands of proteins. However, despite many efforts, much remains to be determined regarding the biological functions of this increasingly important complex organelle. Results: We have derived an online tool, from a systematic network-based approach to dissect the cilia/centrosome complex interactome (CCCI). The tool integrates all current available data into a model which provides an "interaction" perspective on ciliary function. We generated a network of interactions between human proteins organized into functionally relevant "communities", which can be defined as groups of genes that are both highly inter-connected and strongly co-expressed. We then combined sequence and co-expression data in order to identify the transcription factors responsible for regulating genes within their respective communities. Our analyses have discovered communities significantly specialized for delegating specific biological functions such as mRNA processing, protein translation, folding and degradation processes that had never been associated with ciliary proteins until now. Conclusions: CCCI will allow us to clarify the roles of previously unknown ciliary functions, elucidate the molecular mechanisms underlying ciliary-associated phenotypes, and apply our knowledge of the functional roles of relatively uncharacterized molecular entities to disease phenotypes and new clinical applications.