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A network-based approach to dissect the cilia/centrosome complex interactome
© Morleo et al. 2015
Published: 13 July 2015
We built a network of curated interactions between human proteins involved with centrioles, centrosomes, basal bodies and cilia to provide a global functional characterization of the Cilia/Centrosome Complex interactome (CCCI).
Human ciliary genes were collected from available databases and interactions among genes were obtained from the STRING database (http://string-db.org). Network analyses were performed using Cytoscape and communities were extracted using the MCODE algorithm. The gene-wise network was explored by Gene Ontology (GO) analysis. The transcription factor (TF) analysis was performed using information obtained from "ConsSites" and "tfbsConsFactors" track of the UCSC Genome Browser.
We collected 3,502 ciliary genes and obtained the final CCCI, which consisted of 11,608 interactions among 1,695 selected genes. We identified 90 communities, groups of genes densely interconnected with each other and connected to few genes outside the group. We discovered communities specialized for delegating specific biological functions such as mRNA processing, protein translation, folding and degradation processes. In particular the "proteasome community" was enriched in ciliary components belonging to the SYSCILIA Gold Standard (SCGSv1) and in ciliopathy genes. We found 11 communities enriched in 30 TFs. The identified TFs are involved in developmental processes, cell cycle control, in the immune response and in muscle differentiation.
CCCI is a publically available tool, which will allow to clarify the roles of previously unknown ciliary functions and to elucidate the molecular mechanisms underlying ciliary-associated phenotypes.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.