title: A network-based approach to dissect the cilia/centrosome complex interactome.
abstract: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Amato
authors.forename: Manuela
authors.initials: M
authors.lastname: Morleo
authors.forename: Laura
authors.initials: L
authors.lastname: Giaquinto
authors.forename: Diego
authors.initials: D
authors.lastname: di Bernardo
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy. franco@tigem.it.
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
mesh_terms: D018385:Centrosome / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D020407:Internet; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D014157:Transcription Factors
references.citation: Cell. 2004 May 14;117(4):527-39
references.pmid: 15137945
references.citation: Nat Genet. 2006 Jan;38(1):112-7
references.pmid: 16311594
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D175-80
references.pmid: 18971254
references.citation: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D433-7
references.pmid: 15608232
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: J Biol Chem. 2012 Sep 14;287(38):32277-87
references.pmid: 22829587
references.citation: Nat Rev Genet. 2010 May;11(5):331-44
references.pmid: 20395968
references.citation: BMC Bioinformatics. 2003 Jan 13;4:2
references.pmid: 12525261
references.citation: Am J Med Genet A. 2007 Dec 15;143A(24):3314-23
references.pmid: 17963220
references.citation: Cell. 2004 May 14;117(4):541-52
references.pmid: 15137946
references.citation: Am J Hum Genet. 2013 Nov 7;93(5):926-31
references.pmid: 24183449
references.citation: EMBO J. 2010 Oct 6;29(19):3344-57
references.pmid: 20818332
references.citation: J Clin Invest. 2014 May;124(5):2059-70
references.pmid: 24691443
references.citation: PLoS Biol. 2008 Apr 22;6(4):e98
references.pmid: 18433294
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: Dev Cell. 2008 Dec;15(6):901-12
references.pmid: 19081077
references.citation: Nat Genet. 2007 Nov;39(11):1350-60
references.pmid: 17906624
references.citation: J Cell Biol. 1999 May 3;145(3):481-90
references.pmid: 10225950
references.citation: Bioinformatics. 2006 Jul 1;22(13):1600-7
references.pmid: 16606683
references.citation: Trends Genet. 2006 Sep;22(9):491-500
references.pmid: 16860433
references.citation: EMBO J. 2004 Apr 7;23(7):1657-68
references.pmid: 15029248
references.citation: Dev Cell. 2010 Mar 16;18(3):410-24
references.pmid: 20230748
references.citation: J Cell Biol. 2008 Mar 10;180(5):897-904
references.pmid: 18332216
references.citation: Mol Cell Biol. 2004 May;24(10):4417-27
references.pmid: 15121860
references.citation: Mol Cell. 2000 Mar;5(3):411-21
references.pmid: 10882127
references.citation: Nat Genet. 2006 Sep;38(9):961-2
references.pmid: 16940995
references.citation: Commun Integr Biol. 2011 May;4(3):308-11
references.pmid: 21980565
references.citation: Genome Biol. 2006;7(12):R126
references.pmid: 17187676
references.citation: BMC Bioinformatics. 2011 Nov 09;12:436
references.pmid: 22070249
references.citation: Histochem Cell Biol. 2014 Jan;141(1):101-9
references.pmid: 23949737
references.citation: Trends Pharmacol Sci. 2010 Mar;31(3):115-23
references.pmid: 20117850
references.citation: Hum Mutat. 2010 Oct;31(10):1097-108
references.pmid: 20690115
references.citation: Curr Biol. 2005 May 24;15(10):935-41
references.pmid: 15916950
references.citation: Genome Biol. 2003;4(5):P3
references.pmid: 12734009
references.citation: Curr Biol. 2004 Jul 27;14(14):R575-7
references.pmid: 15268880
references.citation: J Proteomics. 2010 Oct 10;73(11):2277-89
references.pmid: 20637909
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6287-92
references.pmid: 16606853
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D430-6
references.pmid: 24270791
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D71-5
references.pmid: 22102590
references.citation: Nucleic Acids Res. 2011 Nov 1;39(20):8677-88
references.pmid: 21785136
references.citation: Cilia. 2013 May 31;2(1):7
references.pmid: 23725226
references.citation: Science. 1999 Oct 15;286(5439):509-12
references.pmid: 10521342
references.citation: Curr Opin Cell Biol. 2013 Aug;25(4):506-11
references.pmid: 23747070
references.citation: Mol Biol Cell. 2007 Sep;18(9):3667-80
references.pmid: 17626165
references.citation: Hum Mol Genet. 2011 Oct 15;20(R2):R149-57
references.pmid: 21862450
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D561-8
references.pmid: 21045058
references.citation: Database (Oxford). 2009;2009:bap022
references.pmid: 20428338
references.citation: Expert Rev Proteomics. 2009 Dec;6(6):647-59
references.pmid: 19929610
references.citation: Cell. 2012 Aug 3;150(3):533-48
references.pmid: 22863007
references.citation: Am J Hum Genet. 2013 Sep 5;93(3):555-60
references.pmid: 23972372
references.citation: Curr Opin Genet Dev. 2012 Jun;22(3):290-303
references.pmid: 22632799
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14621-6
references.pmid: 20679242
references.citation: Development. 2002 Dec;129(23):5487-98
references.pmid: 12403718
references.citation: Mol Biol Cell. 2007 Nov;18(11):4397-404
references.pmid: 17761535
references.citation: Biochem Biophys Res Commun. 2010 Oct 22;401(3):382-4
references.pmid: 20854791
references.citation: Biol Cell. 2010 Jul 09;102(9):499-513
references.pmid: 20690903
references.citation: Nat Genet. 2012 Jul 08;44(8):910-5
references.pmid: 22772369
references.citation: Mol Cell Proteomics. 2002 Jun;1(6):451-65
references.pmid: 12169685
references.citation: Annu Rev Immunol. 1996;14:649-83
references.pmid: 8717528