Cildb: a knowledgebase for centrosomes and cilia

Ciliopathies, pleiotropic diseases provoked by defects in the structure or function of cilia or flagella, reflect the multiple roles of cilia during development, in stem cells, in somatic organs and germ cells. High throughput studies have revealed several hundred proteins that are involved in the composition, function or biogenesis of cilia. The corresponding genes are potential candidates for orphan ciliopathies. To study ciliary genes, model organisms are used in which particular questions on motility, sensory or developmental functions can be approached by genetics. In the course of high throughput studies of cilia in Paramecium tetraurelia, we were confronted with the problem of comparing our results with those obtained in other model organisms. We therefore developed a novel knowledgebase, Cildb, that integrates ciliary data from heterogeneous sources. Cildb links orthology relationships among 18 species to high throughput ciliary studies, and to OMIM data on human hereditary diseases. The web interface of Cildb comprises three tools, BioMart for complex queries, BLAST for sequence homology searches and GBrowse for browsing the human genome in relation to OMIM information for human diseases. Cildb can be used for interspecies comparisons, building candidate ciliary proteomes in any species, or identifying candidate ciliopathy genes. Database URL: http://cildb.cgm.cnrs-gif.fr

[1]  A. Miyawaki,et al.  Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins , 2008, Nature.

[2]  José María Carazo,et al.  CentrosomeDB: a human centrosomal proteins database , 2008, Nucleic Acids Res..

[3]  Keith A. Boroevich,et al.  Functional Genomics of the Cilium, a Sensory Organelle , 2005, Current Biology.

[4]  H. Mussaffi,et al.  DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm. , 2008, American journal of human genetics.

[5]  Edward N Pugh,et al.  The Proteome of the Mouse Photoreceptor Sensory Cilium Complex*S , 2007, Molecular & Cellular Proteomics.

[6]  Erik L. L. Sonnhammer,et al.  Inparanoid: a comprehensive database of eukaryotic orthologs , 2004, Nucleic Acids Res..

[7]  Colin A. Johnson,et al.  Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. , 2009, American journal of human genetics.

[8]  M. Brueckner,et al.  Cilia multifunctional organelles at the center of vertebrate left-right asymmetry. , 2008, Current topics in developmental biology.

[9]  Scott Cain,et al.  ParameciumDB: a community resource that integrates the Paramecium tetraurelia genome sequence with genetic data , 2006, Nucleic Acids Res..

[10]  S. Brunak,et al.  Locating proteins in the cell using TargetP, SignalP and related tools , 2007, Nature Protocols.

[11]  W. Marshall,et al.  Basal bodies platforms for building cilia. , 2008, Current topics in developmental biology.

[12]  J. Yates,et al.  New Tetrahymena basal body protein components identify basal body domain structure , 2007, The Journal of cell biology.

[13]  Jeffrey C. Smith,et al.  Robust method for proteome analysis by MS/MS using an entire translated genome: demonstration on the ciliome of Tetrahymena thermophila. , 2005, Journal of proteome research.

[14]  P. Satir,et al.  Overview of structure and function of mammalian cilia. , 2007, Annual review of physiology.

[15]  L. Ostrowski,et al.  A Proteomic Analysis of Human Cilia , 2002, Molecular & Cellular Proteomics.

[16]  M. Bornens.  Organelle positioning and cell polarity , 2008, Nature Reviews Molecular Cell Biology.

[17]  N. Katsanis,et al.  The Vertebrate Primary Cilium in Development, Homeostasis, and Disease , 2009, Cell.

[18]  Monte Westerfield,et al.  Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation , 2009, PLoS biology.

[19]  Damian Smedley,et al.  BioMart – biological queries made easy , 2009, BMC Genomics.

[20]  Shankar Subramaniam,et al.  Decoding Cilia Function Defining Specialized Genes Required for Compartmentalized Cilia Biogenesis , 2004, Cell.

[21]  Rolf Apweiler,et al.  Evaluation of methods for the prediction of membrane spanning regions , 2001, Bioinform..

[22]  R. Guigó,et al.  Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia , 2006, Nature.

[23]  J. Yates,et al.  Proteomic Analysis of Isolated Chlamydomonas Centrioles Reveals Orthologs of Ciliary-Disease Genes , 2005, Current Biology.

[24]  M. Salathe,et al.  Regulation of mammalian ciliary beating. , 2007, Annual review of physiology.

[25]  E. Bier,et al.  Accentuate the Negative:Proteome Comparisons Using the Negative Proteome Database , 2007, Fly.

[26]  P. Satir,et al.  The primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair. , 2008, Current topics in developmental biology.

[27]  G. Pazour,et al.  Proteomic analysis of a eukaryotic cilium , 2005, The Journal of cell biology.

[28]  Gary Ruvkun,et al.  Analysis of xbx genes in C. elegans , 2005, Development.

[29]  Keith A. Boroevich,et al.  Piecing together a ciliome. , 2006, Trends in genetics : TIG.

[30]  K. Gull,et al.  Flagellar motility is required for the viability of the bloodstream trypanosome , 2006, Nature.

[31]  M. Mann,et al.  Proteomic characterization of the human centrosome by protein correlation profiling , 2003, Nature.

[32]  B. Durand,et al.  Identification of novel regulatory factor X (RFX) target genes by comparative genomics in Drosophila species , 2007, Genome Biology.

[33]  S. Amselem,et al.  A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia , 2007, Proceedings of the National Academy of Sciences.

[34]  M. Brueckner,et al.  Chapter Six Cilia , 2008 .

[35]  Wallace F. Marshall,et al.  Chapter 1 Basal Bodies , 2008 .

[36]  S. Lewis,et al.  The generic genome browser: a building block for a model organism system database. , 2002, Genome research.

[37]  Tanya M. Teslovich,et al.  Comparative Genomics Identifies a Flagellar and Basal Body Proteome that Includes the BBS5 Human Disease Gene , 2004, Cell.

[38]  Aashir Awan,et al.  Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery , 2008, The Journal of cell biology.

[39]  M. Adams,et al.  Recent advances in the molecular pathology, cell biology and genetics of ciliopathies , 2008, Journal of Medical Genetics.

[40]  Adrian Gherman,et al.  The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia , 2006, Nature Genetics.

[41]  M. Cascio,et al.  Evaluation of methods for the prediction of membrane protein secondary structures. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[42]  W. Marshall,et al.  Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[43]  B. Yoder,et al.  Ciliary dysfunction in developmental abnormalities and diseases. , 2008, Current topics in developmental biology.

[44]  L. Stein,et al.  Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics , 2006, Genome Biology.

[45]  Keith Gull,et al.  Centriole/basal body morphogenesis and migration during ciliogenesis in animal cells , 2006, Journal of Cell Science.

[46]  J. Malicki,et al.  Genetic defects of pronephric cilia in zebrafish , 2007, Mechanisms of Development.

[47]  S. Frings,et al.  Proteomic analysis of a membrane preparation from rat olfactory sensory cilia. , 2007, Chemical senses.