CiliaCarta: An integrated and validated compendium of ciliary genes

6533b7d6fe1ef96bd1266fed

RESEARCH PRODUCT

CiliaCarta: An integrated and validated compendium of ciliary genes

Gerard W. Dougherty Victor L. Jensen Jan Frederik Scheel Katarzyna Szymanska Uwe Wolfrum Radek Szklarczyk Miriam Schmidts Julie Kennedy Erwin Van Wijk Brunella Franco Toby J. Gibson Machteld M. Oud Chunmei Li Nils J. Lambacher Nils J. Lambacher Erik De Vrieze Grischa Toedt Teunis J. P. Van Dam Teunis J. P. Van Dam Karsten Boldt Heymut Omran Yves Texier Rachel H. Giles Ronald Roepman Kirsten A. Wunderlich Sylvia E. C. Van Beersum Oliver E. Blacque Thanh-minh T. Nguyen Konstantinos Koutroumpas Hannie Kremer Nicola Horn Martijn A. Huynen Michel R. Leroux Gabrielle Wheway Rim Hjeij Philip L. Beales Gisela G. Slaats Robert B. Russell Robin Van Der Lee François Képès Yasmin Wissinger Barbara Knapp Dorus A. Mans Suzanne Rix Marius Ueffing Colin A. Johnson Stef J.f. Letteboer Victor Hernandez-hernandez Qianhao Lu Jeroen Van Reeuwijk

subject

Proteomics Sensory Receptors Nematoda Social Sciences Ciliopathies Biochemistry Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Transcriptome 0302 clinical medicine Animal Cells Psychology RETINAL PHOTORECEPTOR CELLS Exome Neurons 0303 health sciences 030302 biochemistry & molecular biology Eukaryota Genomics PRIMARY CILIUM thecilium 3. Good health Nucleic acids Genetic interference Osteichthyes Medicine Epigenetics Cellular Structures and Organelles Cellular Types proteomic databases Sensory Receptor Cells Science education Ciliary genes LEBER CONGENITAL AMAUROSIS Genomics 03 medical and health sciences Genetics Cilia Caenorhabditis elegans IDENTIFICATION MUTATIONS Embryos cilia Organisms Biology and Life Sciences Bayes Theorem Molecular Sequence Annotation medicine.disease Invertebrates Fish ciliary proteome Animal Studies Caenorhabditis Gene expression embryos 030217 neurology & neurosurgery Developmental Biology Neuroscience Photoreceptors Candidate gene Embryology Oligonucleotides Morpholino Database and Informatics Methods RNA interference Bayesian classifier TRANSITION ZONE Zebrafish Antisense Oligonucleotides Zebrafish Genetics Multidisciplinary Spectrometric Identification of Proteins Proteomic Databases Nucleotides Cilium Q Stable Isotope Labeling by Amino Acids in Cell Culture R photoreceptors Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]Animal Models Phenotype INTRAFLAGELLAR TRANSPORT DIFFERENTIATION Phenotype Experimental Organism Systems Caenorhabditis Elegans Vertebrates Sensory Perception Research Article Signal Transduction EXPRESSION Stable isotope labeling by amino acids in cell culture Computational biology Biology Research and Analysis Methods SOLUTE-CARRIER-PROTEIN Model Organisms medicine Animals data integration 030304 developmental biology Afferent Neurons Reproducibility of Results Cell Biology zebrafish biology.organism_classification Ciliopathy Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]Biological Databases Cellular Neuroscience RNA OSCP1 CiliaCarta

description

The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse, zebrafish and nematode) and techniques. For example, we show that OSCP1, which has previously been implicated in two distinct non-ciliary processes, causes ciliogenic and ciliopathy-associated tissue phenotypes when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 956 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/. This work was supported by the European Community’s Seventh Framework Programme [241955, 278568 to MU and KB, 602273 to RS]; the Virgo consortium, funded by the Dutch government [FES0908 to TvD, RvdL and MAH]; the Netherlands Genomics Initiative [050-060-452 to TvD, RvdL and MAH]; the Canadian Institutes of Health Research [MOP-142243, MOP-82870 and PJT-156042 to MRL]; Michael Smith Foundation for Health Research to MRL and VLJ; Kidney Research Scientist Core Education and National Training fellowship to VLJ; The Foundation Fighting Blindness [PPA-0717-0719-RAD to UW, RR, and MU]; the Dutch Kidney Foundation “KOUNCIL” consortium [CP11.18 to RHG, PLB and RR]; The Deutsche Forschungsgemeinschaft [Excellence grant CellNetworks to RBR and QL, CRC1140 “Kidney Disease – From Genes to Mechanisms” to MS, collaborative research center grant SFB-1411 KIDGEM to MS]; Metakids Foundation to RS; the National Institute for Health Research to PLB and VH-H. PLB is an NIHR Senior Investigator; Radboudumc Hypatia Tenure Track Fellowship, Radboud Universiteit excellence fellowship, ERC starting grant TREATCilia, grant agreement no. 716344 to MS; and the Netherlands Organization for Scientific Research [NWO Vici-865.12.005 to RR].

year	journal	country	edition	language
2019-05-16	PLoS ONE

10.1371/journal.pone.0216705 http://europepmc.org/articles/PMC6522010