CiliaCarta: An integrated and validated compendium of ciliary genes

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

doi:10.1371/journal.pone.0216705

CiliaCarta: An integrated and validated compendium of ciliary genes

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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/.

Original language	English
Article number	0216705
Number of pages	32
Journal	PLOS ONE
Volume	14
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0216705
Publication status	Published - 16 May 2019

Keywords

DIFFERENTIATION
EXPRESSION
IDENTIFICATION
INTRAFLAGELLAR TRANSPORT
LEBER CONGENITAL AMAUROSIS
MUTATIONS
PRIMARY CILIUM
RETINAL PHOTORECEPTOR CELLS
SOLUTE-CARRIER-PROTEIN
TRANSITION ZONE

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van Dam, T. J. P., Kennedy, J., van der Lee, R., de Vrieze, E., Wunderlich, K. A., Rix, S., Dougherty, G. W., Lambacher, N. J., Li, C., Jensen, V. L., Leroux, M. R., Hjeij, R., Horn, N., Texier, Y., Wissinger, Y., van Reeuwijk, J., Wheway, G., Knapp, B., Scheel, J. F., ... Huynen, M. A. (2019). CiliaCarta: An integrated and validated compendium of ciliary genes. PLOS ONE, 14(5), Article 0216705. https://doi.org/10.1371/journal.pone.0216705

@article{5ab8bbdbfc69472d97bd9753933ba6ea,

title = "CiliaCarta: An integrated and validated compendium of ciliary genes",

abstract = "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/.",

keywords = "DIFFERENTIATION, EXPRESSION, IDENTIFICATION, INTRAFLAGELLAR TRANSPORT, LEBER CONGENITAL AMAUROSIS, MUTATIONS, PRIMARY CILIUM, RETINAL PHOTORECEPTOR CELLS, SOLUTE-CARRIER-PROTEIN, TRANSITION ZONE",

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

note = "Funding Information: This work was supported by the European Community{\textquoteright}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]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We kindly acknowledge Prof. Dr. N. Katsanis and J. R. Willer from Duke University USA for providing several of the clone constructs used as baits in the SILAC and Y2H data sets. We also thank the Caenorhabditis elegans Genetics Center (Minnesota, USA), the National Bioresource project (Tokyo, Japan), the International C. elegans gene knockout consortium, and the C. elegans Million Mutation Project for nematode reagents. We thank Emine Bolat, Ideke Lamers, Mon-iek Riemersma, and Karlien Coene for performing yeast two-hybrid and SILAC experiments. Funding Information: InstitutesofHealthResearch[MOP-142243,MOP-82870andPJT-156042toMRL];MichaelSmith FoundationforHealthResearchtoMRLandVLJ; KidneyResearchScientistCoreEducationand NationalTrainingfellowshiptoVLJ;TheFoundation FightingBlindness[PPA-0717-0719-RADtoUW, RR,andMU];theDutchKidneyFoundation “KOUNCIL”consortium[CP11.18toRHG,PLBand RR];TheDeutscheForschungsgemeinschaft [ExcellencegrantCellNetworkstoRBRandQL, CRC1140“KidneyDisease–FromGenesto Mechanisms”toMS,collaborativeresearchcenter grantSFB-1411KIDGEMtoMS];Metakids FoundationtoRS;theNationalInstituteforHealth ResearchtoPLBandVH-H.PLBisanNIHRSenior Investigator;RadboudumcHypatiaTenureTrack Fellowship,RadboudUniversiteitexcellence fellowship,ERCstartinggrantTREATCilia,grant agreementno.716344toMS;andtheNetherlands OrganizationforScientificResearch[NWOVici-865.12.005toRR].Thefundershadnorolein studydesign,datacollectionandanalysis,decision topublish,orpreparationofthemanuscript. Publisher Copyright: {\textcopyright} 2019 van Dam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2019",

month = may,

day = "16",

doi = "10.1371/journal.pone.0216705",

language = "English",

volume = "14",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

van Dam, TJP, Kennedy, J, van der Lee, R, de Vrieze, E, Wunderlich, KA, Rix, S, Dougherty, GW, Lambacher, NJ, Li, C, Jensen, VL, Leroux, MR, Hjeij, R, Horn, N, Texier, Y, Wissinger, Y, van Reeuwijk, J, Wheway, G, Knapp, B, Scheel, JF, Franco, B, Mans, DA, van Wijk, E, Kepes, F, Slaats, GG, Toedt, G, Kremer, H, Omran, H, Szymanska, K, Koutroumpas, K, Ueffing, M, Nguyen, T-MT, Letteboer, SJF, Oud, MM, van Beersum, SEC, Schmidts, M, Beales, PL, Lu, Q, Giles, RH, Szklarczyk, R, Russell, RB, Gibson, TJ, Johnson, CA, Blacque, OE, Wolfrum, U, Boldt, K, Roepman, R, Hernandez-Hernandez, V & Huynen, MA 2019, 'CiliaCarta: An integrated and validated compendium of ciliary genes', PLOS ONE, vol. 14, no. 5, 0216705. https://doi.org/10.1371/journal.pone.0216705

TY - JOUR

T1 - CiliaCarta

T2 - An integrated and validated compendium of ciliary genes

AU - van Dam, Teunis J. P.

AU - Kennedy, Julie

AU - van der Lee, Robin

AU - de Vrieze, Erik

AU - Wunderlich, Kirsten A.

AU - Rix, Suzanne

AU - Dougherty, Gerard W.

AU - Lambacher, Nils J.

AU - Li, Chunmei

AU - Jensen, Victor L.

AU - Leroux, Michel R.

AU - Hjeij, Rim

AU - Horn, Nicola

AU - Texier, Yves

AU - Wissinger, Yasmin

AU - van Reeuwijk, Jeroen

AU - Wheway, Gabrielle

AU - Knapp, Barbara

AU - Scheel, Jan F.

AU - Franco, Brunella

AU - Mans, Dorus A.

AU - van Wijk, Erwin

AU - Kepes, Francois

AU - Slaats, Gisela G.

AU - Toedt, Grischa

AU - Kremer, Hannie

AU - Omran, Heymut

AU - Szymanska, Katarzyna

AU - Koutroumpas, Konstantinos

AU - Ueffing, Marius

AU - Nguyen, Thanh-Minh T.

AU - Letteboer, Stef J. F.

AU - Oud, Machteld M.

AU - van Beersum, Sylvia E. C.

AU - Schmidts, Miriam

AU - Beales, Philip L.

AU - Lu, Qianhao

AU - Giles, Rachel H.

AU - Szklarczyk, Radek

AU - Russell, Robert B.

AU - Gibson, Toby J.

AU - Johnson, Colin A.

AU - Blacque, Oliver E.

AU - Wolfrum, Uwe

AU - Boldt, Karsten

AU - Roepman, Ronald

AU - Hernandez-Hernandez, Victor

AU - Huynen, Martijn A.

N1 - Funding Information: 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]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We kindly acknowledge Prof. Dr. N. Katsanis and J. R. Willer from Duke University USA for providing several of the clone constructs used as baits in the SILAC and Y2H data sets. We also thank the Caenorhabditis elegans Genetics Center (Minnesota, USA), the National Bioresource project (Tokyo, Japan), the International C. elegans gene knockout consortium, and the C. elegans Million Mutation Project for nematode reagents. We thank Emine Bolat, Ideke Lamers, Mon-iek Riemersma, and Karlien Coene for performing yeast two-hybrid and SILAC experiments. Funding Information: InstitutesofHealthResearch[MOP-142243,MOP-82870andPJT-156042toMRL];MichaelSmith FoundationforHealthResearchtoMRLandVLJ; KidneyResearchScientistCoreEducationand NationalTrainingfellowshiptoVLJ;TheFoundation FightingBlindness[PPA-0717-0719-RADtoUW, RR,andMU];theDutchKidneyFoundation “KOUNCIL”consortium[CP11.18toRHG,PLBand RR];TheDeutscheForschungsgemeinschaft [ExcellencegrantCellNetworkstoRBRandQL, CRC1140“KidneyDisease–FromGenesto Mechanisms”toMS,collaborativeresearchcenter grantSFB-1411KIDGEMtoMS];Metakids FoundationtoRS;theNationalInstituteforHealth ResearchtoPLBandVH-H.PLBisanNIHRSenior Investigator;RadboudumcHypatiaTenureTrack Fellowship,RadboudUniversiteitexcellence fellowship,ERCstartinggrantTREATCilia,grant agreementno.716344toMS;andtheNetherlands OrganizationforScientificResearch[NWOVici-865.12.005toRR].Thefundershadnorolein studydesign,datacollectionandanalysis,decision topublish,orpreparationofthemanuscript. Publisher Copyright: © 2019 van Dam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2019/5/16

Y1 - 2019/5/16

N2 - 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/.

AB - 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/.

KW - DIFFERENTIATION

KW - EXPRESSION

KW - IDENTIFICATION

KW - INTRAFLAGELLAR TRANSPORT

KW - LEBER CONGENITAL AMAUROSIS

KW - MUTATIONS

KW - PRIMARY CILIUM

KW - RETINAL PHOTORECEPTOR CELLS

KW - SOLUTE-CARRIER-PROTEIN

KW - TRANSITION ZONE

U2 - 10.1371/journal.pone.0216705

DO - 10.1371/journal.pone.0216705

M3 - Article

C2 - 31095607

SN - 1932-6203

VL - 14

JO - PLOS ONE

JF - PLOS ONE

IS - 5

M1 - 0216705

ER -

CiliaCarta: An integrated and validated compendium of ciliary genes

Abstract

Keywords

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