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Your search keyword '"van Dam, Teunis J. P."' showing total 4 results
Start Over Author "van Dam, Teunis J. P." Topic genetics
4 results on '"van Dam, Teunis J. P."'

1. Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts

Author

van der Lee, Robin, Wiel, Laurens, van Dam, Teunis J P, Huynen, Martijn A, Sub Bioinformatics, Theoretical Biology and Bioinformatics, Sub Bioinformatics, and Theoretical Biology and Bioinformatics

Subjects
0301 basic medicine, Primates, Genome evolution, Evolution, Gene Conversion, Genomics, Computational biology, Major histocompatibility complex, Genome, Evolution, Molecular, 03 medical and health sciences, Viral Proteins, Genetic, Receptors, Genetics, Journal Article, Animals, Humans, Selection, Genetic, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Gene, Selection, Selection (genetic algorithm), biology, Immunity, Molecular, Genetic Variation, Proteins, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Acquired immune system, Phenotype, Virus, 030104 developmental biology, Virus Diseases, Multigene Family, Host-Pathogen Interactions, biology.protein, Receptors, Virus, Artifacts, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
Abstract

Hotspots of rapid genome evolution hold clues about human adaptation. We present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection in 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our new procedure is stringent and reveals substantial artefacts (20% of initial predictions) that have inflated previous estimates. The final 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immunity, secreted and cell membrane proteins (e.g. pattern recognition, complement, cytokines, immune receptors, MHC, Siglecs). We also find evidence for positive selection in reproduction and chromosome segregation (e.g. centromere-associated CENPO, CENPT), apolipoproteins, smell/taste receptors and mitochondrial proteins. Focusing on the virus–host interaction, we retrieve most evolutionary conflicts known to influence antiviral activity (e.g. TRIM5, MAVS, SAMHD1, tetherin) and predict 70 novel cases through integration with virus–human interaction data. Protein structure analysis further identifies positive selection in the interaction interfaces between viruses and their cellular receptors (CD4-HIV; CD46-measles, adenoviruses; CD55-picornaviruses). Finally, primate PSG consistently show high sequence variation in human exomes, suggesting ongoing evolution. Our curated dataset of positive selection is a rich source for studying the genetics underlying human (antiviral) phenotypes. Procedures and data are available at https://github.com/robinvanderlee/positive-selection.

Published
2017

2. Measuring the impact of gene prediction on gene loss estimates in Eukaryotes by quantifying falsely inferred absences.

Author

Deutekom, Eva S., Vosseberg, Julian, van Dam, Teunis J. P., and Snel, Berend

Subjects
GENES, STRAIN hardening, MOLECULAR evolution, EUKARYOTES, COMPUTATIONAL biology, ESTIMATES
Abstract

In recent years it became clear that in eukaryotic genome evolution gene loss is prevalent over gene gain. However, the absence of genes in an annotated genome is not always equivalent to the loss of genes. Due to sequencing issues, or incorrect gene prediction, genes can be falsely inferred as absent. This implies that loss estimates are overestimated and, more generally, that falsely inferred absences impact genomic comparative studies. However, reliable estimates of how prevalent this issue is are lacking. Here we quantified the impact of gene prediction on gene loss estimates in eukaryotes by analysing 209 phylogenetically diverse eukaryotic organisms and comparing their predicted proteomes to that of their respective six-frame translated genomes. We observe that 4.61% of domains per species were falsely inferred to be absent for Pfam domains predicted to have been present in the last eukaryotic common ancestor. Between phylogenetically different categories this estimate varies substantially: for clade-specific loss (ancestral loss) we found 1.30% and for species-specific loss 16.88% to be falsely inferred as absent. For BUSCO 1-to-1 orthologous families, 18.30% were falsely inferred to be absent. Finally, we showed that falsely inferred absences indeed impact loss estimates, with the number of losses decreasing by 11.78%. Our work strengthens the increasing number of studies showing that gene loss is an important factor in eukaryotic genome evolution. However, while we demonstrate that on average inferring gene absences from predicted proteomes is reliable, caution is warranted when inferring species-specific absences. [ABSTRACT FROM AUTHOR]

Published
2019
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3. CiliaCarta: An integrated and validated compendium of ciliary genes.

Author

van Dam, Teunis J. P., Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard W., Lambacher, Nils J., Li, Chunmei, Jensen, Victor L., Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., and Franco, Brunella

Subjects
*CILIA & ciliary motion, *DEVELOPMENTAL biology, *CYTOLOGY, *GENES, *LIFE sciences, *OUTLINES
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 . [ABSTRACT FROM AUTHOR]

Published
2019
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4. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

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, Erik de Vrieze, Grischa Toedt, 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, Sub Bioinformatics, Theoretical Biology and Bioinformatics, MUMC+: DA KG Lab Centraal Lab (9), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, van Dam, Teunis J P, Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A, Rix, Suzanne, Dougherty, Gerard W, Lambacher, Nils J, Li, Chunmei, Jensen, Victor L, Leroux, Michel R, Hjeij, Rim, Horn, Nicola, Texier, Yve, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F, Franco, Brunella, Mans, Dorus A, van Wijk, Erwin, Képès, Françoi, Slaats, Gisela G, Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantino, Ueffing, Mariu, Nguyen, Thanh-Minh T, Letteboer, Stef J F, Oud, Machteld M, van Beersum, Sylvia E C, Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H, Szklarczyk, Radek, Russell, Robert B, Gibson, Toby J, Johnson, Colin A, Blacque, Oliver E, Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn A

Subjects
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, 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, Multidisciplinary, Spectrometric Identification of Proteins, Proteomic Databases, Nucleotides, Cilium, Stable Isotope Labeling by Amino Acids in Cell Culture, photoreceptors, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Animal Models, Phenotype, INTRAFLAGELLAR TRANSPORT, DIFFERENTIATION, 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
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/. 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].

Published
2019

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