58 results on '"Rob Jelier"'
Search Results
2. Wnt Signaling Induces Asymmetric Dynamics in the Actomyosin Cortex of the C. elegans Endomesodermal Precursor Cell
- Author
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Francesca Caroti, Wim Thiels, Michiel Vanslambrouck, and Rob Jelier
- Subjects
cell shape ,asymmetric division ,E-cadherin ,Wnt signaling ,Caenorhabditis elegans ,nonmuscle myosin ,Biology (General) ,QH301-705.5 - Abstract
During asymmetrical division of the endomesodermal precursor cell EMS, a cortical flow arises, and the daughter cells, endodermal precursor E and mesodermal precursor MS, have an enduring difference in the levels of F-actin and non-muscular myosin. Ablation of the cell cortex suggests that these observed differences lead to differences in cortical tension. The higher F-actin and myosin levels in the MS daughter coincide with cell shape changes and relatively lower tension, indicating a soft, actively moving cell, whereas the lower signal in the E daughter cell is associated with higher tension and a more rigid, spherical shape. The cortical flow is under control of the Wnt signaling pathway. Perturbing the pathway removes the asymmetry arising during EMS division and induces subtle defects in the cellular movements at the eight-cell stage. The perturbed cellular movement appears to be associated with an asymmetric distribution of E-cadherin across the EMS cytokinesis groove. ABpl forms a lamellipodium which preferentially adheres to MS by the E-cadherin HMR-1. The HMR-1 asymmetry across the groove is complete just at the moment cytokinesis completes. Perturbing Wnt signaling equalizes the HMR-1 distribution across the lamellipodium. We conclude that Wnt signaling induces a cortical flow during EMS division, which results in a transition in the cortical contractile network for the daughter cells, as well as an asymmetric distribution of E-cadherin.
- Published
- 2021
- Full Text
- View/download PDF
3. Physically asymmetric division of the C. elegans zygote ensures invariably successful embryogenesis
- Author
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Radek Jankele, Rob Jelier, and Pierre Gönczy
- Subjects
asymmetric cell division ,division timing ,embryogenesis ,lin-5 ,cell size ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Asymmetric divisions that yield daughter cells of different sizes are frequent during early embryogenesis, but the importance of such a physical difference for successful development remains poorly understood. Here, we investigated this question using the first division of Caenorhabditis elegans embryos, which yields a large AB cell and a small P1 cell. We equalized AB and P1 sizes using acute genetic inactivation or optogenetic manipulation of the spindle positioning protein LIN-5. We uncovered that only some embryos tolerated equalization, and that there was a size asymmetry threshold for viability. Cell lineage analysis of equalized embryos revealed an array of defects, including faster cell cycle progression in P1 descendants, as well as defects in cell positioning, division orientation, and cell fate. Moreover, equalized embryos were more susceptible to external compression. Overall, we conclude that unequal first cleavage is essential for invariably successful embryonic development of C. elegans.
- Published
- 2021
- Full Text
- View/download PDF
4. Network hubs affect evolvability.
- Author
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Jana Helsen, Jens Frickel, Rob Jelier, and Kevin J Verstrepen
- Subjects
Biology (General) ,QH301-705.5 - Abstract
The regulatory processes in cells are typically organized into complex genetic networks. However, it is still unclear how this network structure modulates the evolution of cellular regulation. One would expect that mutations in central and highly connected modules of a network (so-called hubs) would often result in a breakdown and therefore be an evolutionary dead end. However, a new study by Koubkova-Yu and colleagues finds that in some circumstances, altering a hub can offer a quick evolutionary advantage. Specifically, changes in a hub can induce significant phenotypic changes that allow organisms to move away from a local fitness peak, whereas the fitness defects caused by the perturbed hub can be mitigated by mutations in its interaction partners. Together, the results demonstrate how network architecture shapes and facilitates evolutionary adaptation.
- Published
- 2019
- Full Text
- View/download PDF
5. A Long Noncoding RNA on the Ribosome Is Required for Lifespan Extension
- Author
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Paul B. Essers, Julie Nonnekens, Yvonne J. Goos, Marco C. Betist, Marjon D. Viester, Britt Mossink, Nico Lansu, Hendrik C. Korswagen, Rob Jelier, Arjan B. Brenkman, and Alyson W. MacInnes
- Subjects
Biology (General) ,QH301-705.5 - Abstract
The biogenesis of ribosomes and their coordination of protein translation consume an enormous amount of cellular energy. As such, it has been established that the inhibition of either process can extend eukaryotic lifespan. Here, we used next-generation sequencing to compare ribosome-associated RNAs from normal strains of Caenorhabditis elegans to those carrying the life-extending daf-2 mutation. We found a long noncoding RNA (lncRNA), transcribed telomeric sequence 1 (tts-1), on ribosomes of the daf-2 mutant. Depleting tts-1 in daf-2 mutants increases ribosome levels and significantly shortens their extended lifespan. We find tts-1 is also required for the longer lifespan of the mitochondrial clk-1 mutants but not the feeding-defective eat-2 mutants. In line with this, the clk-1 mutants express more tts-1 and fewer ribosomes than the eat-2 mutants. Our results suggest that the expression of tts-1 functions in different longevity pathways to reduce ribosome levels in a way that promotes life extension.
- Published
- 2015
- Full Text
- View/download PDF
6. Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.
- Author
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Karin Voordeckers, Jacek Kominek, Anupam Das, Adriana Espinosa-Cantú, Dries De Maeyer, Ahmed Arslan, Michiel Van Pee, Elisa van der Zande, Wim Meert, Yudi Yang, Bo Zhu, Kathleen Marchal, Alexander DeLuna, Vera Van Noort, Rob Jelier, and Kevin J Verstrepen
- Subjects
Genetics ,QH426-470 - Abstract
Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.
- Published
- 2015
- Full Text
- View/download PDF
7. Integrated genome-scale prediction of detrimental mutations in transcription networks.
- Author
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Mirko Francesconi, Rob Jelier, and Ben Lehner
- Subjects
Genetics ,QH426-470 - Abstract
A central challenge in genetics is to understand when and why mutations alter the phenotype of an organism. The consequences of gene inhibition have been systematically studied and can be predicted reasonably well across a genome. However, many sequence variants important for disease and evolution may alter gene regulation rather than gene function. The consequences of altering a regulatory interaction (or "edge") rather than a gene (or "node") in a network have not been as extensively studied. Here we use an integrative analysis and evolutionary conservation to identify features that predict when the loss of a regulatory interaction is detrimental in the extensively mapped transcription network of budding yeast. Properties such as the strength of an interaction, location and context in a promoter, regulator and target gene importance, and the potential for compensation (redundancy) associate to some extent with interaction importance. Combined, however, these features predict quite well whether the loss of a regulatory interaction is detrimental across many promoters and for many different transcription factors. Thus, despite the potential for regulatory diversity, common principles can be used to understand and predict when changes in regulation are most harmful to an organism.
- Published
- 2011
- Full Text
- View/download PDF
8. spheresDT/Mpacts-PiCS: cell tracking and shape retrieval in membrane-labeled embryos.
- Author
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Wim Thiels, Bart Smeets, Maxim Cuvelier, Francesca Caroti, and Rob Jelier
- Published
- 2021
- Full Text
- View/download PDF
9. Stability of asymmetric cell division: A deformable cell model of cytokinesis applied to C. elegans
- Author
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Maxim Cuvelier, Jef Vangheel, Wim Thiels, Herman Ramon, Rob Jelier, and Bart Smeets
- Subjects
Biophysics - Abstract
Cell division during early embryogenesis is linked to key morphogenic events such as embryo symmetry breaking and tissue patterning. It is thought that the physical surrounding of cells together with cell intrinsic cues act as a mechanical "mold," guiding cell division to ensure these events are robust. To quantify how cell division is affected by the mechanical and geometrical environment, we present a novel computational mechanical model of cytokinesis, the final phase of cell division. Simulations with the model reproduced experimentally observed furrow dynamics and describe the volume ratio of daughter cells in asymmetric cell divisions, based on the position and orientation of the mitotic spindle. For dividing cells in geometrically confined environments, we show how the orientation of confinement relative to the division axis modulates the volume ratio in asymmetric cell division. Further, we quantified how cortex viscosity and surface tension determine the shape of a dividing cell and govern bubble-instabilities in asymmetric cell division. Finally, we simulated the formation of the three body axes via sequential (a)symmetric divisions up until the six-cell stage of early C. elegans development, which proceeds within the confines of an eggshell. We demonstrate how model input parameters spindle position and orientation provide sufficient information to reliably predict the volume ratio of daughter cells during the cleavage phase of development. However, for egg geometries perturbed by compression, the model predicts that a change in confinement alone is insufficient to explain experimentally observed differences in cell volume. This points to an effect of the compression on the spindle positioning mechanism. Additionally, the model predicts that confinement stabilizes asymmetric cell divisions against bubble-instabilities. ispartof: BIOPHYSICAL JOURNAL vol:122 issue:10 pages:1858-1867 ispartof: location:United States status: published
- Published
- 2023
10. Academia 2.0: removing the publisher middle-man while retaining impact.
- Author
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Raphael Poss, Sebastian Altmeyer, Mark Thompson, and Rob Jelier
- Published
- 2014
- Full Text
- View/download PDF
11. Cell shape characterization, alignment and comparison using FlowShape
- Author
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Rob Jelier, Wim Thiels, and Casper Van Bavel
- Abstract
MotivationThe shape of a cell reflects, among other things, actomyosin activity and adhesion properties. Cell shape is further tightly linked to cell differentiation and can reveal important cellular behaviors such as polarization. Hence, it is useful and informative to link cell shape to genetic and other perturbations. However, most currently used cell shape descriptors capture only simple geometric features such as volume and sphericity. We propose FlowShape, a new framework to study cell shapes in a complete and generic way.ResultsIn our framework a cell shape is first represented as a single function on a sphere. The curvature of the shape is measured and next mapped onto a sphere in a conformal manner. This special curvature map is then approximated by a series expansion: the spherical harmonics decomposition. This decomposition facilitates a wide range of shape analyses, including shape alignment, statistical cell shape comparison and inference of cell shape deformations over time. From this representation, we can reconstruct the cell shape using the Dirac equation. The new tool is applied to perform a complete, generic analysis of cell shapes, using the earlyCaenorhabditis elegansembryo as a model case. We distinguish and characterize the cells at the seven-cell stage. Next, a filter is designed to identify protrusions on the cell shape to highlight lamellipodia in cells. Furthermore, we use our framework to identify any shape changes following a gene knockdown of the Wnt pathway. Cells are first optimally aligned using the fast Fourier transform, followed by calculating an average shape. Shape differences between conditions are next quantified and compared to an empirical distribution. Finally, we put forward a highly performant implementation of the core algorithm, as well as routines to characterize, align and compare cell shapes, through the open-source software package FlowShape.AvailabilityThe data and code needed to recreate the results are freely available athttps://doi.org/10.5281/zenodo.7391185. The most recent version of the software is maintained athttps://bitbucket.org/pgmsembryogenesis/flowshape/.Author summaryWe present FlowShape, a framework for cell shape analysis, based on the concept ofspherical harmonicsdecomposition. This decomposition allows for any function defined on a sphere to be rewritten as a weighted sum of basis functions. Contrary to previous work, we use a single function to describe a shape, the mean curvature, which implies that the decomposition weights can be used as a complete shape description. The expression of a shape in this manner allows for very efficient calculations, as we illustrate with theC. elegansembryo as a model. The decomposition permits efficient comparison and alignment of shapes. We demonstrate this by clustering the cells in the early embryo and illustrating the different shapes by cluster. The decomposition further facilitates averaging of shapes and searching for particular features on the shape by defining filters that can then be efficiently applied. Finally, we illustrate how the framework can facilitate statistical comparisons between shapes.
- Published
- 2022
12. Yolk-deprivedCaenorhabditis eleganssecure brood size at the expense of competitive fitness
- Author
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Ellen Geens, Pieter Van de Walle, Francesca Caroti, Rob Jelier, Christian Steuwe, Liliane Schoofs, and Liesbet Temmerman
- Subjects
Phenotype ,Ecology ,Reproduction ,Health, Toxicology and Mutagenesis ,Animals ,Plant Science ,Caenorhabditis elegans ,Biochemistry, Genetics and Molecular Biology (miscellaneous) - Abstract
Oviparous animals support reproduction via the incorporation of yolk as a nutrient source into the eggs. In Caenorhabditis elegans, however, yolk proteins seem dispensable for fecundity, despite constituting the vast majority of the embryonic protein pool and acting as carriers for nutrient-rich lipids. Here, we used yolk protein-deprived C. elegans mutants to gain insight into the traits that may yet be influenced by yolk rationing. We show that massive yolk provisioning confers a temporal advantage during embryogenesis, while also increasing early juvenile body size and promoting competitive fitness. Opposite to species that reduce egg production under yolk deprivation, our results indicate that C. elegans relies on yolk as a fail-safe to secure offspring survival, rather than to maintain offspring numbers. electronic-issn: 2575-1077 linking-issn: 2575-1077 article-doi: 10.26508/lsa.202201675 article-pii: LSA-2022-01675 electronic-publication: 20230414 history: 2023/04/15 06:00 [medline] location-id: e202201675 nlm-unique-id: 101728869 owner: NLM publication-status: epublish revised: 20230417 source: Life Sci Alliance. 2023 Apr 14;6(6):e202201675. doi: 10.26508/lsa.202201675. Print 2023 Jun. status: In-Process subset: IM title-abbreviation: Life Sci Alliance ispartof: LIFE SCIENCE ALLIANCE vol:6 issue:6 ispartof: location:United States status: accepted
- Published
- 2023
13. Contextual Annotation of Web Pages for Interactive Browsing.
- Author
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Erik M. van Mulligen, Mario Diwersy, Bob J. A. Schijvenaars, Marc Weeber, C. Christiaan van der Eijk, Rob Jelier, Martijn J. Schuemie, Jan A. Kors, and Barend Mons
- Published
- 2004
- Full Text
- View/download PDF
14. Searching for geneRIFs: Concept-Based Query Expansion and Bayes Classification.
- Author
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Rob Jelier, Martijn J. Schuemie, C. Christiaan van der Eijk, Marc Weeber, Erik M. van Mulligen, Bob J. A. Schijvenaars, Barend Mons, and Jan A. Kors
- Published
- 2003
15. Stability of asymmetric cell division under confinement: A deformable cell model of cytokinesis applied to C. elegans development
- Author
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Maxim Cuvelier, Rob Jelier, Wim Thiels, and Bart Smeets
- Abstract
Cell division during early embryogenesis has been linked to key morphogenic events such as embryo symmetry breaking and tissue patterning. It is thought that boundary conditions together with cell intrinsic cues act as a mechanical “mold”, guiding cell division to ensure these events are more robust. We present a novel computational mechanical model of cytokinesis, the final phase of cell division, to investigate how cell division is affected by mechanical and geometrical boundary conditions. The model reproduces experimentally observed furrow dynamics and predicts the volume ratio of daughter cells in asymmetric cell divisions based on the position and orientation of the mitotic spindle. We show that the orientation of confinement relative to the division axis modulates the volume ratio in asymmetric cell division and quantified the mechanical contribution of cortex mechanics, relative to the mechanical properties of the furrow ring. We apply this model to early C. elegans development, which proceeds within the confines of an eggshell, and simulate the formation of the three body axes via sequential (a)symmetric divisions up until the six cell stage. We demonstrate that spindle position and orientation alone can be used to predict the volume ratio of daughter cells during the cleavage phase of development. However, for compression perturbed egg geometries, the model predicts that the change in confinement alone is insufficient to explain experimentally observed differences in cell volume, inferring an unmodeled underlying spindle positioning mechanism. Finally, the model predicts that confinement stabilizes asymmetric cell divisions against bubble-instabilities, which can arise due to elevated mitotic cortical tension.Author summaryA crucial morphogenic step during early embryonic development is symmetry breaking in the embryo. For C. elegans the formation of the three body axes can be traced back to the six cell stage, where tissue-topology is the result of symmetric and asymmetric divisions. How cell mechanical boundary conditions and cell intrinsic cues influence this process of symmetry breaking is still an open question, as currently, a quantitative mechanical description of cytokinesis in complex architectures is lacking. We developed a simple mechanical model of cell division, incorporated in an existing mechanical cortex model, to simulate cytokinesis in geometrically confined environments. Our approach was able to both capture furrow ring dynamics and predict the volume ratio of daughter cells accurately. By simulating early C. elegans development with different geometrical boundary conditions, we were able to trace back the origin of volume discrepancies between the experimental setups to a quantifiable shift in spindle positioning during cytokinesis. Finally, we showed how embryo confinement partially stabilizes bubble-instabilities that arise during asymmetric cell division during the early cleavage phase.
- Published
- 2022
16. Literature-aided interpretation of gene expression data with the weighted global test.
- Author
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Rob Jelier, Jelle J. Goeman, Kristina M. Hettne, Martijn J. Schuemie, Johan T. den Dunnen, and Peter A. C. 't Hoen
- Published
- 2011
- Full Text
- View/download PDF
17. Literature-based concept profiles for gene annotation: The issue of weighting.
- Author
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Rob Jelier, Martijn J. Schuemie, Peter-Jan Roes, Erik M. van Mulligen, and Jan A. Kors
- Published
- 2008
- Full Text
- View/download PDF
18. Co-occurrence based meta-analysis of scientific texts: retrieving biological relationships between genes.
- Author
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Rob Jelier, Guido Jenster, Lambert C. J. Dorssers, C. Christiaan van der Eijk, Erik M. van Mulligen, Barend Mons, and Jan A. Kors
- Published
- 2005
- Full Text
- View/download PDF
19. Wnt Signaling Induces Asymmetric Dynamics in the Actomyosin Cortex of the C. elegans Endomesodermal Precursor Cell
- Author
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Rob Jelier, Michiel Vanslambrouck, Wim Thiels, and Francesca Caroti
- Subjects
Cell division ,QH301-705.5 ,Chemistry ,Cadherin ,Wnt signaling pathway ,E-cadherin ,Cell Biology ,nonmuscle myosin ,asymmetric division ,Wnt signaling ,cell shape ,Cell biology ,Precursor cell ,Cell cortex ,Myosin ,Biology (General) ,Lamellipodium ,Caenorhabditis elegans ,Cytokinesis ,Developmental Biology - Abstract
During asymmetrical division of the endomesodermal precursor cell EMS, a cortical flow arises, and the daughter cells, endodermal precursor E and mesodermal precursor MS, have an enduring difference in the levels of F-actin and non-muscular myosin. Ablation of the cell cortex suggests that these observed differences lead to differences in cortical tension. The higher F-actin and myosin levels in the MS daughter coincide with cell shape changes and relatively lower tension, indicating a soft, actively moving cell, whereas the lower signal in the E daughter cell is associated with higher tension and a more rigid, spherical shape. The cortical flow is under control of the Wnt signaling pathway. Perturbing the pathway removes the asymmetry arising during EMS division and induces subtle defects in the cellular movements at the eight-cell stage. The perturbed cellular movement appears to be associated with an asymmetric distribution of E-cadherin across the EMS cytokinesis groove. ABpl forms a lamellipodium which preferentially adheres to MS by the E-cadherin HMR-1. The HMR-1 asymmetry across the groove is complete just at the moment cytokinesis completes. Perturbing Wnt signaling equalizes the HMR-1 distribution across the lamellipodium. We conclude that Wnt signaling induces a cortical flow during EMS division, which results in a transition in the cortical contractile network for the daughter cells, as well as an asymmetric distribution of E-cadherin. ispartof: Frontiers In Cell And Developmental Biology vol:9 ispartof: location:Switzerland status: published
- Published
- 2021
20. Distribution of information in biomedical abstracts and full-text publications.
- Author
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Martijn J. Schuemie, Marc Weeber, Bob J. A. Schijvenaars, Erik M. van Mulligen, C. Christiaan van der Eijk, Rob Jelier, Barend Mons, and Jan A. Kors
- Published
- 2004
- Full Text
- View/download PDF
21. Aca 2.0: Questions and Answers.
- Author
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Raphael Poss, Sebastian Altmeyer, Mark Thompson, and Rob Jelier
- Published
- 2014
22. TREC 2005 Genomics Track A Concept-Based Approach to Text Categorization.
- Author
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Bob J. A. Schijvenaars, Martijn J. Schuemie, Erik M. van Mulligen, Marc Weeber, Rob Jelier, Barend Mons, Jan A. Kors, and Wessel Kraaij
- Published
- 2005
23. Physically asymmetric division of theC. eleganszygote ensures invariably successful embryogenesis
- Author
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Rob Jelier, Pierre Gönczy, and Radek Jankele
- Subjects
0303 health sciences ,Zygote ,Cell division ,Cell ,Embryogenesis ,Embryo ,Biology ,Cell fate determination ,Division (mathematics) ,Cleavage (embryo) ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Asymmetric divisions that yield daughter cells of different sizes are frequent during early embryogenesis, but the importance of such a physical difference for successful development remains poorly understood. Here, we investigated this question using the first division ofC. elegansembryos, which yields a large AB cell and a small P1cell. We equalized AB and P1sizes using acute genetic inactivation or optogenetic manipulation of the spindle positioning protein LIN-5. We uncovered that only some embryos tolerated equalization, and that there was a size asymmetry threshold for viability. Cell lineage analysis of equalized embryos revealed an array of defects, including faster cell cycle progression in P1descendants, as well as defects in cell positioning, division orientation and cell fate. Moreover, equalized embryos were more susceptible to external compression. Overall, we conclude that unequal first cleavage is essential for invariably successful embryonic development ofC. elegans.
- Published
- 2021
24. MeSH Based Feedback, Concept Recognition and Stacked Classification for Curation Tasks.
- Author
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Wessel Kraaij, Stephan Raaijmakers, Marc Weeber, and Rob Jelier
- Published
- 2004
25. Ambiguity of Human Gene Symbols in LocusLink and MEDLINE: Creating an Inventory and a Disambiguation Test Collection.
- Author
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Marc Weeber, Bob J. A. Schijvenaars, Erik M. van Mulligen, Barend Mons, Rob Jelier, C. Christiaan van der Eijk, and Jan A. Kors
- Published
- 2003
26. Mining Microarray Datasets Aided by Knowledge Stored in Literature.
- Author
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Rob Jelier, Guido Jenster, Lambert C. J. Dorssers, Erik M. van Mulligen, Barend Mons, and Jan A. Kors
- Published
- 2003
27. Using Contextual Queries.
- Author
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Bob J. A. Schijvenaars, Erik M. van Mulligen, Mario Diwersy, Marc Weeber, C. Christiaan van der Eijk, Rob Jelier, Jan A. Kors, and Barend Mons
- Published
- 2003
28. Author response: Physically asymmetric division of the C. elegans zygote ensures invariably successful embryogenesis
- Author
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Pierre Gönczy, Rob Jelier, and Radek Jankele
- Subjects
Zygote ,Embryogenesis ,Biology ,Division (mathematics) ,Cell biology - Published
- 2020
29. Gene Loss Predictably Drives Evolutionary Adaptation
- Author
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Laura Vanderwaeren, Jana Helsen, Maria Tsontaki, Kevin J. Verstrepen, Rob Jelier, Karin Voordeckers, and Toon Santermans
- Subjects
fitness landscape ,Fitness landscape ,Mutant ,Adaptation, Biological ,adaptation ,Saccharomyces cerevisiae ,Biology ,AcademicSubjects/SCI01180 ,evolvability ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Gene Regulatory Networks ,experimental evolution ,Molecular Biology ,Gene ,Ecology, Evolution, Behavior and Systematics ,Discoveries ,030304 developmental biology ,0303 health sciences ,Experimental evolution ,AcademicSubjects/SCI01130 ,genetic network ,Phenotype ,Biological Evolution ,Evolvability ,Oxidative Stress ,Evolutionary biology ,Genetic Fitness ,Adaptation ,030217 neurology & neurosurgery ,Function (biology) ,Gene Deletion - Abstract
Loss of gene function is common throughout evolution, even though it often leads to reduced fitness. In this study, we systematically evaluated how an organism adapts after deleting genes that are important for growth under oxidative stress. By evolving, sequencing, and phenotyping over 200 yeast lineages, we found that gene loss can enhance an organism's capacity to evolve and adapt. Although gene loss often led to an immediate decrease in fitness, many mutants rapidly acquired suppressor mutations that restored fitness. Depending on the strain's genotype, some ultimately even attained higher fitness levels than similarly adapted wild-type cells. Further, cells with deletions in different modules of the genetic network followed distinct and predictable mutational trajectories. Finally, losing highly connected genes increased evolvability by facilitating the emergence of a more diverse array of phenotypes after adaptation. Together, our findings show that loss of specific parts of a genetic network can facilitate adaptation by opening alternative evolutionary paths. ispartof: MOLECULAR BIOLOGY AND EVOLUTION vol:37 issue:10 pages:2989-3002 ispartof: location:United States status: published
- Published
- 2020
30. Literature-aided meta-analysis of microarray data: a compendium study on muscle development and disease.
- Author
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Rob Jelier, Peter A. C. 't Hoen, Ellen Sterrenburg, Johan T. den Dunnen, Gert-Jan B. van Ommen, Jan A. Kors, and Barend Mons
- Published
- 2008
- Full Text
- View/download PDF
31. Text-derived concept profiles support assessment of DNA microarray data for acute myeloid leukemia and for androgen receptor stimulation.
- Author
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Rob Jelier, Guido Jenster, Lambert C. J. Dorssers, Bas J. Wouters, Peter J. M. Hendriksen, Barend Mons, Ruud Delwel, and Jan A. Kors
- Published
- 2007
- Full Text
- View/download PDF
32. Neuromedin U signaling regulates retrieval of learned salt avoidance in a C. elegans gustatory circuit
- Author
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Rob Jelier, Isabel Beets, Iene Rutten, Jan Watteyne, Liliane Schoofs, Sara Van Damme, Jeroen Lammertyn, Charline Borghgraef, Katleen Peymen, Elke Vandewyer, and Petrus Van der Auwera
- Subjects
0301 basic medicine ,Sensory Receptor Cells ,Science ,education ,Regulator ,General Physics and Astronomy ,Neuropeptide ,Sensory system ,Optogenetics ,Biology ,Sodium Chloride ,Models, Biological ,Neural circuits ,General Biochemistry, Genetics and Molecular Biology ,Article ,Learning and memory ,Animals, Genetically Modified ,03 medical and health sciences ,0302 clinical medicine ,Avoidance Learning ,Gene silencing ,Animals ,Amino Acid Sequence ,lcsh:Science ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Phylogeny ,Multidisciplinary ,Behavior, Animal ,Neuropeptides ,Chemotaxis ,General Chemistry ,030104 developmental biology ,Food ,Taste ,Mutation ,lcsh:Q ,Calcium ,Sensory processing ,Signal transduction ,Nerve Net ,Peptides ,Neuroscience ,030217 neurology & neurosurgery ,Neuromedin U ,Signal Transduction - Abstract
Learning and memory are regulated by neuromodulatory pathways, but the contribution and temporal requirement of most neuromodulators in a learning circuit are unknown. Here we identify the evolutionarily conserved neuromedin U (NMU) neuropeptide family as a regulator of C. elegans gustatory aversive learning. The NMU homolog CAPA-1 and its receptor NMUR-1 are required for the retrieval of learned salt avoidance. Gustatory aversive learning requires the release of CAPA-1 neuropeptides from sensory ASG neurons that respond to salt stimuli in an experience-dependent manner. Optogenetic silencing of CAPA-1 neurons blocks the expression, but not the acquisition, of learned salt avoidance. CAPA-1 signals through NMUR-1 in AFD sensory neurons to modulate two navigational strategies for salt chemotaxis. Aversive conditioning thus recruits NMU signaling to modulate locomotor programs for expressing learned avoidance behavior. Because NMU signaling is conserved across bilaterian animals, our findings incite further research into its function in other learning circuits., Learning and memory are regulated by neuropeptides. Here, the authors show that the neuropeptide CAPA-1 and its receptor NMUR-1 are required to retrieve learned salt avoidance in C. elegans. CAPA-1/NMUR-1 activation in AFD sensory neurons modulates locomotor programs to express learned avoidance.
- Published
- 2019
33. Network hubs affect evolvability
- Author
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Jens Frickel, Jana Helsen, Kevin J. Verstrepen, and Rob Jelier
- Subjects
0301 basic medicine ,Network architecture ,General Immunology and Microbiology ,QH301-705.5 ,Human evolutionary genetics ,General Neuroscience ,Cellular Regulation ,Gene regulatory network ,Network structure ,Biology ,Affect (psychology) ,General Biochemistry, Genetics and Molecular Biology ,Evolvability ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Dead end ,Evolutionary biology ,Biology (General) ,General Agricultural and Biological Sciences ,030217 neurology & neurosurgery - Abstract
The regulatory processes in cells are typically organized into complex genetic networks. However, it is still unclear how this network structure modulates the evolution of cellular regulation. One would expect that mutations in central and highly connected modules of a network (so-called hubs) would often result in a breakdown and therefore be an evolutionary dead end. However, a new study by Koubkova-Yu and colleagues finds that in some circumstances, altering a hub can offer a quick evolutionary advantage. Specifically, changes in a hub can induce significant phenotypic changes that allow organisms to move away from a local fitness peak, whereas the fitness defects caused by the perturbed hub can be mitigated by mutations in its interaction partners. Together, the results demonstrate how network architecture shapes and facilitates evolutionary adaptation. ispartof: PLOS BIOLOGY vol:17 issue:1 ispartof: location:United States status: published
- Published
- 2019
34. Mitochondrial ubiquinone-mediated longevity is marked by reduced cytoplasmic protein translation
- Author
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Riekelt H. Houtkooper, Toon Santermans, Alyson Winfield MacInnes, Rob Jelier, Marco Lezzerini, Marte Molenaars, and Georges E. Janssens
- Subjects
0303 health sciences ,Mutant ,Repressor ,Translation (biology) ,Biology ,Cell biology ,03 medical and health sciences ,Insulin receptor ,0302 clinical medicine ,Polysome ,biology.protein ,Gene silencing ,Gene ,Psychological repression ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Mutations in theclk-1gene impair mitochondrial ubiquinone biosynthesis and extend the lifespan ofC. elegans.We demonstrate here that this life extension is linked to the repression of cytoplasmic protein translation.Clk-1mutations inhibit polyribosome formation similarly todaf-2mutations that dampen insulin signaling. Comparisons of total versus polysomal RNAs inclk-1mutants reveal a reduction in the translational efficiencies of mRNAs coding for elements of the translation machinery and an increase in those coding for the oxidative phosphorylation and autophagy pathways. Knocking down the transcription initiation factor TAF-4, a protein that becomes sequestered in the cytoplasm during early embryogenesis to induce transcriptional silencing, ameliorates theclk-1inhibition of polyribosome formation. These results underscore a prominent role for the repression of cytoplasmic protein translation in eukaryotic lifespan extension, and suggest that mutations impairing mitochondrial function are able to exploit this repression similarly to reductions of insulin signaling. Moreover, this report reveals an unexpected role for TAF-4 as a repressor of polyribosome formation when ubiquinone biosynthesis is compromised.
- Published
- 2018
35. CoPub Mapper: mining MEDLINE based on search term co-publication.
- Author
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Blaise T. F. Alako, Antoine Veldhoven, Sjozef van Baal, Rob Jelier, Stefan Verhoeven, Ton Rullmann, Jan Polman, and Guido Jenster
- Published
- 2005
- Full Text
- View/download PDF
36. Comprehensive single cell-resolution analysis of the role of chromatin regulators in early C. elegans embryogenesis
- Author
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Erik Meijering, Oleh Dzyubachyk, Timo Zimmerman, Angela V. Krüger, Rob Jelier, Ben Lehner, and Radiology & Nuclear Medicine
- Subjects
Embryo, Nonmammalian ,Cell division ,ARID1A ,Embryonic Development ,Chromatin regulators ,Biology ,Chromatin remodeling ,Image analysis ,Mesoderm ,Single-cell analysis ,SDG 3 - Good Health and Well-being ,Chromosome Segregation ,Animals ,Humans ,RBBP4 ,Cell Lineage ,Epigenetics ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Molecular Biology ,Genes, Helminth ,Genetics ,Cell Nucleus ,Cell Cycle ,Endoderm ,Gene Expression Regulation, Developmental ,Cell Biology ,High dimensional phenotyping ,Chromatin ,Cell biology ,Embryogenesis ,C. elegans ,RNA Interference ,Gene expression ,Single-Cell Analysis ,Developmental Biology ,Bivalent chromatin - Abstract
Chromatin regulators are widely expressed proteins with diverse roles in gene expression, nuclear organization, cell cycle regulation, pluripotency, physiology and development, and are frequently mutated in human diseases such as cancer. Their inhibition often results in pleiotropic effects that are difficult to study using conventional approaches. We have developed a semi-automated nuclear tracking algorithm to quantify the divisions, movements and positions of all nuclei during the early development of Caenorhabditis elegans and have used it to systematically study the effects of inhibiting chromatin regulators. The resulting high dimensional datasets revealed that inhibition of multiple regulators, including F55A3.3 (encoding FACT subunit SUPT16H), lin-53 (RBBP4/7), rba-1 (RBBP4/7), set-16 (MLL2/3), hda-1 (HDAC1/2), swsn-7 (ARID2), and let-526 (ARID1A/1B) affected cell cycle progression and caused chromosome segregation defects. In contrast, inhibition of cir-1 (CIR1) accelerated cell division timing in specific cells of the AB lineage. The inhibition of RNA polymerase II also accelerated these division timings, suggesting that normal gene expression is required to delay cell cycle progression in multiple lineages in the early embryo. Quantitative analyses of the dataset suggested the existence of at least two functionally distinct SWI/SNF chromatin remodeling complex activities in the early embryo, and identified a redundant requirement for the egl-27 and lin-40 MTA orthologs in the development of endoderm and mesoderm lineages. Moreover, our dataset also revealed a characteristic rearrangement of chromatin to the nuclear periphery upon the inhibition of multiple general regulators of gene expression. Our systematic, comprehensive and quantitative datasets illustrate the power of single cell-resolution quantitative tracking and high dimensional phenotyping to investigate gene function. Furthermore, the results provide an overview of the functions of essential chromatin regulators during the early development of an animal. publisher: Elsevier articletitle: Comprehensive single cell-resolution analysis of the role of chromatin regulators in early C. elegans embryogenesis journaltitle: Developmental Biology articlelink: http://dx.doi.org/10.1016/j.ydbio.2014.10.014 content_type: article copyright: Copyright © 2014 Elsevier Inc. All rights reserved. ispartof: Developmental Biology vol:398 issue:2 pages:153-162 ispartof: location:United States status: published
- Published
- 2015
37. Predicting phenotypic variation in yeast from individual genome sequences
- Author
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Ben Lehner, Rob Jelier, Jennifer I. Semple, and Rosa Garcia-Verdugo
- Subjects
Saccharomyces cerevisiae Proteins ,Sequence analysis ,Sequence alignment ,Saccharomyces cerevisiae ,Biology ,Polymorphism, Single Nucleotide ,Genome ,Conserved sequence ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,INDEL Mutation ,Genetic variation ,Genetics ,Computer Simulation ,Gene ,Allele frequency ,Conserved Sequence ,030304 developmental biology ,0303 health sciences ,Models, Genetic ,Genetic Variation ,Sequence Analysis, DNA ,Phenotype ,ROC Curve ,Area Under Curve ,Genome, Fungal ,Sequence Alignment ,Algorithms ,030217 neurology & neurosurgery - Abstract
A central challenge in genetics is to predict phenotypic variation from individual genome sequences. Here we construct and evaluate phenotypic predictions for 19 strains of Saccharomyces cerevisiae. We use conservation-based methods to predict the impact of protein-coding variation within genes on protein function. We then rank strains using a prediction score that measures the total sum of function-altering changes in different sets of genes reported to influence over 100 phenotypes in genome-wide loss-of-function screens. We evaluate our predictions by comparing them with the observed growth rate and efficiency of 15 strains tested across 20 conditions in quantitative experiments. The median predictive performance, as measured by ROC AUC, was 0.76, and predictions were more accurate when the genes reported to influence a trait were highly connected in a functional gene network.
- Published
- 2011
38. Mitochondrial ubiquinone–mediated longevity is marked by reduced cytoplasmic mRNA translation
- Author
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Riekelt H. Houtkooper, Georges E. Janssens, Marte Molenaars, Rob Jelier, Alyson W. MacInnes, Marco Lezzerini, Toon Santermans, Graduate School, AGEM - Endocrinology, metabolism and nutrition, AGEM - Inborn errors of metabolism, Laboratory for General Clinical Chemistry, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases, APH - Aging & Later Life, and ARD - Amsterdam Reproduction and Development
- Subjects
Life Sciences & Biomedicine - Other Topics ,0301 basic medicine ,GENES ,Health, Toxicology and Mutagenesis ,EXTENDS LIFE-SPAN ,Repressor ,Plant Science ,Mitochondrion ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Article ,03 medical and health sciences ,0302 clinical medicine ,Polysome ,Gene silencing ,MUSCLE MASS ,DIETARY RESTRICTION ,Biology ,Gene ,Psychological repression ,Science & Technology ,Ecology ,biology ,Chemistry ,INHIBIT TRANSLATION ,Translation (biology) ,Cell biology ,Insulin receptor ,030104 developmental biology ,biology.protein ,GROWTH ,CLK-1 ,Life Sciences & Biomedicine ,EXTENSION ,BEHAVIOR ,030217 neurology & neurosurgery - Abstract
Mutations in theclk-1gene impair mitochondrial ubiquinone biosynthesis and extend the lifespan inCaenorhabditis elegans. We demonstrate here that this life extension is linked to the repression of cytoplasmic mRNA translation, independent of the alleged nuclear form of CLK-1.Clk-1mutations inhibit polyribosome formation similarly todaf-2mutations that dampen insulin signaling. Comparisons of total versus polysomal RNAs inclk-1(qm30)mutants reveal a reduction in the translational efficiencies of mRNAs coding for elements of the translation machinery and an increase in those coding for the oxidative phosphorylation and autophagy pathways. Knocking down the transcription initiation factor TATA-binding protein-associated factor 4, a protein that becomes sequestered in the cytoplasm during early embryogenesis to induce transcriptional silencing, ameliorates theclk-1inhibition of polyribosome formation. These results underscore a prominent role for the repression of cytoplasmic protein synthesis in eukaryotic lifespan extension and suggest that mutations impairing mitochondrial function are able to exploit this repression similarly to reductions of insulin signaling. Moreover, this report reveals an unexpected role for TATA-binding protein-associated factor 4 as a repressor of polyribosome formation when ubiquinone biosynthesis is compromised.
- Published
- 2018
39. Literature-based concept profiles for gene annotation: The issue of weighting
- Author
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Martijn J. Schuemie, Jan A. Kors, Peter-Jan Roes, Erik M. van Mulligen, Rob Jelier, and Medical Informatics
- Subjects
PubMed ,Computer science ,Abstracting and Indexing ,Information Theory ,Health Informatics ,Information theory ,computer.software_genre ,Pattern Recognition, Automated ,Set (abstract data type) ,Annotation ,Artificial Intelligence ,Terminology as Topic ,Databases, Genetic ,Protein Interaction Mapping ,Confidence Intervals ,Natural Language Processing ,Likelihood Functions ,Gene Expression Profiling ,Uncertainty ,Gene Annotation ,Weighting ,Uncertainty coefficient ,Genes ,ROC Curve ,Vocabulary, Controlled ,Likelihood-ratio test ,Vector space model ,Database Management Systems ,Data mining ,Neural Networks, Computer ,computer - Abstract
Background: Text-mining has been used to link biomedical concepts, such as genes or biological processes, to each other for annotation purposes or the generation of new hypotheses. To relate two concepts to each other several authors have used the vector space model, as vectors can be compared efficiently and transparently. Using this model, a concept is characterized by a list of associated concepts, together with weights that indicate the strength of the association. The associated concepts in the vectors and their weights are derived from a set of documents linked to the concept of interest. An important issue with this approach is the determination of the weights of the associated concepts. Various schemes have been proposed to determine these weights, but no comparative studies of the different approaches are available. Here we compare several weighting approaches in a large scale classification experiment. Methods: Three different techniques were evaluated: (1) weighting based on averaging, an empirical approach; (2) the log likelihood ratio, a test-based measure; (3) the uncertainty coefficient, an information-theory based measure. The weighting schemes were applied in a system that annotates genes with Gene Ontology codes. As the gold standard for our study we used the annotations provided by the Gene Ontology Annotation project. Classification performance was evaluated by means of the receiver operating characteristics (ROC) curve using the area under the curve (AUC) as the measure of performance. Results and discussion: All methods performed well with median AUC scores greater than 0.84, and scored considerably higher than a binary approach without any weighting. Especially for the more specific Gene Ontology codes excellent performance was observed. The differences between the methods were small when considering the whole experiment. However, the number of documents that were linked to a concept proved to be an important variable. When larger amounts of texts were available for the generation of the concepts' vectors, the performance of the methods diverged considerably, with the uncertainty coefficient then outperforming the two other methods. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2008
40. Co-occurrence based meta-analysis of scientific texts: retrieving biological relationships between genes
- Author
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Guido Jenster, Jan A. Kors, Lambert C. J. Dorssers, E.M. van Mulligen, Barend Mons, Rob Jelier, C. C. Van Der Eijk, Medical Informatics, Urology, and Pathology
- Subjects
Statistics and Probability ,PubMed ,Vocabulary ,Computer science ,media_common.quotation_subject ,Information Storage and Retrieval ,computer.software_genre ,Biochemistry ,Meta-Analysis as Topic ,Artificial Intelligence ,Protein Interaction Mapping ,Controlled vocabulary ,Representation (mathematics) ,Molecular Biology ,Natural Language Processing ,media_common ,Thesaurus (information retrieval) ,Information retrieval ,Proteins ,Computer Science Applications ,Hierarchical clustering ,Computational Mathematics ,Vocabulary, Controlled ,Computational Theory and Mathematics ,Test set ,Database Management Systems ,Data mining ,Periodicals as Topic ,computer - Abstract
Motivation: The advent of high-throughput experiments in molecular biology creates a need for methods to efficiently extract and use information for large numbers of genes. Recently, the associative concept space (ACS) has been developed for the representation of information extracted from biomedical literature. The ACS is a Euclidean space in which thesaurus concepts are positioned and the distances between concepts indicates their relatedness. The ACS uses co-occurrence of concepts as a source of information. In this paper we evaluate how well the system can retrieve functionally related genes and we compare its performance with a simple gene co-occurrence method. Results: To assess the performance of the ACS we composed a test set of five groups of functionally related genes. With the ACS good scores were obtained for four of the five groups. When compared to the gene co-occurrence method, the ACS is capable of revealing more functional biological relations and can achieve results with less literature available per gene. Hierarchical clustering was performed on the ACS output, as a potential aid to users, and was found to provide useful clusters. Our results suggest that the algorithm can be of value for researchers studying large numbers of genes. Availability: The ACS program is available upon request from the authors. Contact: r.jelier@erasmusmc.nl
- Published
- 2005
41. Distribution of information in biomedical abstracts and full-text publications
- Author
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Bob J. A. Schijvenaars, E.M. van Mulligen, Barend Mons, Martijn J. Schuemie, Marc Weeber, Jan A. Kors, Rob Jelier, C. C. Van Der Eijk, and Medical Informatics
- Subjects
Statistics and Probability ,Biomedical Research ,Computer science ,Abstracting and Indexing ,media_common.quotation_subject ,MEDLINE ,Section (typography) ,Distribution (economics) ,Information Storage and Retrieval ,Bibliometrics ,Biochemistry ,Set (abstract data type) ,Terminology as Topic ,Molecular Biology ,media_common ,Natural Language Processing ,Information retrieval ,business.industry ,Information Dissemination ,Biomedical information ,Ambiguity ,Computer Science Applications ,Computational Mathematics ,Gene nomenclature ,Computational Theory and Mathematics ,Genes ,Periodicals as Topic ,business - Abstract
Motivation: Full-text documents potentially hold more information than their abstracts, but require more resources for processing. We investigated the added value of full text over abstracts in terms of information content and occurrences of gene symbol—gene name combinations that can resolve gene-symbol ambiguity. Results: We analyzed a set of 3902 biomedical full-text articles. Different keyword measures indicate that information density is highest in abstracts, but that the information coverage in full texts is much greater than in abstracts. Analysis of five different standard sections of articles shows that the highest information coverage is located in the results section. Still, 30–40% of the information mentioned in each section is unique to that section. Only 30% of the gene symbols in the abstract are accompanied by their corresponding names, and a further 8% of the gene names are found in the full text. In the full text, only 18% of the gene symbols are accompanied by their gene names.
- Published
- 2004
42. WormJam: A consensusC. elegansMetabolic Reconstruction and Metabolomics Community and Workshop Series
- Author
-
Michael Witting, Sven Bergmann, Artur B. Lourenço, Filipe Cabreiro, Chintan Joshi, Christoph Kaleta, Toon Santermans, Paul R. Ebert, Varun B. Kothamachu, Manusnan Suriyalaksh, Paul D. Dobson, Juliette Pearce, Jake P. N. Hattwell, Pasquale Scarcia, Yu Nie, Aleksandra Zečić, Benjamin D. Towbin, Johannes Zimmermann, Nicolas Le Novère, Marta Artal-Sanz, Rob Jelier, Nicolas Rodriguez, Mary Ann Tuli, Reuben L. Smith, Horst Joachim Schirra, Hooman Hefzi, Ming Sheng, Abraham Mains, Jake G. Bundy, David Weinkove, Michel van Weeghel, Riekelt H. Houtkooper, Povilas Norvaisas, Olivia Casanueva, Nathan E. Lewis, Bart P. Braeckman, Cristian Riccio, and Janna Hastings
- Subjects
0301 basic medicine ,biology ,Global challenges ,Meeting Report ,biology.organism_classification ,Data science ,Flux balance analysis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Metabolomics ,570 Life sciences ,Cost action ,030217 neurology & neurosurgery ,Caenorhabditis elegans - Abstract
A GENiE (EU COST action, www.worm-genie.eu) workshop was held at the Babraham Institute in Cambridge, UK on April 19 and 20, 2017, to discuss global challenges around Caenorhabditis elegans metabol...
- Published
- 2017
43. Adaptation to High Ethanol Reveals Complex Evolutionary Pathways
- Author
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Yudi Yang, Vera van Noort, Kathleen Marchal, Dries De Maeyer, Ahmed Arslan, Rob Jelier, Kevin J. Verstrepen, Michiel Van Pee, Anupam J. Das, Alexander DeLuna, Bo Zhu, Elisa van der Zande, Wim Meert, Jacek Kominek, Karin Voordeckers, Adriana Espinosa-Cantú, and Zhang, Jianzhi
- Subjects
Cancer Research ,BUDDING YEAST ,GENE DISRUPTION ,lcsh:QH426-470 ,DNA repair ,Haploidy ,YEAST SACCHAROMYCES-CEREVISIAE ,Quantitative trait locus ,Biology ,medicine.disease_cause ,CLONAL INTERFERENCE ,03 medical and health sciences ,0302 clinical medicine ,GENOME-WIDE IDENTIFICATION ,HIGH MUTATION-RATES ,Genetics ,medicine ,Copy-number variation ,Molecular Biology ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Mutation ,Experimental evolution ,Ethanol ,TOLERANT MUTANTS ,Clonal interference ,Biology and Life Sciences ,Aneuploidy ,Adaptation, Physiological ,Phenotype ,ADAPTIVE EVOLUTION ,lcsh:Genetics ,ESCHERICHIA-COLI ,E. COLI ,Adaptation ,030217 neurology & neurosurgery ,Research Article - Abstract
Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts., Author Summary Organisms can evolve resistance to specific stress factors, which allows them to thrive in environments where non-adapted organisms fail to grow. However, the molecular mechanisms that underlie adaptation to complex stress factors that interfere with basic cellular processes are poorly understood. In this study, we reveal how yeast populations adapt to high ethanol concentrations, an ecologically and industrially relevant stress that is still poorly understood. We exposed six independent populations of genetically identical yeast cells to gradually increasing ethanol levels, and we monitored the changes in their DNA sequence over a two-year period. Together with novel computational analyses, we could identify the mutational dynamics and molecular mechanisms underlying increased ethanol resistance. Our results show how adaptation to high ethanol is complex and can be reached through different mutational pathways. Together, our study offers a detailed picture of how populations adapt to a complex continuous stress and identifies several mutations that increase ethanol resistance, which opens new routes to obtain superior biofuel yeast strains.
- Published
- 2015
44. Model-based approach for tracking embryogenesis in Caenorhabditis elegans fluorescence microscopy data
- Author
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Oleh Dzyubachyk, Wiro J. Niessen, Rob Jelier, Erik Meijering, Ben Lehner, Medical Informatics, and Radiology & Nuclear Medicine
- Subjects
ved/biology.organism_classification_rank.species ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Embryonic Development ,Models, Biological ,03 medical and health sciences ,0302 clinical medicine ,Cut ,Animals ,Segmentation ,Computer vision ,Caenorhabditis elegans ,Model organism ,Cluster analysis ,030304 developmental biology ,0303 health sciences ,biology ,ved/biology ,business.industry ,Pattern recognition ,Image segmentation ,biology.organism_classification ,Tree (data structure) ,Microscopy, Fluorescence ,Artificial intelligence ,business ,Algorithms ,030217 neurology & neurosurgery ,Test data - Abstract
The nematode Caenorhabditis elegans (C. elegans) is a widely used model organism in biological investigations. Due to its well-known and invariant cell lineage tree, it can be used to study the effects of mutations and various disease processes. Effective and efficient analysis of the wealth of time-lapse fluorescence microscopy image data acquired in such studies requires automation of the cell segmentation and tracking tasks involved. This is hampered by many factors, including autofluorescence effects, low and uneven contrast throughout the images, high noise levels, large numbers of possibly simultaneous cell divisions, and touching or clustering cells. In this paper, we present a new algorithm for segmentation and tracking of cells in C. elegans embryogenesis image data. It is based on the model evolution framework for image segmentation and uses a novel multi-object tracking scheme based on energy minimization via graph cuts. Preliminary experiments on publicly available test data demonstrate the potential of the algorithm compared to existing approaches.
- Published
- 2009
45. Anni 2.0: a multipurpose text-mining tool for the life sciences
- Author
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Jan A. Kors, Guido Jenster, Lambert C. J. Dorssers, Rob Jelier, Antoine Veldhoven, Martijn J. Schuemie, Medical Informatics, Pathology, and Urology
- Subjects
Abstracting and Indexing ,Interface (Java) ,MEDLINE ,InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL ,Information Storage and Retrieval ,PROTEIN ,Information needs ,Computational biology ,Ontology (information science) ,Biology ,GENERATING HYPOTHESES ,CONCEPT PROFILES ,KNOWLEDGE DISCOVERY ,World Wide Web ,Knowledge extraction ,ANAPHASE-PROMOTING COMPLEX ,Use case ,FISH-OIL ,Genetics & Heredity ,Science & Technology ,IDENTIFICATION ,business.industry ,GENE ONTOLOGY ,Usability ,PROSTATE-CANCER ,Differentially expressed genes ,ComputingMethodologies_PATTERNRECOGNITION ,Biotechnology & Applied Microbiology ,business ,Life Sciences & Biomedicine ,Software ,CHRONIC HEPATITIS-C - Abstract
Anni 2.0 provides an ontology-based interface to MEDLINE., Anni 2.0 is an online tool () to aid the biomedical researcher with a broad range of information needs. Anni provides an ontology-based interface to MEDLINE and retrieves documents and associations for several classes of biomedical concepts, including genes, drugs and diseases, with established text-mining technology. In this article we illustrate Anni's usability by applying the tool to two use cases: interpretation of a set of differentially expressed genes, and literature-based knowledge discovery.
- Published
- 2008
46. A Long Noncoding RNA on the Ribosome Is Required for Lifespan Extension
- Author
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Rob Jelier, Alyson W. MacInnes, Marjon D. Viester, Paul B. Essers, Hendrik C. Korswagen, Yvonne J. Goos, Nico Lansu, Arjan B. Brenkman, Marco C. Betist, Julie Nonnekens, Britt Mossink, and Hubrecht Institute for Developmental Biology and Stem Cell Research
- Subjects
Mutant ,DAF-16 ,PROTEIN ,Biology ,METABOLISM ,medicine.disease_cause ,Ribosome ,General Biochemistry, Genetics and Molecular Biology ,Gene expression ,TRANSCRIPTS ,medicine ,Daf-16 ,LONGEVITY ,lcsh:QH301-705.5 ,Caenorhabditis elegans ,GENE-EXPRESSION ,Genetics ,Mutation ,Translation (biology) ,biology.organism_classification ,Long non-coding RNA ,lcsh:Biology (General) ,C-ELEGANS ,TRANSLATION ,CAENORHABDITIS-ELEGANS ,RESTRICTION - Abstract
The biogenesis of ribosomes and their coordination of protein translation consume an enormous amount of cellular energy. As such, it has been established that the inhibition of either process can extend eukaryotic lifespan. Here, we used next-generation sequencing to compare ribosome-associated RNAs from normal strains of Caenorhabditis elegans to those carrying the life-extending daf-2 mutation. We found a long noncoding RNA (lncRNA), transcribed telomeric sequence 1 (tts-1), on ribosomes of the daf-2 mutant. Depleting tts-1 in daf-2 mutants increases ribosome levels and significantly shortens their extended lifespan. We find tts-1 is also required for the longer lifespan of the mitochondrial clk-1 mutants but not the feeding-defective eat-2 mutants. In line with this, the clk-1 mutants express more tts-1 and fewer ribosomes than the eat-2 mutants. Our results suggest that the expression of tts-1 functions in different longevity pathways to reduce ribosome levels in a way that promotes life extension. publisher: Elsevier articletitle: A Long Noncoding RNA on the Ribosome Is Required for Lifespan Extension journaltitle: Cell Reports articlelink: http://dx.doi.org/10.1016/j.celrep.2014.12.029 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. ispartof: Cell Reports vol:10 issue:3 pages:339-345 ispartof: location:United States status: published
- Published
- 2015
47. Mining microarray datasets aided by knowledge stored in literature
- Author
-
Rob, Jelier, Guido, Jenster, Lambert C, Dorssers, Erik M, Van Mulligen, Barend, Mons, and Jan A, Kors
- Subjects
ComputingMethodologies_PATTERNRECOGNITION ,Genes ,Vocabulary, Controlled ,Databases, Genetic ,Humans ,Information Storage and Retrieval ,Article ,Oligonucleotide Array Sequence Analysis - Abstract
DNA microarray technology produces large amounts of data. For data mining of these datasets, background information on genes can be helpful. Unfortunately most information is stored in free text. Here, we present an approach to use this information for DNA microarray data mining.
- Published
- 2004
48. Literature-aided meta-analysis of microarray data: a compendium study on muscle development and disease
- Author
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Ellen Sterrenburg, Rob Jelier, Barend Mons, Gert-Jan B. van Ommen, Johan T. den Dunnen, Peter A C 't Hoen, Jan A. Kors, and Medical Informatics
- Subjects
Microarray ,MEDLINE ,Computational biology ,Biology ,lcsh:Computer applications to medicine. Medical informatics ,Muscle Development ,Biochemistry ,Pattern Recognition, Automated ,Transcriptome ,Meta-Analysis as Topic ,Muscular Diseases ,Structural Biology ,Artificial Intelligence ,Animals ,Cluster Analysis ,Humans ,lcsh:QH301-705.5 ,Molecular Biology ,Genetic association ,Natural Language Processing ,Oligonucleotide Array Sequence Analysis ,Genetics ,Microarray analysis techniques ,Applied Mathematics ,Methodology Article ,Gene Expression Profiling ,Publications ,Reproducibility of Results ,Gene Annotation ,Computer Science Applications ,Gene expression profiling ,lcsh:Biology (General) ,Vocabulary, Controlled ,Meta-analysis ,Models, Animal ,lcsh:R858-859.7 ,DNA microarray - Abstract
Background Comparative analysis of expression microarray studies is difficult due to the large influence of technical factors on experimental outcome. Still, the identified differentially expressed genes may hint at the same biological processes. However, manually curated assignment of genes to biological processes, such as pursued by the Gene Ontology (GO) consortium, is incomplete and limited. We hypothesised that automatic association of genes with biological processes through thesaurus-controlled mining of Medline abstracts would be more effective. Therefore, we developed a novel algorithm (LAMA: Literature-Aided Meta-Analysis) to quantify the similarity between transcriptomics studies. We evaluated our algorithm on a large compendium of 102 microarray studies published in the field of muscle development and disease, and compared it to similarity measures based on gene overlap and over-representation of biological processes assigned by GO. Results While the overlap in both genes and overrepresented GO-terms was poor, LAMA retrieved many more biologically meaningful links between studies, with substantially lower influence of technical factors. LAMA correctly grouped muscular dystrophy, regeneration and myositis studies, and linked patient and corresponding mouse model studies. LAMA also retrieves the connecting biological concepts. Among other new discoveries, we associated cullin proteins, a class of ubiquitinylation proteins, with genes down-regulated during muscle regeneration, whereas ubiquitinylation was previously reported to be activated during the inverse process: muscle atrophy. Conclusion Our literature-based association analysis is capable of finding hidden common biological denominators in microarray studies, and circumvents the need for raw data analysis or curated gene annotation databases.
- Published
- 2008
49. Text-derived concept profiles support assessment of DNA microarray data for acute myeloid leukemia and for androgen receptor stimulation
- Author
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P. J. M. Hendriksen, Bas J. Wouters, Ruud Delwel, Jan A. Kors, Lambert C. J. Dorssers, Rob Jelier, Guido Jenster, Barend Mons, Gezondheidsrisico Analyse en Toxicologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: NUTRIM - R4 - Gene-environment interaction, Medical Informatics, Urology, Pathology, and Hematology
- Subjects
Male ,Information Storage and Retrieval ,Biochemistry ,Structural Biology ,Dna microarray data ,Databases, Genetic ,Diagnosis, Computer-Assisted ,MELANOSOMES ,lcsh:QH301-705.5 ,Oligonucleotide Array Sequence Analysis ,GENE-EXPRESSION ,Genetics ,Applied Mathematics ,Myeloid leukemia ,ASSOCIATION ,Computer Science Applications ,Neoplasm Proteins ,Receptors, Androgen ,Leukemia, Monocytic, Acute ,lcsh:R858-859.7 ,DNA microarray ,Life Sciences & Biomedicine ,Algorithms ,Research Article ,Biochemistry & Molecular Biology ,MEDLINE ,ANTIGEN ,EFFECTOR ,Context (language use) ,Biology ,lcsh:Computer applications to medicine. Medical informatics ,Sensitivity and Specificity ,Biochemical Research Methods ,Text mining ,Biomarkers, Tumor ,Humans ,Molecular Biology ,Gene ,Natural Language Processing ,Science & Technology ,business.industry ,Gene Expression Profiling ,Prostatic Neoplasms ,Reproducibility of Results ,Gene expression profiling ,Androgen receptor ,Biotechnology & Applied Microbiology ,lcsh:Biology (General) ,CELLS ,Mathematical & Computational Biology ,business - Abstract
Background High-throughput experiments, such as with DNA microarrays, typically result in hundreds of genes potentially relevant to the process under study, rendering the interpretation of these experiments problematic. Here, we propose and evaluate an approach to find functional associations between large numbers of genes and other biomedical concepts from free-text literature. For each gene, a profile of related concepts is constructed that summarizes the context in which the gene is mentioned in literature. We assign a weight to each concept in the profile based on a likelihood ratio measure. Gene concept profiles can then be clustered to find related genes and other concepts. Results The experimental validation was done in two steps. We first applied our method on a controlled test set. After this proved to be successful the datasets from two DNA microarray experiments were analyzed in the same way and the results were evaluated by domain experts. The first dataset was a gene-expression profile that characterizes the cancer cells of a group of acute myeloid leukemia patients. For this group of patients the biological background of the cancer cells is largely unknown. Using our methodology we found an association of these cells to monocytes, which agreed with other experimental evidence. The second data set consisted of differentially expressed genes following androgen receptor stimulation in a prostate cancer cell line. Based on the analysis we put forward a hypothesis about the biological processes induced in these studied cells: secretory lysosomes are involved in the production of prostatic fluid and their development and/or secretion are androgen-regulated processes. Conclusion Our method can be used to analyze DNA microarray datasets based on information explicitly and implicitly available in the literature. We provide a publicly available tool, dubbed Anni, for this purpose.
- Published
- 2007
50. [Untitled]
- Author
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Jan Polman, Rob Jelier, Antoine Veldhoven, Stefan Verhoeven, Guido Jenster, Sjozef van Baal, Ton Rullmann, and Blaise T. F. Alako
- Subjects
Expressed sequence tag ,Microarray ,Microarray analysis techniques ,Computer science ,Applied Mathematics ,Sequence alignment ,Computational biology ,Biological process ,computer.software_genre ,Biochemistry ,Computer Science Applications ,Gene expression profiling ,Gene nomenclature ,Structural Biology ,Gene expression ,DNA microarray experiment ,Data mining ,DNA microarray ,Cluster analysis ,human activities ,Molecular Biology ,Gene ,computer - Abstract
High throughput microarray analyses result in many differentially expressed genes that are potentially responsible for the biological process of interest. In order to identify biological similarities between genes, publications from MEDLINE were identified in which pairs of gene names and combinations of gene name with specific keywords were co-mentioned. MEDLINE search strings for 15,621 known genes and 3,731 keywords were generated and validated. PubMed IDs were retrieved from MEDLINE and relative probability of co-occurrences of all gene-gene and gene-keyword pairs determined. To assess gene clustering according to literature co-publication, 150 genes consisting of 8 sets with known connections (same pathway, same protein complex, or same cellular localization, etc.) were run through the program. Receiver operator characteristics (ROC) analyses showed that most gene sets were clustered much better than expected by random chance. To test grouping of genes from real microarray data, 221 differentially expressed genes from a microarray experiment were analyzed with CoPub Mapper, which resulted in several relevant clusters of genes with biological process and disease keywords. In addition, all genes versus keywords were hierarchical clustered to reveal a complete grouping of published genes based on co-occurrence. The CoPub Mapper program allows for quick and versatile querying of co-published genes and keywords and can be successfully used to cluster predefined groups of genes and microarray data.
- Published
- 2005
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