References of "Trefois, Christophe 50003220"
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See detailFractalis: A scalable open-source service for platform-independent interactive visual analysis of biomedical data
Herzinger, Sascha UL; Groues, Valentin UL; Gu, Wei UL et al

in GigaScience (2018)

Background: Translational research platforms share the aim to promote a deeper understanding of stored data by providing visualization and analysis tools for data exploration and hypothesis generation ... [more ▼]

Background: Translational research platforms share the aim to promote a deeper understanding of stored data by providing visualization and analysis tools for data exploration and hypothesis generation. However, such tools are usually platform-bound and are not easily reusable by other systems. Furthermore, they rarely address access restriction issues when direct data transfer is not permitted. In this article we present an analytical service that works in tandem with a visualization library to address these problems. Findings: Using a combination of existing technologies and a platform-specific data abstraction layer we developed a service that is capable of providing existing web-based data warehouses and repositories with platform-independent visual analytical capabilities. The design of this service also allows for federated data analysis by eliminating the need to move the data directly to the researcher. Instead, all operations are based on statistics and interactive charts without direct access to the dataset. Conclusion: The software presented in this article has a potential to help translational researchers achieve a better understanding of a given dataset and quickly generate new hypothesis. Furthermore, it provides a framework that can be used to share and reuse explorative analysis tools within the community. [less ▲]

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See detailCharacterization of Differentiated SH-SY5Y as Neuronal Screening Model Reveals Increased Oxidative Vulnerability
Antony, Paul UL; Forster, Julia UL; Köglsberger, Sandra UL et al

in Journal of Biomolecular Screening : The Official Journal of the Society for Biomolecular Screening (2016)

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See detailCritical transitions in chronic disease: transferring concepts from ecology to systems medicine
Trefois, Christophe UL; Antony, Paul UL; Goncalves, Jorge UL et al

in Current Opinion in Biotechnology (2015), 34

Ecosystems and biological systems are known to be inherently complex and to exhibit nonlinear dynamics. Diseases such as microbiome dysregulation or depression can be seen as complex systems as well and ... [more ▼]

Ecosystems and biological systems are known to be inherently complex and to exhibit nonlinear dynamics. Diseases such as microbiome dysregulation or depression can be seen as complex systems as well and were shown to exhibit patterns of nonlinearity in their response to perturbations. These nonlinearities can be revealed by a sudden shift in system states, for instance from health to disease. The identification and characterization of early warning signals which could predict upcoming critical transitions is of primordial interest as prevention of disease onset is a major aim in health care. In this review, we focus on recent evidence for critical transitions in diseases and discuss the potential of such studies for therapeutic applications. [less ▲]

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See detailEvaluation of Cell Line Suitability for Disease Specific Perturbation Experiments.
Biryukov, Maria UL; Antony, Paul UL; Krishna, Abhimanyu UL et al

in Lausen, Berthold; Krolak-Schwerdt, Sabine; Böhmer, Matthias (Eds.) Data Science, Learning by Latent Structures, and Knowledge Discovery (2015, February 20)

Cell lines are widely used in translational biomedical research to study the genetic basis of diseases. A major approach for experimental disease modeling are genetic perturbation experiments that aim to ... [more ▼]

Cell lines are widely used in translational biomedical research to study the genetic basis of diseases. A major approach for experimental disease modeling are genetic perturbation experiments that aim to trigger selected cellular disease states. In this type of experiments it is crucial to ensure that the targeted disease- related genes and pathways are intact in the used cell line. In this work we are developing a framework which integrates genetic sequence information and disease- specific network analysis for evaluating disease-specific cell line suitability. [less ▲]

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See detailPlatelet mitochondrial membrane potential in Parkinson's disease.
Antony, Paul UL; Boyd, Olga UL; Trefois, Christophe UL et al

in Annals of clinical and translational neurology (2015), 2(1), 67-73

OBJECTIVE: Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease (IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial ... [more ▼]

OBJECTIVE: Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease (IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial function at the level of selected enzymatic activities in peripheral tissues have produced conflicting data. We considered the electron transport chain as a complex system with mitochondrial membrane potential as an integrative indicator for mitochondrial fitness. METHODS: Twenty-five IPD patients (nine females; mean disease duration, 6.2 years) and 16 healthy age-matched controls (12 females) were recruited. Live platelets were purified using magnetic-activated cell sorting (MACS) and single-cell data on mitochondrial membrane potential (Deltapsi) were measured by cytometry and challenged with a protonophore agent. RESULTS: Functional mitochondrial membrane potential was detected in all participants. The challenge test reduced the membrane potential in all IPD patients and controls (P < 0.001). However, the response to the challenge was not significantly different between patients and controls. INTERPRETATION: While the reported protonophore challenge assay is a valid marker of overall mitochondrial function in live platelets, intact mitochondrial membrane potential in platelets derived from IPD patients suggests that presumed mitochondrial enzymatic deficiencies are compensable in this cell type. In consequence, mitochondrial membrane potential in platelets cannot be used as a diagnostic biomarker for nonstratified IPD but should be further explored in potential Parkinson's disease subtypes and tissues with higher energy demands. [less ▲]

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See detailSystems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson’s disease
Krishna, Abhimanyu UL; Biryukov, Maria UL; Trefois, Christophe UL et al

in BMC Genomics (2014), 15(1154),

Background: The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often ... [more ▼]

Background: The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often used as a cellular model for Parkinson’s disease, the relevance of this cellular model in the context of Parkinson’s disease (PD) and other neurodegenerative diseases has not yet been systematically evaluated. Results: We have used a systems genomics approach to characterize the SH-SY5Y cell line using whole-genome sequencing to determine the genetic content of the cell line and used transcriptomics and proteomics data to determine molecular correlations. Further, we integrated genomic variants using a network analysis approach to evaluate the suitability of the SH-SY5Y cell line for perturbation experiments in the context of neurodegenerative diseases, including PD. Conclusions: The systems genomics approach showed consistency across different biological levels (DNA, RNA and protein concentrations). Most of the genes belonging to the major Parkinson’s disease pathways and modules were intact in the SH-SY5Y genome. Specifically, each analysed gene related to PD has at least one intact copy in SH-SY5Y. The disease-specific network analysis approach ranked the genetic integrity of SH-SY5Y as higher for PD than for Alzheimer’s disease but lower than for Huntington’s disease and Amyotrophic Lateral Sclerosis for loss of function perturbation experiments. [less ▲]

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See detailReproducible Research Results R3
Trefois, Christophe UL; Jarosz, Yohan UL; Gu, Wei UL et al

Poster (2014, December)

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See detailDetection and characterization of critical transitions in mitochondrial activity via high content screening
Trefois, Christophe UL

Doctoral thesis (2014)

Critical transitions exist in many dynamical systems, ranging from the Earth’s cli- mate system to microcosm populations. During a critical transition, the state of a dynamical system abruptly changes ... [more ▼]

Critical transitions exist in many dynamical systems, ranging from the Earth’s cli- mate system to microcosm populations. During a critical transition, the state of a dynamical system abruptly changes from one stable state to another, typically without obvious prior warning. Preventing such abrupt changes remains a chal- lenge, however recently, several metrics were suggested as early warning signals. These indicators are thought to have predictive value for upcoming critical transi- tions. In Parkinson’s disease, there are no detectable motor symptoms in a patient until neuronal dopaminergic cell death exceeds 60–70%. Being able to define early warning signals in a disease context could open new avenues for both preventive and disease modifying treatments. We hypothesize that the dynamics of progression of some disorders including Parkinson’s disease could be manifested by critical tran- sitions. However, before rushing into medical applications, a thorough framework needs to be developed that aims to describe such nonlinear dynamics in cellular systems. In this thesis, we set out to study critical transitions in a simple cellular model using mitochondrial membrane potential ∆Ψ m as readout. To identify criti- cal transitions, we established a modular high-content screening platform allowing systematic perturbation of oxidative phosphorylation. To increase the probability for detecting a critical transition in ∆Ψ m , five inhibitory compounds were combined in multiple pairwise concentration landscapes. We show that critical transitions, de- tectable via ∆Ψ m , are an intrinsic property of the cellular system studied and that two-component Gaussian mixture models adequately capture the dynamics of the critical transition occurring for the combination of Oligomycin A and Antimycin A. Adding to that, we identified the coefficient of variation as a strong early warning signal for the upcoming of the critical transitions. This thesis should serve as a foundation for a broader application of critical transitions and early warning sig- nals in both cell culture systems and translational studies aiming to understand the nonlinear dynamics of biological systems. [less ▲]

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See detailCuration of complex molecular pathways of Parkinson's disease as a collaborative scientific community effort
Antony, Paul UL; Ostaszewski, Marek UL; Gawron, P et al

Scientific Conference (2014, June 12)

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See detailAutomated nuclei clump splitting by combining local concavity orientation and graph partitioning
Samsi, Siddharth UL; Trefois, Christophe UL; Antony, Paul UL et al

in International Conference on Biomedical and Health Informatics (2014)

Automated clump decomposition is essential for single cell based analysis of fluorescent microscopy images. This paper presents a new method for automatically splitting clumps of cell nuclei in ... [more ▼]

Automated clump decomposition is essential for single cell based analysis of fluorescent microscopy images. This paper presents a new method for automatically splitting clumps of cell nuclei in fluorescence microscopy images. Nuclei are first segmented using histogram concavity analysis. Clumps of nuclei are detected by fitting an ellipse to the segmented objects and examining objects where the fitted ellipse does not overlap accurately with the segmented object. These clumps are then further processed to find concave points on the object boundaries. The orientation of the detected concavities is subsequently calculated based on the local shape of the object border. Finally, a graph segmentation based approach is used to pair concavities that represent best candidates for splitting touching nuclei based on properties derived from the local concavity properties. This approach was validated by manual inspection and has shown promising results in the high throughput analysis of HeLa cell images. [less ▲]

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See detailIntegrating Pathways of Parkinson's Disease in a Molecular Interaction Map
Fujita, Kazuhiro A.; Ostaszewski, Marek UL; Matsuoka, Yukiko et al

in Molecular Neurobiology (2014)

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is ... [more ▼]

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map . [less ▲]

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See detailThe Parkinson’s Disease Map: a framework for integration, curation and exploration of disease related pathways
Trefois, Christophe UL

Scientific Conference (2013, April 12)

The pathogenesis of Parkinson's Disease (PD) is multi-factorial and age-related, implicating various genetic and environmental factors. It becomes increasingly important to develop new approaches to ... [more ▼]

The pathogenesis of Parkinson's Disease (PD) is multi-factorial and age-related, implicating various genetic and environmental factors. It becomes increasingly important to develop new approaches to organize and explore the exploding knowledge of this field. The published knowledge on pathways implicated in PD, such as synaptic and mitochondrial dysfunction, alpha-synuclein pathobiology, failure of protein degradation systems and neuroinflammation has been organized and represented using CellDesigner. This repository has been linked to a framework of bioinformatics tools including text mining, database annotation, large-scale data integration and network analysis. We present the PD map, a computer-based knowledge repository, which includes molecular mechanisms of PD in a visually structured and standardized way. A bioinformatics framework that facilitates in-depth knowledge exploration, extraction and curation supports the map. We discuss the insights gained from PD map-driven text mining of a corpus of over 50 thousands full text PD-related papers, integration and visualization of gene expression in post mortem brain tissue of PD patients with the map, as well as results of network analysis. Conclusions: The knowledge repository of disease-related mechanisms provides a global insight into relationships between different pathways and allows considering a given pathology in a broad context. Enrichment with available text and bioinformatics databases as well as integration of experimental data supports better understanding of complex mechanisms of PD and formulation of novel research hypotheses. [less ▲]

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See detailLight microscopy applications in systems biology: opportunities and challenges.
Antony, Paul UL; Trefois, Christophe UL; Stojanovic, Aleksandar UL et al

in Cell Communication and Signaling (2013), 11(1), 1-19

Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various ... [more ▼]

Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various biological scales in living cells. The combination of molecular biology and imaging provides a bottom-up tool for direct insight into how molecular processes work on a cellular scale. However, imaging can also be used as a top-down approach to study the behavior of a system without detailed prior knowledge about its underlying molecular mechanisms. In this review, we highlight the recent developments on microscopy-based systems analyses and discuss the complementary opportunities and different challenges with high-content screening and high-throughput imaging. Furthermore, we provide a comprehensive overview of the available platforms that can be used for image analysis, which enable community-driven efforts in the development of image-based systems biology. [less ▲]

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See detailThe Parkinson's Disease Map: A Framework for Integration, Curation and Exploration of Disease-related Pathways
Ostaszewski, Marek UL; Fujita, Kazuhiro; Matsuoka, Yukiko et al

Poster (2013, March 09)

Objectives: The pathogenesis of Parkinson's Disease (PD) is multi-factorial and age-related, implicating various genetic and environmental factors. It becomes increasingly important to develop new ... [more ▼]

Objectives: The pathogenesis of Parkinson's Disease (PD) is multi-factorial and age-related, implicating various genetic and environmental factors. It becomes increasingly important to develop new approaches to organize and explore the exploding knowledge of this field. Methods: The published knowledge on pathways implicated in PD, such as synaptic and mitochondrial dysfunction, alpha-synuclein pathobiology, failure of protein degradation systems and neuroinflammation has been organized and represented using CellDesigner. This repository has been linked to a framework of bioinformatics tools including text mining, database annotation, large-scale data integration and network analysis. The interface for online curation of the repository has been established using Payao tool. Results: We present the PD map, a computer-based knowledge repository, which includes molecular mechanisms of PD in a visually structured and standardized way. A bioinformatics framework that facilitates in-depth knowledge exploration, extraction and curation supports the map. We discuss the insights gained from PD map-driven text mining of a corpus of over 50 thousands full text PD-related papers, integration and visualization of gene expression in post mortem brain tissue of PD patients with the map, as well as results of network analysis. Conclusions: The knowledge repository of disease-related mechanisms provides a global insight into relationships between different pathways and allows considering a given pathology in a broad context. Enrichment with available text and bioinformatics databases as well as integration of experimental data supports better understanding of complex mechanisms of PD and formulation of novel research hypotheses. [less ▲]

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See detailDifferentiated SH-SY5Y Cells as PD Model for Mitochondrial Dysfunction: From Whole Genome Sequencing to an Educated Design of High-Throughput Experiments
Antony, Paul UL; Krishna, Abhimanyu UL; May, Patrick UL et al

Poster (2013)

Objectives: Mitochondrial dysfunction is a cellular hallmark of Parkinson's disease (PD) and energetic stress of dopaminergic neurons appears to be a physiological risk factor for mitochondrial ... [more ▼]

Objectives: Mitochondrial dysfunction is a cellular hallmark of Parkinson's disease (PD) and energetic stress of dopaminergic neurons appears to be a physiological risk factor for mitochondrial dysfunction. It is however challenging to assess the high variety of factors regulating mitochondrial physiology in living neurons in a high throughput manner. To overcome this bottleneck, we established an analysis platform, using the neuroblastoma cell line SH-SY5Y. For the first time ever we have characterized the SH-SY5Y cell line in an integrated whole genome, transcriptome, and proteome approach. In addition, we show that neuronal differentiation improves the physiological properties of this experimental model for studying mitochondrial dysfunction in PD. Methods: Whole genome sequencing, RNA-Seq, qRT-PCR, MS, FRET using Voltage sensing proteins, Immunofluorescence, cytometry, and live cell imaging. Results: The integrated molecular characterization of SH-SY5Y uncovers the level of molecular network integrity and hence the relevance of this cell line for targeted studies in selected molecular processes. Furthermore, we dissect changes in mitochondrial and energetic stress factors during the process of neuronal differentiation. Conclusions: In terms of both morphology and energetic stress response, differentiated SH-SY5Y cells are more similar to dopaminergic neurons than their undifferentiated precursors. Thanks to dividing progenitors and the short duration of differentiation, combined with the use of specific endpoints analysed with high-content microscopy, our platform paves the route for high throughput experiments on a neuronal cell culture model for PD. Our genomic characterization and expression profiling of SH-SY5Y cells furthermore helps guiding the experimental design and interpretation of such studies. [less ▲]

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See detailAnalysis of critical transitions in Parkinson's disease
Trefois, Christophe UL; Antony, Paul UL; Baumuratov, Aidos UL et al

Poster (2011, December 12)

Background Parkinson’s disease is the most common neurodegenerative movement disorder and is clinically characterized by resting tremor, bradykinesia and cogwheel rigidity. The disease affects 1-2% of the ... [more ▼]

Background Parkinson’s disease is the most common neurodegenerative movement disorder and is clinically characterized by resting tremor, bradykinesia and cogwheel rigidity. The disease affects 1-2% of the global population with prevalence in the people above 65 years of age. The main pathological hallmark of Parkinson’s disease is a progressive loss of dopaminergic neurons in the substantia nigra. Therefore, one important challenge is to improve the understanding of regime shifts between health and disease states. Improving predictions of critical transitions triggering the onset of parkinsonian phenotypes could contribute to the improvement of preventive treatments. Methods Based on cellular models, we will use the mathematical concept of critical transitions to create a toolbox for potentially predicting tipping points towards cellular Parkinson’s disease phenotypes, e.g. mitochondrial dysfunction. Experimentally, we will induce and analyze potential critical transitions in the SH-SY5Y cell line. To do this, we will apply Parkinson’s disease relevant chemical and genetic perturbations and analyze multiple scales of the resulting temporal system behavior. We will combine high content imaging with genetic and biochemical data. A significant informatics challenge arises from the aim to perform the analysis of high time-resolved 3D imaging data. We are therefore developing an automated image analysis pipeline that relies on latest technologies and techniques, such as 3D deconvolution and 3D particle tracking. This pipeline will be applied to study parameters, such as mitochondrial dynamics, which include for instance velocity, morphology, and spatial organization. [less ▲]

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See detailEfficient Access Control for Wireless Sensor Data
Sorniotti, Alessandro; Molva, Refik; Gomez, Laurent et al

in International Journal of Wireless Information Networks (2009), 6(3), 165--174

Abstract Although very developed in many sectors (databases, filesystems), access control schemes are still somewhat elusive when it comes to wireless sensor net- works. However, it is clear that many WSN ... [more ▼]

Abstract Although very developed in many sectors (databases, filesystems), access control schemes are still somewhat elusive when it comes to wireless sensor net- works. However, it is clear that many WSN systems—such as healthcare and automotive ones—need a controlled access to data that sensor nodes produce, given its high sensitivity. Enforcing access control in wireless sensor networks is a particularly difficult task due to the limited computational capacity of wireless sensor nodes. In this paper we present a full-fledged access control scheme for wireless sensor data. We enforce access control through data encryption, thus embedding access control in sensor data units. We also propose a lightweight key generation mechanism, based on cryptographic hash functions, that allows for hierarchical key derivation. The suggested pro- tocol only relies on simple operations, does not require interactions between nodes and data consumers and has minimal storage requirements. [less ▲]

Detailed reference viewed: 54 (6 UL)