Christophe Trefois

Integrating Pathways of Parkinson's Disease in a Molecular Interaction Map

Parkinsons 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.

Systems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson's disease

BackgroundThe 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.ResultsWe 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.ConclusionsThe 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.

Critical transitions in chronic disease: transferring concepts from ecology to systems medicine

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.

Characterization of Differentiated SH-SY5Y as Neuronal Screening Model Reveals Increased Oxidative Vulnerability

The immortalized and proliferative cell line SH-SY5Y is one of the most commonly used cell lines in neuroscience and neuroblastoma research. However, undifferentiated SH-SY5Y cells share few properties with mature neurons. In this study, we present an optimized neuronal differentiation protocol for SH-SY5Y that requires only two work steps and 6 days. After differentiation, the cells present increased levels of ATP and plasma membrane activity but reduced expression of energetic stress response genes. Differentiation results in reduced mitochondrial membrane potential and decreased robustness toward perturbations with 6-hydroxydopamine. We are convinced that the presented differentiation method will leverage genetic and chemical high-throughput screening projects targeting pathways that are involved in the selective vulnerability of neurons with high energetic stress levels.

Light microscopy applications in systems biology: opportunities and challenges

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.

Efficient Access Control for Wireless Sensor Data

Although very developed in many sectors (databases, filesystems), access control schemes are still somewhat elusive when it comes to wireless sensor networks. 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 protocol only relies on simple operations, does not require interactions between nodes and data consumers and has minimal storage requirements.

Platelet mitochondrial membrane potential in Parkinson's disease

Mitochondrial dysfunction is a hallmark of idiopathic Parkinsons 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.

Encryption-based access control for building management

The vision of ubiquitous computing is a network of small, inexpensive, robust processing devices, distributed throughout everyday life. Wireless Sensor Networks (WSNs) are an essential part to realize this dream. Sensor Networks can be seen as sources of input, delivering data from the real world into the digital world.

Automated nuclei clump splitting by combining local concavity orientation and graph partitioning

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.

Provenance-Enabled Stewardship of Human Data in the GDPR Era

Within life-science research the upcoming EU General Data Protection Regulation has a significant operational impact on organisations that use and exchange controlled-access Human Data. One implication of the GDPR is data bookkeeping. In this poster we describe a software tool, the Data Information System (DAISY), designed to record data protection relevant provenance of Human Data held and exchanged by research organisations.