Marek Ostaszewski

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.

Immune anomaly detection enhanced with evolutionary paradigms

The paper presents an approach based on principles of immune systems to the anomaly detection problem. Flexibility and efficiency of the anomaly detection system are achieved by building a model of network behavior based on the self-nonself space paradigm. Covering both self and nonself spaces by hyperrectangular structures is proposed. Structures corresponding to self-space are built using a training set from this space. Hyperrectangular detectors covering nonself space are created using niching genetic algorithm. A coevolutionary algorithm is proposed to enhance this process. Results of experiments show a high quality of intrusion detection, which outperform the quality of recently proposed approach based on hypersphere representation of self-space.

Coevolutionary-based Mechanisms for Network Anomaly Detection

The paper presents an approach based on the principles of immune systems applied to the anomaly detection problem. Flexibility and efficiency of the anomaly detection system are achieved by building a model of the network behavior based on the self–nonself space paradigm. Covering both self and nonself spaces by hyperrectangular structures is proposed. The structures corresponding to self-space are built using a training set from this space. The hyperrectangular detectors covering nonself space are created using a niching genetic algorithm. A coevolutionary algorithm is proposed to enhance this process. The results of experiments show a high quality of intrusion detection, which outperform the quality of the recently proposed approach based on a hypersphere representation of the self-space.

Integration and Visualization of Translational Medicine Data for Better Understanding of Human Diseases

Abstract Translational medicine is a domain turning results of basic life science research into new tools and methods in a clinical environment, for example, as new diagnostics or therapies. Nowadays, the process of translation is supported by large amounts of heterogeneous data ranging from medical data to a whole range of -omics data. It is not only a great opportunity but also a great challenge, as translational medicine big data is difficult to integrate and analyze, and requires the involvement of biomedical experts for the data processing. We show here that visualization and interoperable workflows, combining multiple complex steps, can address at least parts of the challenge. In this article, we present an integrated workflow for exploring, analysis, and interpretation of translational medicine data in the context of human health. Three Web services—tranSMART, a Galaxy Server, and a MINERVA platform—are combined into one big data pipeline. Native visualization capabilities enable the biomedical experts to get a comprehensive overview and control over separate steps of the workflow. The capabilities of tranSMART enable a flexible filtering of multidimensional integrated data sets to create subsets suitable for downstream processing. A Galaxy Server offers visually aided construction of analytical pipelines, with the use of existing or custom components. A MINERVA platform supports the exploration of health and disease-related mechanisms in a contextualized analytical visualization system. We demonstrate the utility of our workflow by illustrating its subsequent steps using an existing data set, for which we propose a filtering scheme, an analytical pipeline, and a corresponding visualization of analytical results. The workflow is available as a sandbox environment, where readers can work with the described setup themselves. Overall, our work shows how visualization and interfacing of big data processing services facilitate exploration, analysis, and interpretation of translational medicine data.

MINERVA—a platform for visualization and curation of molecular interaction networks

Our growing knowledge about various molecular mechanisms is becoming increasingly more structured and accessible. Different repositories of molecular interactions and available literature enable construction of focused and high-quality molecular interaction networks. Novel tools for curation and exploration of such networks are needed, in order to foster the development of a systems biology environment. In particular, solutions for visualization, annotation and data cross-linking will facilitate usage of network-encoded knowledge in biomedical research. To this end we developed the MINERVA (Molecular Interaction NEtwoRks VisuAlization) platform, a standalone webservice supporting curation, annotation and visualization of molecular interaction networks in Systems Biology Graphical Notation (SBGN)-compliant format. MINERVA provides automated content annotation and verification for improved quality control. The end users can explore and interact with hosted networks, and provide direct feedback to content curators. MINERVA enables mapping drug targets or overlaying experimental data on the visualized networks. Extensive export functions enable downloading areas of the visualized networks as SBGN-compliant models for efficient reuse of hosted networks. The software is available under Affero GPL 3.0 as a Virtual Machine snapshot, Debian package and Docker instance at http://r3lab.uni.lu/web/minerva-website/. We believe that MINERVA is an important contribution to systems biology community, as its architecture enables set-up of locally or globally accessible SBGN-oriented repositories of molecular interaction networks. Its functionalities allow overlay of multiple information layers, facilitating exploration of content and interpretation of data. Moreover, annotation and verification workflows of MINERVA improve the efficiency of curation of networks, allowing life-science researchers to better engage in development and use of biomedical knowledge repositories.

Evolutionary conservation and network structure characterize genes of phenotypic relevance for mitosis in human.

The impact of gene silencing on cellular phenotypes is difficult to establish due to the complexity of interactions in the associated biological processes and pathways. A recent genome-wide RNA knock-down study both identified and phenotypically characterized a set of important genes for the cell cycle in HeLa cells. Here, we combine a molecular interaction network analysis, based on physical and functional protein interactions, in conjunction with evolutionary information, to elucidate the common biological and topological properties of these key genes. Our results show that these genes tend to be conserved with their corresponding protein interactions across several species and are key constituents of the evolutionary conserved molecular interaction network. Moreover, a group of bistable network motifs is found to be conserved within this network, which are likely to influence the network stability and therefore the robustness of cellular functioning. They form a cluster, which displays functional homogeneity and is significantly enriched in genes phenotypically relevant for mitosis. Additional results reveal a relationship between specific cellular processes and the phenotypic outcomes induced by gene silencing. This study introduces new ideas regarding the relationship between genotype and phenotype in the context of the cell cycle. We show that the analysis of molecular interaction networks can result in the identification of genes relevant to cellular processes, which is a promising avenue for future research.

A nonself space approach to network anomaly detection

The paper presents an approach for the anomaly detection problem based on principles of immune systems. Flexibility and efficiency of the anomaly detection system are achieved by building a model of network behavior based on self-nonself space paradigm. Covering both self and nonself spaces by hyperrectangular structures is proposed. Structures corresponding to self-space are built using a training set from this space. Hyperrectangular detectors covering nonself space are created using niching genetic algorithm. Coevolutionary algorithm is proposed to enhance this process. Results of conducted experiments show a high quality of intrusion detection which outperforms the quality of recently proposed approach based on hypersphere representation of self-space

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.

Neurological Diseases from a Systems Medicine Point of View

The difficulty to understand, diagnose, and treat neurological disorders stems from the great complexity of the central nervous system on different levels of physiological granularity. The individual components, their interactions, and dynamics involved in brain development and function can be represented as molecular, cellular, or functional networks, where diseases are perturbations of networks. These networks can become a useful research tool in investigating neurological disorders if they are properly tailored to reflect corresponding mechanisms. Here, we review approaches to construct networks specific for neurological disorders describing disease-related pathology on different scales: the molecular, cellular, and brain level. We also briefly discuss cross-scale network analysis as a necessary integrator of these scales.

Multiobjective classification with moGEP: an application in the network traffic domain

The paper proposes a multiobjective approach to the problem of malicious network traffic classification, with specificity and sensitivity criteria as objective functions for the problem. The multiobjective version of Gene Expression Programming (GEP) called moGEP is proposed and applied to find proper classifiers in the multiobjective search space. The purpose of the classifiers is to discriminate information about the network traffic obtained from Idiotypic Network-based Intrusion Detection System (INIDS), transformed into time series. The proposed approach is validated using the network traffic simulator ns2. Classifiers of high accuracy are obtained and their diversity offers interesting possibilities to the domain of network security.