1,256 research outputs found

    Analysis of metabolomic data: tools, current strategies and future challenges for omics data integration

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    Metabolomics is a rapidly growing field consisting of the analysis of a large number of metabolites at a system scale. The two major goals of metabolomics are the identification of the metabolites characterizing each organism state and the measurement of their dynamics under different situations (e.g. pathological conditions, environmental factors). Knowledge about metabolites is crucial for the understanding of most cellular phenomena, but this information alone is not sufficient to gain a comprehensive view of all the biological processes involved. Integrated approaches combining metabolomics with transcriptomics and proteomics are thus required to obtain much deeper insights than any of these techniques alone. Although this information is available, multilevel integration of different 'omics' data is still a challenge. The handling, processing, analysis and integration of these data require specialized mathematical, statistical and bioinformatics tools, and several technical problems hampering a rapid progress in the field exist. Here, we review four main tools for number of users or provided features (MetaCore(TM), MetaboAnalyst, InCroMAP and 3Omics) out of the several available for metabolomic data analysis and integration with other 'omics' data, highlighting their strong and weak aspects; a number of related issues affecting data analysis and integration are also identified and discussed. Overall, we provide an objective description of how some of the main currently available software packages work, which may help the experimental practitioner in the choice of a robust pipeline for metabolomic data analysis and integration

    Utilising proteomics to understand and define hypertension: where are we and where do we go?

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    Introduction: Hypertension is a complex and multifactorial cardiovascular disorder. With different mechanisms contributing to a different extent to an individual’s blood pressure the discovery of novel pathogenetic principles of hypertension is challenging. However, there is an urgent and unmet clinical need to improve prevention, detection and therapy of hypertension in order to reduce the global burden associated with hypertension-related cardiovascular diseases. Areas covered: Proteomic techniques have been applied in reductionist experimental models including angiotensin II infusion models in rodents and the spontaneously hypertensive rat in order to unravel mechanisms involved in blood pressure control and end organ damage. In humans proteomic studies mainly focus on prediction and detection of organ damage, particularly of heart failure and renal disease. Whilst there are only few proteomic studies specifically addressing human primary hypertension there are more data available in hypertensive disorders in pregnancy such as preeclampsia. We will review these studies and discuss implications of proteomics on precision medicine approaches. Expert commentary: Despite the potential of proteomic studies in hypertension there has been moderate progress in this area of research. Standardised large-scale studies are required in order to make best use of the potential that proteomics offers in hypertension and other cardiovascular diseases

    Simulation and inference algorithms for stochastic biochemical reaction networks: from basic concepts to state-of-the-art

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    Stochasticity is a key characteristic of intracellular processes such as gene regulation and chemical signalling. Therefore, characterising stochastic effects in biochemical systems is essential to understand the complex dynamics of living things. Mathematical idealisations of biochemically reacting systems must be able to capture stochastic phenomena. While robust theory exists to describe such stochastic models, the computational challenges in exploring these models can be a significant burden in practice since realistic models are analytically intractable. Determining the expected behaviour and variability of a stochastic biochemical reaction network requires many probabilistic simulations of its evolution. Using a biochemical reaction network model to assist in the interpretation of time course data from a biological experiment is an even greater challenge due to the intractability of the likelihood function for determining observation probabilities. These computational challenges have been subjects of active research for over four decades. In this review, we present an accessible discussion of the major historical developments and state-of-the-art computational techniques relevant to simulation and inference problems for stochastic biochemical reaction network models. Detailed algorithms for particularly important methods are described and complemented with MATLAB implementations. As a result, this review provides a practical and accessible introduction to computational methods for stochastic models within the life sciences community

    Multiomics integration-based molecular characterizations of COVID-19

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    The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly became a global health challenge, leading to unprecedented social and economic consequences. The mechanisms behind the pathogenesis of SARS-CoV-2 are both unique and complex. Omics-scale studies are emerging rapidly and offer a tremendous potential to unravel the puzzle of SARS-CoV-2 pathobiology, as well as moving forward with diagnostics, potential drug targets, risk stratification, therapeutic responses, vaccine development and therapeutic innovation. This review summarizes various aspects of understanding multiomics integration-based molecular characterizations of COVID-19, which to date include the integration of transcriptomics, proteomics, genomics, lipidomics, immunomics and metabolomics to explore virus targets and developing suitable therapeutic solutions through systems biology tools. Furthermore, this review also covers an abridgment of omics investigations related to disease pathogenesis and virulence, the role of host genetic variation and a broad array of immune and inflammatory phenotypes contributing to understanding COVID-19 traits. Insights into this review, which combines existing strategies and multiomics integration profiling, may help further advance our knowledge of COVID-19.Peer reviewe

    Multiplexed and scalable super-resolution imaging of three-dimensional protein localization in size-adjustable tissues

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    The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnified analysis of the proteome (MAP), linearly expands entire organs fourfold while preserving their overall architecture and three-dimensional proteome organization. MAP is based on the observation that preventing crosslinking within and between endogenous proteins during hydrogel-tissue hybridization allows for natural expansion upon protein denaturation and dissociation. The expanded tissue preserves its protein content, its fine subcellular details, and its organ-scale intercellular connectivity. We use off-the-shelf antibodies for multiple rounds of immunolabeling and imaging of a tissue's magnified proteome, and our experiments demonstrate a success rate of 82% (100/122 antibodies tested). We show that specimen size can be reversibly modulated to image both inter-regional connections and fine synaptic architectures in the mouse brain.United States. National Institutes of Health (1-U01-NS090473-01

    Personalized medicine—a modern approach for the diagnosis and management of hypertension

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    The main goal of treating hypertension is to reduce blood pressure to physiological levels and thereby prevent risk of cardiovascular disease and hypertension-associated target organ damage. Despite reductions in major risk factors and the availability of a plethora of effective antihypertensive drugs, the control of blood pressure to target values is still poor due to multiple factors including apparent drug resistance and lack of adherence. An explanation for this problem is related to the current reductionist and ‘trial-and-error’ approach in the management of hypertension, as we may oversimplify the complex nature of the disease and not pay enough attention to the heterogeneity of the pathophysiology and clinical presentation of the disorder. Taking into account specific risk factors, genetic phenotype, pharmacokinetic characteristics, and other particular features unique to each patient, would allow a personalized approach to managing the disease. Personalized medicine therefore represents the tailoring of medical approach and treatment to the individual characteristics of each patient and is expected to become the paradigm of future healthcare. The advancement of systems biology research and the rapid development of high-throughput technologies, as well as the characterization of different –omics, have contributed to a shift in modern biological and medical research from traditional hypothesis-driven designs toward data-driven studies and have facilitated the evolution of personalized or precision medicine for chronic diseases such as hypertension

    Wine Science in the Omics Era: The Impact of Systems Biology on the Future of Wine Research

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    Industrial wine making confronts viticulturalists, wine makers, process engineers and scientists alike with a bewilderingarray of independent and semi-independent parameters that can in many cases only be optimized by trial and error.Furthermore, as most parameters are outside of individual control, predictability and consistency of the end productremain difficult to achieve. The traditional wine sciences of viticulture and oenology have been accumulating data setsand generating knowledge and know-how that has resulted in a significant optimization of the vine growing and winemaking processes. However, much of these processes remain based on empirical and even anecdotal evidence, andonly a small part of all the interactions and cause-effect relationships between individual input and output parametersis scientifically well understood. Indeed, the complexity of the process has prevented a deeper understanding of suchinteractions and causal relationships. New technologies and methods in the biological and chemical sciences, combinedwith improved tools of multivariate data analysis, open new opportunities to assess the entire vine growing and winemaking process from a more holistic perspective. This review outlines the current efforts to use the tools of systemsbiology in particular to better understand complex industrial processes such as wine making

    The State of the Art in Multilayer Network Visualization

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    Modelling relationship between entities in real-world systems with a simple graph is a standard approach. However, realityis better embraced as several interdependent subsystems (or layers). Recently, the concept of a multilayer network model hasemerged from the field of complex systems. This model can be applied to a wide range of real-world data sets. Examples ofmultilayer networks can be found in the domains of life sciences, sociology, digital humanities and more. Within the domainof graph visualization, there are many systems which visualize data sets having many characteristics of multilayer graphs.This report provides a state of the art and a structured analysis of contemporary multilayer network visualization, not only forresearchers in visualization, but also for those who aim to visualize multilayer networks in the domain of complex systems, as wellas those developing systems across application domains. We have explored the visualization literature to survey visualizationtechniques suitable for multilayer graph visualization, as well as tools, tasks and analytic techniques from within applicationdomains. This report also identifies the outstanding challenges for multilayer graph visualization and suggests future researchdirections for addressing them

    Die Integration von Multiskalen- und Multi-Omik-Daten zur Erforschung von Wirt-Pathogen-Interaktionen am Beispiel von pathogenen Pilzen

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    The ongoing development and improvement of novel measurement techniques for scientific research result in a huge amount of available data coming from hetero- geneous sources. Amongst others, these sources comprise diverse temporal and spatial scales including different omics levels. The integration of such multiscale and multi-omics data enables a comprehensive understanding of the complexity and dynamics of biological systems and their processes. However, due to the biologically and methodically induced data heterogeneity, the integration process is a well-known challenge in nowadays life science. Applying several computational integration approaches, the present doctoral thesis aimed at gaining new insights into the field of infection biology regarding host- pathogen interactions. In this context, the focus was on fungal pathogens causing a variety of local and systemic infections. Based on current examples of research, on the one hand, several well-established approaches for the analysis of multiscale and multi- omics data have been presented. On the other hand, the novel ModuleDiscoverer approach was introduced to identify regulatory modules in protein-protein interac- tion networks. It has been shown that ModuleDiscoverer effectively supports the integration of multi-omics data and, in addition, allows the detection of potential key factors that cannot be detected by other classical approaches. This thesis provides deeper insights into the complex relationships and dynamics of biological systems and, thus, represents an important contribution to the investigation of host-pathogen interactions. Due to the interactions complexity and the limitations of the currently available knowledge databases as well as the bioinformatic tools, further research is necessary to gain a comprehensive understanding of the complexity of biological systems
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