4 research outputs found

    Bridging data management platforms and visualization tools to enable ad-hoc and smart analytics in life sciences

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    Core facilities have to offer technologies that best serve the needs of their users and provide them a competitive advantage in research. They have to set up and maintain instruments in the range of ten to a hundred, which produce large amounts of data and serve thousands of active projects and customers. Particular emphasis has to be given to the reproducibility of the results. More and more, the entire process from building the research hypothesis, conducting the experiments, doing the measurements, through the data explorations and analysis is solely driven by very few experts in various scientific fields. Still, the ability to perform the entire data exploration in real-time on a personal computer is often hampered by the heterogeneity of software, the data structure formats of the output, and the enormous data sizes. These impact the design and architecture of the implemented software stack. At the Functional Genomics Center Zurich (FGCZ), a joint state-of-the-art research and training facility of ETH Zurich and the University of Zurich, we have developed the B-Fabric system, which has served for more than a decade, an entire life sciences community with fundamental data science support. In this paper, we sketch how such a system can be used to glue together data (including metadata), computing infrastructures (clusters and clouds), and visualization software to support instant data exploration and visual analysis. We illustrate our in-daily life implemented approach using visualization applications of mass spectrometry data

    Grape ASR-Silencing Sways Nuclear Proteome, Histone Marks and Interplay of Intrinsically Disordered Proteins

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    In order to unravel the functions of ASR (Abscisic acid, Stress, Ripening-induced) proteins in the nucleus, we created a new model of genetically transformed grape embryogenic cells by RNAi-knockdown of grape ASR (VvMSA). Nuclear proteomes of wild-type and VvMSA-RNAi grape cell lines were analyzed by quantitative isobaric tagging (iTRAQ 8-plex). The most significantly up- or down-regulated nuclear proteins were involved in epigenetic regulation, DNA replication/repair, transcription, mRNA splicing/stability/editing, rRNA processing/biogenesis, metabolism, cell division/differentiation and stress responses. The spectacular up-regulation in VvMSA-silenced cells was that of the stress response protein VvLEA D-29 (Late Embryogenesis Abundant). Both VvMSA and VvLEA D-29 genes displayed strong and contrasted responsiveness to auxin depletion, repression of VvMSA and induction of VvLEA D-29. In silico analysis of VvMSA and VvLEA D-29 proteins highlighted their intrinsically disordered nature and possible compensatory relationship. Semi-quantitative evaluation by medium-throughput immunoblotting of eighteen post-translational modifications of histones H3 and H4 in VvMSA-knockdown cells showed significant enrichment/depletion of the histone marks H3K4me1, H3K4me3, H3K9me1, H3K9me2, H3K36me2, H3K36me3 and H4K16ac. We demonstrate that grape ASR repression differentially affects members of complex nucleoprotein structures and may not only act as molecular chaperone/transcription factor, but also participates in plant responses to developmental and environmental cues through epigenetic mechanisms

    Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4+ T Cells in Multiple Sclerosis

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    Immune responses to citrullinated peptides have been described in autoimmune diseases like rheumatoid arthritis (RA) and multiple sclerosis (MS). We investigated the post-translational modification (PTM), arginine to citrulline, in brain tissue of MS patients and controls (C) by proteomics and subsequently the cellular immune response of cerebrospinal fluid (CSF)-infiltrating T cells to citrullinated and unmodified peptides of myelin basic protein (MBP). Using specifically adapted tissue extraction- and combined data interpretation protocols we could establish a map of citrullinated proteins by identifying more than 80 proteins with two or more citrullinated peptides in human brain tissue. We report many of them for the first time. For the already described citrullinated proteins MBP, GFAP, and vimentin, we could identify additional citrullinated sites. The number of modified proteins in MS white matter was higher than control tissue. Citrullinated peptides are considered neoepitopes that may trigger autoreactivity. We used newly identified epitopes and previously reported immunodominant myelin peptides in their citrullinated and non-citrullinated form to address the recognition of CSF-infiltrating CD4+ T cells from 22 MS patients by measuring proliferation and IFN-Îł secretion. We did not detect marked responses to citrullinated peptides, but slightly more strongly to the non-modified version. Based on these data, we conclude that citrullination does not appear to be an important activating factor of a T cell response, but could be the consequence of an immune- or inflammatory response. Our approach allowed us to perform a deep proteome analysis and opens new technical possibilities to analyze complex PTM patterns on minute quantities of rare tissue samples

    FCC – An automated rule-based processing tool for life science data

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    BACKGROUND: Data processing in the bioinformatics field often involves the handling of diverse software programs in one workflow. The field is lacking a set of standards for file formats so that files have to be processed in different ways in order to make them compatible to different analysis programs. The problem is that mass spectrometry vendors at most provide only closed-sourceWindows libraries to programmatically access their proprietary binary formats. This prohibits the creation of an efficient and unified tool that fits all processing needs of the users. Therefore, researchers are spending a significant amount of time using GUI-based conversion and processing programs. Besides the time needed for manual usage, such programs also can show long running times for processing, because most of them make use of only a single CPU. In particular, algorithms to enhance data quality, e.g. peak picking or deconvolution of spectra, add waiting time for the users. RESULTS: To automate these processing tasks and let them run continuously without user interaction, we developed the FGCZ Converter Control (FCC) at the Functional Genomics Center Zurich (FGCZ) core facility. The FCC is a rule-based system for automated file processing that reduces the operation of diverse programs to a single configuration task. Using filtering rules for raw data files, the parameters for all tasks can be custom-tailored to the needs of every single researcher and processing can run automatically and efficiently on any number of servers in parallel using all available CPU resources. CONCLUSIONS: FCC has been used intensively at FGCZ for processing more than hundred thousand mass spectrometry raw files so far. Since we know that many other research facilities have similar problems, we would like to report on our tool and the accompanying ideas for an efficient set-up for potential reuse
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