100 research outputs found

    Protter: interactive protein feature visualization and integration with experimental proteomic data

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    Summary: The ability to integrate and visualize experimental proteomic evidence in the context of rich protein feature annotations represents an unmet need of the proteomics community. Here we present Protter, a web-based tool that supports interactive protein data analysis and hypothesis generation by visualizing both annotated sequence features and experimental proteomic data in the context of protein topology. Protter supports numerous proteomic file formats and automatically integrates a variety of reference protein annotation sources, which can be readily extended via modular plug-ins. A built-in export function produces publication-quality customized protein illustrations, also for large datasets. Visualizations of surfaceome datasets show the specific utility of Protter for the integrated visual analysis of membrane proteins and peptide selection for targeted proteomics. Availability and implementation: The Protter web application is available at http://wlab.ethz.ch/protter. Source code and installation instructions are available at http://ulo.github.io/Protter/. Contact: [email protected] Supplementary Information: Supplementary data are available at Bioinformatics onlin

    Reversibilität und Irreversibilität: mathematische Untersuchungen zum Zeitverhalten des Produktlebenszyklus

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    Genaue Prognosen von Absatzmöglichkeiten und Marktpotenzialen für Innovationen können heute ein entscheidender Faktor sein, um sich auf dem Markt zu behaupten. Zur Sicherung des langfristigen Unternehmenserfolgs sind im Zeitablauf produkt- und sortimentspolitische Entscheidungen zu treffen. Erst im Zeitablauf wird aber sichtbar, ob sie richtig waren. Betriebswirtschaftlich sind solche irreversiblen Prozesse von großer Bedeutung, deren Umkehr nur indirekt erlaubt (dynamische Irreversibilität) oder sogar unmöglich (technische Irreversibilität) ist. Ohne diese Beschränkungen, spricht man von reversiblen Entscheidungen. Die Ausbreitung von Innovationen in der Literatur erklären lineare, exponentielle und logistische Modelle. Zur Bestimmung des Zeitverhaltens werden die Innovationsausbreitungen mathematisch in Hin- und Rückrichtung berechnet und klassifiziert. Die Simulation der Zeitumkehr erfolgt durch Änderung der Vorzeichen für den Innovationskoeffizienten (Antiwerbung) und Imitationskoeffizienten (negative Mundpropaganda) in den Diffusionsgleichungen. Im Ergebnis zeigt sich, dass logistische und exponentielle Diffusionsprozesse dynamisch irreversibel sind. Technische Irreversibilität tritt hingegen nur für logistische Ausbreitungsvorgänge auf. -- Produktlebenszyklus ; Innovationsmanagement ; DynamicAccurate forecasts of sales opportunities and market potential for innovation can now be a crucial factor in order to compete in the market. To secure the long-term business success is over time and product-range policy decisions. Over time, this would not be identified whether they were correct. Economically such irreversible processes are of great importance, that reversal may only indirectly (dynamic irreversibility) or even impossible (technical irreversibility) is. Without these restrictions, it is called reversible decisions. The spread of innovations explained in the literature, linear, exponential and logistic models. To determine the time behavior of the innovation propagation are mathematically calculated in return direction and classified. The simulation time is reversed by changing the sign for the coefficient of innovation (anti-advertising) and imitation coefficients (negative word of mouth) in the diffusion equations. The results show that logistic and exponential diffusion processes are dynamic irreversible. Technical irreversibility occurs only for logistical propagation processes

    Birth Order, Caesarean Section, or Daycare Attendance in Relation to Child- and Adult-Onset Type 1 Diabetes: Results from the German National Cohort

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    Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection

    An Integrated Systems Approach Unveils New Aspects of Microoxia-Mediated Regulation in Bradyrhizobium diazoefficiens

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    The adaptation of rhizobia from the free-living state in soil to the endosymbiotic state comprises several physiological changes in order to cope with the extremely low oxygen availability (microoxia) within nodules. To uncover cellular functions required for bacterial adaptation to microoxia directly at the protein level, we applied a systems biology approach on the key rhizobial model and soybean endosymbiont Bradyrhizobium diazoefficiens USDA 110 (formerly B. japonicum USDA 110). As a first step, the complete genome of B. diazoefficiens 110spc4, the model strain used in most prior functional genomics studies, was sequenced revealing a deletion of a ~202 kb fragment harboring 223 genes and several additional differences, compared to strain USDA 110. Importantly, the deletion strain showed no significantly different phenotype during symbiosis with several host plants, reinforcing the value of previous OMICS studies. We next performed shotgun proteomics and detected 2,900 and 2,826 proteins in oxically and microoxically grown cells, respectively, largely expanding our knowledge about the inventory of rhizobial proteins expressed in microoxia. A set of 62 proteins was significantly induced under microoxic conditions, including the two nitrogenase subunits NifDK, the nitrogenase reductase NifH, and several subunits of the high-affinity terminal cbb3 oxidase (FixNOQP) required for bacterial respiration inside nodules. Integration with the previously defined microoxia-induced transcriptome uncovered a set of 639 genes or proteins uniquely expressed in microoxia. Finally, besides providing proteogenomic evidence for novelties, we also identified proteins with a regulation similar to that of FixK2: transcript levels of these protein-coding genes were significantly induced, while the corresponding protein abundance remained unchanged or was down-regulated. This suggested that, apart from fixK2, additional B. diazoefficiens genes might be under microoxia-specific post-transcriptional control. This hypothesis was indeed confirmed for several targets (HemA, HemB, and ClpA) by immunoblot analysis

    An integrative strategy to identify the entire protein coding potential of prokaryotic genomes by proteogenomics

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    Accurate annotation of all protein-coding sequences (CDSs) is an essential prerequisite to fully exploit the rapidly growing repertoire of completely sequenced prokaryotic genomes. However, large discrepancies among the number of CDSs annotated by different resources, missed functional short open reading frames (sORFs), and overprediction of spurious ORFs represent serious limitations. Our strategy toward accurate and complete genome annotation consolidates CDSs from multiple reference annotation resources, ab initio gene prediction algorithms and in silico ORFs (a modified six-frame translation considering alternative start codons) in an integrated proteogenomics database (iPtgxDB) that covers the entire protein-coding potential of a prokaryotic genome. By extending the PeptideClassifier concept of unambiguous peptides for prokaryotes, close to 95% of the identifiable peptides imply one distinct protein, largely simplifying downstream analysis. Searching a comprehensive Bartonella henselae proteomics data set against such an iPtgxDB allowed us to unambiguously identify novel ORFs uniquely predicted by each resource, including lipoproteins, differentially expressed and membrane-localized proteins, novel start sites and wrongly annotated pseudogenes. Most novelties were confirmed by targeted, parallel reaction monitoring mass spectrometry, including unique ORFs and single amino acid variations (SAAVs) identified in a re-sequenced laboratory strain that are not present in its reference genome. We demonstrate the general applicability of our strategy for genomes with varying GC content and distinct taxonomic origin. We release iPtgxDBs for B. henselae, Bradyrhizobium diazoefficiens and Escherichia coli and the software to generate both proteogenomics search databases and integrated annotation files that can be viewed in a genome browser for any prokaryote

    Perfluorocarbon Particle Size Influences Magnetic Resonance Signal and Immunological Properties of Dendritic Cells

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    The development of cellular tracking by fluorine (19F) magnetic resonance imaging (MRI) has introduced a number of advantages for following immune cell therapies in vivo. These include improved signal selectivity and a possibility to correlate cells labeled with fluorine-rich particles with conventional anatomic proton (1H) imaging. While the optimization of the cellular labeling method is clearly important, the impact of labeling on cellular dynamics should be kept in mind. We show by 19F MR spectroscopy (MRS) that the efficiency in labeling cells of the murine immune system (dendritic cells) by perfluoro-15-crown-5-ether (PFCE) particles increases with increasing particle size (560>365>245>130 nm). Dendritic cells (DC) are professional antigen presenting cells and with respect to impact of PFCE particles on DC function, we observed that markers of maturation for these cells (CD80, CD86) were also significantly elevated following labeling with larger PFCE particles (560 nm). When labeled with these larger particles that also gave an optimal signal in MRS, DC presented whole antigen more robustly to CD8+ T cells than control cells. Our data suggest that increasing particle size is one important feature for optimizing cell labeling by PFCE particles, but may also present possible pitfalls such as alteration of the immunological status of these cells. Therefore depending on the clinical scenario in which the 19F-labeled cellular vaccines will be applied (cancer, autoimmune disease, transplantation), it will be interesting to monitor the fate of these cells in vivo in the relevant preclinical mouse models
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