In specific contract No 2 issued under the framework agreement OC/EFSA/AMU/2019/02, EFSA requeste... more In specific contract No 2 issued under the framework agreement OC/EFSA/AMU/2019/02, EFSA requested Open Analytics to implement a web application for collecting information on using Critical Appraisal Tools (CAT). The web application has three modules: one for managing purposes, one for viewing the data and one with the actual survey. Visibility of these modules is defined according the type of user that has logged into the web application. There are two user types: (1) AMU Level, able to add/edit records; (2) EFSA Level, able to view all records. The visualization module is accessible by all users with the same functionalities, while the manage and survey page are only visible to AMU users. Data are stored on a shared docker volume which allows all users to view the latest available data.
In specific contract No 5 issued under the framework agreement OC/EFSA/AMU/2015/02, EFSA requeste... more In specific contract No 5 issued under the framework agreement OC/EFSA/AMU/2015/02, EFSA requested Open Analytics to implement software for analysing and visualizing spatio-temporal data. In the exploratory analysis, local statistics (Moran's I and Geary's C) help to recognize potential clusters and hotspots. Smoothed predictions over space and time can be calculated and visualized using ordinary kriging. Logistic regression models allow to include spatial and temporal effects, spatiotemporal interactions and potential covariates. These models are either Bayesian hierarchical models or generalized additive models and several model structures can be compared using model diagnostics. Summary measures for the estimated response values can be visualized over space and time. An interactive component guides the user in uploading data, performing an exploratory analysis and fitting spatio-temporal models.
In specific contract No 7 issued under the framework agreement OC/EFSA/AMU/2015/02, EFSA requeste... more In specific contract No 7 issued under the framework agreement OC/EFSA/AMU/2015/02, EFSA requested Open Analytics to extend the Web application for Benchmark Dose Modelling built under specific contracts No 3 and No 4. The Web application is further developed in R with focus on creating a graphical module to evaluate model fit and to modify specific plot settings, as specified in the Technical Annex to Specific Contract No 7. The web application includes the latest developments in PROAST on model averaging for litter quantal data, fitting single models and extending the work on quantal data to ordinal data. The contractor explores in conjunction with EFSA the extension of model families for continuous data, study the recommended number of runs in the model averaging process as well as the performance of model averaging in this context. The module includes the possibility to run analysis on several endpoints and provides a summary comparing results.
Work Package 3 of SafetyNet deals with Safety Performance Indicators. They measure the operationa... more Work Package 3 of SafetyNet deals with Safety Performance Indicators. They measure the operational conditions of the road traffic system. Work Package 3 deals with seven topics: alcohol and drug use; speeds; protective systems; daytime running lights; vehicles; road; trauma management. This deliverable concerns the contribution of Work Package 3 to the first SafetyNet conference, which was held in Prague on May 10 and 11, 2006. Each topic prepared a poster with an overview of the state-of-play. In this document, these posters are assembled. Each topic has a preferred indicator, which can be used for measuring safety performance across countries. This indicator is accompanied by requirements that should be met by the data, in order to be able to calculate the indicator. For most tasks, values could be calculated for the indicators by using the available data. Data are not available for all countries and/or all topics.
To predict human pharmacokinetics (PK) such as the clearance and the plasma concentration profile... more To predict human pharmacokinetics (PK) such as the clearance and the plasma concentration profile of a new compound many animal-based methods have been used in the past. They are typically based on animal information of the compound of interest only (Mahmood 2005). This step translational is crucial in pharmaceutical development since it is used to estimate the human pharmacokinetics parameters
Upon maturation, primary neuronal cultures form an interconnected network based on neurite outgro... more Upon maturation, primary neuronal cultures form an interconnected network based on neurite outgrowth and synaptogenesis in which spontaneous electrical activity arises. Measurement of network activity allows quantification of neuronal health and maturation. A fluorescent indicator was used to monitor secondary calcium influxes after the occurrence of action potentials, allowing us to examine activity of hippocampal cultures via confocal live cell imaging. Subsequently, nuclear staining with DAPI allows accurate cell segmentation. To analyze the calcium recording in a robust, observer-independent manner, we implemented an automated image- and signal-processing algorithm and validated it against a visual, interactive procedure. Both methods yielded similar results on the emergence of synchronized activity and allowed robust quantitative measurement of acute and chronic modulation of drugs on network activity. Both the number of days in vitro (DIV) and neutralization of nerve growth factor (NGF) have a significant effect on synchronous burst frequency and correlation. Acute effects are demonstrated using 5-HT (serotonin) and ethylene glycol tetra-acetic acid. Automated analysis allowed measuring additional features, such as peak decay times and bursting frequency of individual neurons. Based on neuronal cell cultures in 96-well plates and accurate calcium recordings, the analysis method allows development of an integrated high-content screening assay. Because molecular biological techniques can be applied to assess the influence of genes on network activity, it is applicable for neurotoxicity or neurotrophics screening as well as development of in vitro disease models via, for example, pharmacologic manipulation or RNAi.
Maintainer Setia Pramana <[email protected]> Description The IsoGene Graphical User Inter... more Maintainer Setia Pramana <[email protected]> Description The IsoGene Graphical User Interface (IsoGene-GUI) is a user friendly inter-face of the IsoGene package which is aimed to identify for genes with a mono-tonic trend in the expression levels with respect to the increasing doses using several test statis-tics: global likelihood ratio test (E2), Bartholomew 1961, Barlow et al. 1972 and Robert-son et al. 1988), Williams (1971, 1972), Marcus (1976), the M (Hu et al. 2005) and the modi-fied M (Lin et al. 2007). The p-values of the global likelihood ratio test (E2) are obtained us-ing the excat distribution and permutation. The other four test statistics are obtained using per-mutation . Several p-values adjustment are provided: Bonfer-roni, Holm (1979), Hochberg (1988), and Sidak procedures for controlling the family-wise Type I error rate (FWER), and BH (Benjamini and Hochberg 1995) and BY (Ben-jamini and Yekutieli 2001) procedures are used for controlling the FDR. the infe...
Background: Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infect... more Background: Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infections, followed by lifelong nonpathogenic persistence. HPyV, and specifically JCPyV, are known to co-diverge with their host, implying a slow rate of viral evolution and a large timescale of virus/host co-existence. Recent bio-informatic reports showed a large level of peptide homology between JCPyV and the human proteome. In this study, the antibody response to PyV peptides is evaluated. Methods: The in-silico analysis of the HPyV proteome was followed by peptide microarray serology. A HPyV-peptide microarray containing 4,284 peptides was designed and covered 10 polyomavirus proteomes. Plasma samples from 49 healthy subjects were tested against these peptides. Results: In-silico analysis of all possible HPyV 5-mer amino acid sequences were compared to the human proteome, and 1,609 unique motifs are presented. Assuming a linear epitope being as small as a pentapeptide, on average 9.3% of the polyomavirus proteome is unique and could be recognized by the host as non-self. Small t Ag (stAg) contains a significantly higher percentage of unique pentapeptides. Experimental evidence for the presence of antibodies against HPyV 15-mer peptides in healthy subjects resulted in the following observations: i) antibody responses against stAg were significantly elevated, and against viral protein 2 (VP2) significantly reduced; and ii) there was a significant correlation between the increasing number of embedded unique HPyV penta-peptides and the increase in microarray fluorescent signal. Conclusion: The anti-peptide HPyV-antibodies in healthy subjects are preferably directed against the penta-peptide derived unique fraction of the viral proteome.
In specific contract No 2 issued under the framework agreement OC/EFSA/AMU/2019/02, EFSA requeste... more In specific contract No 2 issued under the framework agreement OC/EFSA/AMU/2019/02, EFSA requested Open Analytics to implement a web application for collecting information on using Critical Appraisal Tools (CAT). The web application has three modules: one for managing purposes, one for viewing the data and one with the actual survey. Visibility of these modules is defined according the type of user that has logged into the web application. There are two user types: (1) AMU Level, able to add/edit records; (2) EFSA Level, able to view all records. The visualization module is accessible by all users with the same functionalities, while the manage and survey page are only visible to AMU users. Data are stored on a shared docker volume which allows all users to view the latest available data.
In specific contract No 5 issued under the framework agreement OC/EFSA/AMU/2015/02, EFSA requeste... more In specific contract No 5 issued under the framework agreement OC/EFSA/AMU/2015/02, EFSA requested Open Analytics to implement software for analysing and visualizing spatio-temporal data. In the exploratory analysis, local statistics (Moran's I and Geary's C) help to recognize potential clusters and hotspots. Smoothed predictions over space and time can be calculated and visualized using ordinary kriging. Logistic regression models allow to include spatial and temporal effects, spatiotemporal interactions and potential covariates. These models are either Bayesian hierarchical models or generalized additive models and several model structures can be compared using model diagnostics. Summary measures for the estimated response values can be visualized over space and time. An interactive component guides the user in uploading data, performing an exploratory analysis and fitting spatio-temporal models.
In specific contract No 7 issued under the framework agreement OC/EFSA/AMU/2015/02, EFSA requeste... more In specific contract No 7 issued under the framework agreement OC/EFSA/AMU/2015/02, EFSA requested Open Analytics to extend the Web application for Benchmark Dose Modelling built under specific contracts No 3 and No 4. The Web application is further developed in R with focus on creating a graphical module to evaluate model fit and to modify specific plot settings, as specified in the Technical Annex to Specific Contract No 7. The web application includes the latest developments in PROAST on model averaging for litter quantal data, fitting single models and extending the work on quantal data to ordinal data. The contractor explores in conjunction with EFSA the extension of model families for continuous data, study the recommended number of runs in the model averaging process as well as the performance of model averaging in this context. The module includes the possibility to run analysis on several endpoints and provides a summary comparing results.
Work Package 3 of SafetyNet deals with Safety Performance Indicators. They measure the operationa... more Work Package 3 of SafetyNet deals with Safety Performance Indicators. They measure the operational conditions of the road traffic system. Work Package 3 deals with seven topics: alcohol and drug use; speeds; protective systems; daytime running lights; vehicles; road; trauma management. This deliverable concerns the contribution of Work Package 3 to the first SafetyNet conference, which was held in Prague on May 10 and 11, 2006. Each topic prepared a poster with an overview of the state-of-play. In this document, these posters are assembled. Each topic has a preferred indicator, which can be used for measuring safety performance across countries. This indicator is accompanied by requirements that should be met by the data, in order to be able to calculate the indicator. For most tasks, values could be calculated for the indicators by using the available data. Data are not available for all countries and/or all topics.
To predict human pharmacokinetics (PK) such as the clearance and the plasma concentration profile... more To predict human pharmacokinetics (PK) such as the clearance and the plasma concentration profile of a new compound many animal-based methods have been used in the past. They are typically based on animal information of the compound of interest only (Mahmood 2005). This step translational is crucial in pharmaceutical development since it is used to estimate the human pharmacokinetics parameters
Upon maturation, primary neuronal cultures form an interconnected network based on neurite outgro... more Upon maturation, primary neuronal cultures form an interconnected network based on neurite outgrowth and synaptogenesis in which spontaneous electrical activity arises. Measurement of network activity allows quantification of neuronal health and maturation. A fluorescent indicator was used to monitor secondary calcium influxes after the occurrence of action potentials, allowing us to examine activity of hippocampal cultures via confocal live cell imaging. Subsequently, nuclear staining with DAPI allows accurate cell segmentation. To analyze the calcium recording in a robust, observer-independent manner, we implemented an automated image- and signal-processing algorithm and validated it against a visual, interactive procedure. Both methods yielded similar results on the emergence of synchronized activity and allowed robust quantitative measurement of acute and chronic modulation of drugs on network activity. Both the number of days in vitro (DIV) and neutralization of nerve growth factor (NGF) have a significant effect on synchronous burst frequency and correlation. Acute effects are demonstrated using 5-HT (serotonin) and ethylene glycol tetra-acetic acid. Automated analysis allowed measuring additional features, such as peak decay times and bursting frequency of individual neurons. Based on neuronal cell cultures in 96-well plates and accurate calcium recordings, the analysis method allows development of an integrated high-content screening assay. Because molecular biological techniques can be applied to assess the influence of genes on network activity, it is applicable for neurotoxicity or neurotrophics screening as well as development of in vitro disease models via, for example, pharmacologic manipulation or RNAi.
Maintainer Setia Pramana <[email protected]> Description The IsoGene Graphical User Inter... more Maintainer Setia Pramana <[email protected]> Description The IsoGene Graphical User Interface (IsoGene-GUI) is a user friendly inter-face of the IsoGene package which is aimed to identify for genes with a mono-tonic trend in the expression levels with respect to the increasing doses using several test statis-tics: global likelihood ratio test (E2), Bartholomew 1961, Barlow et al. 1972 and Robert-son et al. 1988), Williams (1971, 1972), Marcus (1976), the M (Hu et al. 2005) and the modi-fied M (Lin et al. 2007). The p-values of the global likelihood ratio test (E2) are obtained us-ing the excat distribution and permutation. The other four test statistics are obtained using per-mutation . Several p-values adjustment are provided: Bonfer-roni, Holm (1979), Hochberg (1988), and Sidak procedures for controlling the family-wise Type I error rate (FWER), and BH (Benjamini and Hochberg 1995) and BY (Ben-jamini and Yekutieli 2001) procedures are used for controlling the FDR. the infe...
Background: Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infect... more Background: Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infections, followed by lifelong nonpathogenic persistence. HPyV, and specifically JCPyV, are known to co-diverge with their host, implying a slow rate of viral evolution and a large timescale of virus/host co-existence. Recent bio-informatic reports showed a large level of peptide homology between JCPyV and the human proteome. In this study, the antibody response to PyV peptides is evaluated. Methods: The in-silico analysis of the HPyV proteome was followed by peptide microarray serology. A HPyV-peptide microarray containing 4,284 peptides was designed and covered 10 polyomavirus proteomes. Plasma samples from 49 healthy subjects were tested against these peptides. Results: In-silico analysis of all possible HPyV 5-mer amino acid sequences were compared to the human proteome, and 1,609 unique motifs are presented. Assuming a linear epitope being as small as a pentapeptide, on average 9.3% of the polyomavirus proteome is unique and could be recognized by the host as non-self. Small t Ag (stAg) contains a significantly higher percentage of unique pentapeptides. Experimental evidence for the presence of antibodies against HPyV 15-mer peptides in healthy subjects resulted in the following observations: i) antibody responses against stAg were significantly elevated, and against viral protein 2 (VP2) significantly reduced; and ii) there was a significant correlation between the increasing number of embedded unique HPyV penta-peptides and the increase in microarray fluorescent signal. Conclusion: The anti-peptide HPyV-antibodies in healthy subjects are preferably directed against the penta-peptide derived unique fraction of the viral proteome.
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