i2dash: Creation of Flexible, Interactive, and Web-based Dashboards for Visualization of Omics Data

Data visualization and interactive data exploration are important aspects of illustrating complex concepts and results from analyses of omics data. A suitable visualization has to be intuitive and accessible. Web-based dashboards have become popular tools for the arrangement, consolidation, and display of such visualizations. However, the combination of automated data processing pipelines handling omics data and dynamically generated, interactive dashboards is poorly solved. Here, we present i2dash, an R package intended to encapsulate functionality for the programmatic creation of customized dashboards. It supports interactive and responsive (linked) visualizations across a set of predefined graphical layouts. i2dash addresses the needs of data analysts/software developers for a tool that is compatible and attachable to any R-based analysis pipeline, thereby fostering the separation of data visualization on one hand and data analysis tasks on the other hand. In addition, the generic design of i2dash enables the development of modular extensions for specific needs. As a proof of principle, we provide an extension of i2dash optimized for single-cell RNA sequencing analysis, supporting the creation of dashboards for the visualization needs of such experiments. Equipped with these features, i2dash is suitable for extensive use in large-scale sequencing/bioinformatics facilities. Along this line, we provide i2dash as a containerized solution, enabling a straightforward large-scale deployment and sharing of dashboards using cloud services. i2dash is freely available via the R package archive CRAN (https://CRAN.R-project.org/package=i2dash)

PISA 2015 Skalenhandbuch

Dieses Skalenhandbuch für das Programme for International Student Assessment (PISA) 2015 umfasst die Dokumentation aller Instrumente, die in der Studie im Jahre 2015 in Deutschland eingesetzt wurden. Neben den Fragen – den sogenannten Items – des Schülerfragebogens, des Elternfragebogens, des Lehrerfragebogens sowie des Schulleiterfragebogens werden die mittleren (internationalen und nationalen) Lösungshäufigkeiten der verwendeten Testaufgaben für die Domänen Naturwissenschaften, Lesen und Mathematik aufgelistet. In der Erhebung 2015 bildete die Domäne Naturwissenschaften zum zweiten Mal die Hauptdomäne. Es werden sowohl die internationalen Fragen als auch Fragen abgebildet, welche nur in Deutschland erhoben worden sind

Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance

International audienceNon-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don’t have a direct pathway producing α-GalCer, which, however, can be produced by bacteria. We searched the literature for bacteria strains that are able to produce α-GalCer and used available sequencing data to analyze their presence in human tumor tissues and their association with survival. The modulatory effect of antibiotics on the concentration of α-GalCer was analyzed in mice. The human gut bacteria Bacteroides fragilis, Bacteroides vulgatus, and Prevotella copri produce α-GalCer structures that are able to activate iNKT cells. In mice, α-GalCer was depleted upon treatment with vancomycin. The three species were detected in colon adenocarcinoma (COAD) and rectum adenocarcinoma tissues, and Prevotella copri was also detected in bone tumors and glioblastoma tissues. Bacteroides vulgatus in COAD tissues correlated with better survival. In conclusion, α-GalCer-producing bacteria are part of the human gut microbiome and can infiltrate tumor tissues. These results suggest a new mechanism of interaction between bacteria and immune cells: α-GalCer produced by bacteria may activate non-conventional T cells in tumor tissues, where they can exert a direct or indirect anti-tumor activity

PISA 2012 Skalenhandbuch. Dokumentation der Erhebungsinstrumente

Das Skalenhandbuch für das Programme for International Student Assessment (PISA) 2012 umfasst die Dokumentation aller Instrumente, die in der Studie im Jahre 2012 in Deutschland eingesetzt wurden. In der Erhebung 2012 bildete Mathematik zum zweiten Mal die Hauptdomäne. Neben den Fragen – den sogenannten Items – des Schüler-, Eltern-, Lehrer- sowie des Schulleiterfragebogens werden die mittleren Lösungshäufigkeiten der verwendeten Testaufgaben für die Domänen Mathematik, Lesen und Naturwissenschaften aufgelistet. Des Weiteren werden Schülerangaben zu ihrer subjektiven Anstrengungsbereitschaft bei der Testbearbeitung veröffentlicht. Es werden sowohl die internationalen Fragen als auch solche Fragen abgebildet, die nur in Deutschland erhoben wurden. (DIPF/Orig.

PISA 2012 Skalenhandbuch

Das Skalenhandbuch für das Programme for International Student Assessment (PISA) 2012 umfasst die Dokumentation aller Instrumente, die in der Studie im Jahre 2012 in Deutschland eingesetzt wurden. In der Erhebung 2012 bildete Mathematik zum zweiten Mal die Hauptdomäne. Neben den Fragen – den sogenannten Items – des Schüler-, Eltern-, Lehrer- sowie des Schulleiterfragebogens werden die mittleren Lösungshäufigkeiten der verwendeten Testaufgaben für die Domänen Mathematik, Lesen und Naturwissenschaften aufgelistet. Des Weiteren werden Schülerangaben zu ihrer subjektiven Anstrengungsbereitschaft bei der Testbearbeitung veröffentlicht. Es werden sowohl die internationalen Fragen als auch solche Fragen abgebildet, die nur in Deutschland erhoben wurden

cbpManager: a web application to streamline the integration of clinical and genomic data in cBioPortal to support the Molecular Tumor Board

Background!#!Extensive sequencing of tumor tissues has greatly improved our understanding of cancer biology over the past years. The integration of genomic and clinical data is increasingly used to select personalized therapies in dedicated tumor boards (Molecular Tumor Boards) or to identify patients for basket studies. Genomic alterations and clinical information can be stored, integrated and visualized in the open-access resource cBioPortal for Cancer Genomics. cBioPortal can be run as a local instance enabling storage and analysis of patient data in single institutions, in the respect of data privacy. However, uploading clinical input data and genetic aberrations requires the elaboration of multiple data files and specific data formats, which makes it difficult to integrate this system into clinical practice. To solve this problem, we developed cbpManager.!##!Results!#!cbpManager is an R package providing a web-based interactive graphical user interface intended to facilitate the maintenance of mutations data and clinical data, including patient and sample information, as well as timeline data. cbpManager enables a large spectrum of researchers and physicians, regardless of their informatics skills to intuitively create data files ready for upload in cBioPortal for Cancer Genomics on a daily basis or in batch. Due to its modular structure based on R Shiny, further data formats such as copy number and fusion data can be covered in future versions. Further, we provide cbpManager as a containerized solution, enabling a straightforward large-scale deployment in clinical systems and secure access in combination with ShinyProxy. cbpManager is freely available via the Bioconductor project at https://bioconductor.org/packages/cbpManager/ under the AGPL-3 license. It is already used at six University Hospitals in Germany (Mainz, Gießen, Lübeck, Halle, Freiburg, and Marburg).!##!Conclusion!#!In summary, our package cbpManager is currently a unique software solution in the workflow with cBioPortal for Cancer Genomics, to assist the user in the interactive generation and management of study files suited for the later upload in cBioPortal

Analysis of RBP expression and binding sites identifies PTBP1 as a regulator of CD19 expression in B-ALL

ABSTRACTDespite massive improvements in the treatment of B-ALL through CART-19 immunotherapy, a large number of patients suffer a relapse due to loss of the targeted epitope. Mutations in the CD19 locus and aberrant splicing events are known to account for the absence of surface antigen. However, early molecular determinants suggesting therapy resistance as well as the time point when first signs of epitope loss appear to be detectable are not enlightened so far. By deep sequencing of the CD19 locus, we identified a blast-specific 2-nucleotide deletion in intron 2 that exists in 35% of B-ALL samples at initial diagnosis. This deletion overlaps with the binding site of RNA binding proteins (RBPs) including PTBP1 and might thereby affect CD19 splicing. Moreover, we could identify a number of other RBPs that are predicted to bind to the CD19 locus being deregulated in leukemic blasts, including NONO. Their expression is highly heterogeneous across B-ALL molecular subtypes as shown by analyzing 706 B-ALL samples accessed via the St. Jude Cloud. Mechanistically, we show that downregulation of PTBP1, but not of NONO, in 697 cells reduces CD19 total protein by increasing intron 2 retention. Isoform analysis in patient samples revealed that blasts, at diagnosis, express increased amounts of CD19 intron 2 retention compared to normal B cells. Our data suggest that loss of RBP functionality by mutations altering their binding motifs or by deregulated expression might harbor the potential for the disease-associated accumulation of therapy-resistant CD19 isoforms

Glucosylceramide Synthase Inhibitors Induce Ceramide Accumulation and Sensitize H3K27 Mutant Diffuse Midline Glioma to Irradiation

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2 in a concentration and time-dependent manner and increased the expression of ceramide, ceramide 1-phosphate, sphingosine, and sphingomyelin but not of sphingosine 1-phosphate. Miglustat significantly increased the efficacy of irradiation. Treatment with miglustat according to dose recommendations for patients with Niemann–Pick disease was well tolerated with manageable toxicities. One patient showed a mixed response. In ependymoma, a high concentration of GD2 was found only in the presence of the loss of H3.3K27 trimethylation. In conclusion, treatment with miglustat and, in general, targeting GSL metabolism may offer a new therapeutic opportunity and can be administered in close proximity to radiation therapy. Alterations in H3K27 could be useful to identify patients with a deregulated GSL metabolism