Biology subjects

Preussner, J.

Publications and source records attributed to Preussner, J..

7 recordsLinked to original sources

bioRxiv2020

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

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 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 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 data analysts to generate 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 single-cell sequencing 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.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioinformatics↗

bioRxiv2020

multicrispr: fast gRNA designer enables prime editing and parallel targeting of thousands of targets

Targeting the coding genome to introduce single nucleotide deletions/insertions via Crispr/Cas9 technology has become a standard procedure in recent years. It has quickly spawned a multitude of methods such as Prime Editing, Crispr/Cas9 assisted APEX proximity labeling of proteins, or homology directed repair (HDR), for which supporting bioinformatic tools are, however, lagging behind. New applications often require specific guide-RNA (gRNA) design functionality, and a generic gRNA design tool is critically missing. Here we review gRNA designer software and introduce multicrispr, an R based tool intended to design individual gRNAs as well as gRNA libraries targeting many genomic loci in parallel. The package is easy to use, detects, scores and filters gRNAs on both efficiency and specificity, visualizes and aggregates results per target or Crispr/Cas9 sequence, and finally returns both genomic ranges as well as sequences of preferred, off target-free gRNAs. In order to be generic, multicrispr defines and implements a genomic arithmetics framework as a basis for facile adaptation to techniques yet to arise. Its performance and new gRNA design concepts such as target set specific filtering for gRNA libraries render multicrispr the tool of choice when dealing with screening-like approaches.

bioinformatics↗

bioRxiv2019

Beyond accessibility: ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation

While footprinting analysis of ATAC-seq data can theoretically enable investigation of transcription factor (TF) binding, the lack of a computational tool able to conduct different levels of footprinting analysis has so-far hindered the widespread application of this method. Here we present TOBIAS, a comprehensive, accurate, and fast footprinting framework enabling genome-wide investigation of TF binding dynamics for hundreds of TFs simultaneously. As a proof-of-concept, we illustrate how TOBIAS can unveil complex TF dynamics during zygotic genome activation (ZGA) in both humans and mice, and explore how zygotic Dux activates cascades of TFs, binds to repeat elements and induces expression of novel genetic elements. TOBIAS is freely available at: https://github.com/loosolab/TOBIAS.

bioinformatics↗

bioRxiv2018

Myh10 deficiency leads to defective extracellular matrix remodeling and pulmonary disease

Impaired alveolar formation and maintenance are features of many pulmonary diseases that are associated with significant morbidity and mortality. In a forward genetic screen for modulators of mouse lung development, we identified the non-muscle myosin II heavy chain gene, Myh10. Myh10 mutant pups exhibit cyanosis and respiratory distress, and die shortly after birth from differentiation defects in alveolar epithelium and mesenchyme. From omics analyses and follow up studies, we find decreased Thrombospondin expression accompanied with increased matrix metalloproteinase activity in both mutant lungs and cultured mutant fibroblasts, as well as disrupted extracellular matrix (ECM) remodeling. Loss of Myh10 specifically in mesenchymal cells results in ECM deposition defects and alveolar simplification. Notably, MYH10 expression is down-regulated in the lung of emphysema patients. Altogether, our findings reveal critical roles for Myh10 in alveologenesis at least in part via the regulation of ECM remodeling, which may contribute to the pathogenesis of emphysema.

developmental biology↗

bioRxiv2018

The potassium channel KCNJ13 is essential for smooth muscle cytoskeletal organization during mouse tracheal tubulogenesis

Tubulogenesis is essential for the formation and function of internal organs. One such organ is the trachea, which allows gas exchange between the external environment and the lungs. However, the cellular and molecular mechanisms underlying tracheal tube development remain poorly understood. Here, we show that the potassium channel KCNJ13 is a critical modulator of tracheal tubulogenesis. We identify Kcnj13 in an ethylnitrosourea forward genetic screen for regulators of mouse respiratory organ development. Kcnj13 mutants exhibit a shorter trachea as well as defective smooth muscle (SM) cell alignment and polarity. KCNJ13 is essential to maintain ion homeostasis in tracheal SM cells, which is required for actin polymerization. This process appears to be mediated, at least in part, through activation of the actin regulator AKT, as pharmacological increase of AKT phosphorylation ameliorates the Kcnj13 mutant trachea phenotypes. These results provide insights into the role of ion homeostasis in cytoskeletal organization during tubulogenesis.

developmental biology↗

bioRxiv2018

UROPA GUI: A web platform for genomic region annotation

The annotation of genomic ranges such as peaks resulting from ChIP-seq/ATAC-seq or other techniques represents a fundamental task of bioinformatics analysis with considerable impact on many downstream analyses. In our previous work, we introduced the Universal Robust Peak Annotator (UROPA), a flexible command line based tool which improves upon the functionality of existing annotation software. In order to reduce the complexity for biologists and clinicians, we have implemented an intuitive web-based graphical user interface (GUI) and fully functional service platform for UROPA. This extension will empower all users to generate annotations for regions of interest interactively.\n\nAvailability and ImplementationThe open source UROPA GUI server was implemented in R Shiny and Python and is available from http://loosolab.mpi-bn.mpg.de. The source code of our App can be downloaded at https://github.molgen.mpg.de/loosolab/UROPA_GUI under the MIT license.

bioinformatics↗

bioRxiv2017

Single-cell transcriptional regulations and accessible chromatin landscape of cell fate decisions in early heart development

Formation and segregation of the cell lineages forming the vertebrate heart have been studied extensively by genetic cell tracing techniques and by analysis of single marker gene expression both in embryos and differentiating ES cells. However, the underlying gene regulatory networks driving cell fate transitions during early cardiogenesis is only partially understood, in part due to limited cell numbers and substantial cellular heterogeneity within the early embryo. Here, we comprehensively characterized cardiac progenitor cells (CPC) marked by Nkx2-5 and Isl1 expression from embryonic days E7.5 to E9.5 using single-cell RNA sequencing. By leveraging on cell-to-cell heterogeneity, we identified different previously unknown cardiac sub-populations. Reconstruction of the developmental trajectory revealed that Isl1+ CPC represent a transitional cell population maintaining a prolonged multipotent state, whereas extended expression of Nkx-2.5 commits CPC to a unidirectional cardiomyocyte fate. Correlation-based analysis of cells in the unstable multipotent state uncovered underlying gene regulatory networks associated with differentiation. Furthermore, we show that CPC fate transitions are associated with distinct open chromatin states, which critically depend on Isl1 for accessibility of enhancers. In contrast, forced expression of Nkx2-5 eliminated multipotency of Isl1+ cells and established a unidirectional cardiomyocyte fate. Our data provides a transcriptional map for early cardiogenic events at single-cell resolution and establishes a general model of transcriptional and epigenetic regulations during cardiac progenitor cell fate decisions.

developmental biology↗