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  1. Article ; Online: SCelVis

    Benedikt Obermayer / Manuel Holtgrewe / Mikko Nieminen / Clemens Messerschmidt / Dieter Beule

    PeerJ, Vol 8, p e

    exploratory single cell data analysis on the desktop and in the cloud

    2020  Volume 8607

    Abstract: Background Single cell omics technologies present unique opportunities for biomedical and life sciences from lab to clinic, but the high dimensional nature of such data poses challenges for computational analysis and interpretation. Furthermore, FAIR ... ...

    Abstract Background Single cell omics technologies present unique opportunities for biomedical and life sciences from lab to clinic, but the high dimensional nature of such data poses challenges for computational analysis and interpretation. Furthermore, FAIR data management as well as data privacy and security become crucial when working with clinical data, especially in cross-institutional and translational settings. Existing solutions are either bound to the desktop of one researcher or come with dependencies on vendor-specific technology for cloud storage or user authentication. Results To facilitate analysis and interpretation of single-cell data by users without bioinformatics expertise, we present SCelVis, a flexible, interactive and user-friendly app for web-based visualization of pre-processed single-cell data. Users can survey multiple interactive visualizations of their single cell expression data and cell annotation, define cell groups by filtering or manual selection and perform differential gene expression, and download raw or processed data for further offline analysis. SCelVis can be run both on the desktop and cloud systems, accepts input from local and various remote sources using standard and open protocols, and allows for hosting data in the cloud and locally. We test and validate our visualization using publicly available scRNA-seq data. Methods SCelVis is implemented in Python using Dash by Plotly. It is available as a standalone application as a Python package, via Conda/Bioconda and as a Docker image. All components are available as open source under the permissive MIT license and are based on open standards and interfaces, enabling further development and integration with third party pipelines and analysis components. The GitHub repository is https://github.com/bihealth/scelvis.
    Keywords Single cell ; Visualization ; tSNE ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 004
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Exploring the miRNA regulatory network using evolutionary correlations.

    Benedikt Obermayer / Erel Levine

    PLoS Computational Biology, Vol 10, Iss 10, p e

    2014  Volume 1003860

    Abstract: Post-transcriptional regulation by miRNAs is a widespread and highly conserved phenomenon in metazoans, with several hundreds to thousands of conserved binding sites for each miRNA, and up to two thirds of all genes under miRNA regulation. At the same ... ...

    Abstract Post-transcriptional regulation by miRNAs is a widespread and highly conserved phenomenon in metazoans, with several hundreds to thousands of conserved binding sites for each miRNA, and up to two thirds of all genes under miRNA regulation. At the same time, the effect of miRNA regulation on mRNA and protein levels is usually quite modest and associated phenotypes are often weak or subtle. This has given rise to the notion that the highly interconnected miRNA regulatory network exerts its function less through any individual link and more via collective effects that lead to a functional interdependence of network links. We present a Bayesian framework to quantify conservation of miRNA target sites using vertebrate whole-genome alignments. The increased statistical power of our phylogenetic model allows detection of evolutionary correlation in the conservation patterns of site pairs. Such correlations could result from collective functions in the regulatory network. For instance, co-conservation of target site pairs supports a selective benefit of combinatorial regulation by multiple miRNAs. We find that some miRNA families are under pronounced co-targeting constraints, indicating a high connectivity in the regulatory network, while others appear to function in a more isolated way. By analyzing coordinated targeting of different curated gene sets, we observe distinct evolutionary signatures for protein complexes and signaling pathways that could reflect differences in control strategies. Our method is easily scalable to analyze upcoming larger data sets, and readily adaptable to detect high-level selective constraints between other genomic loci. We thus provide a proof-of-principle method to understand regulatory networks from an evolutionary perspective.
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2014-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Inverse Ising inference with correlated samples

    Benedikt Obermayer / Erel Levine

    New Journal of Physics, Vol 16, Iss 12, p

    2014  Volume 123017

    Abstract: Correlations between two variables of a high-dimensional system can be indicative of an underlying interaction, but can also result from indirect effects. Inverse Ising inference is a method to distinguish one from the other. Essentially, the parameters ... ...

    Abstract Correlations between two variables of a high-dimensional system can be indicative of an underlying interaction, but can also result from indirect effects. Inverse Ising inference is a method to distinguish one from the other. Essentially, the parameters of the least constrained statistical model are learned from the observed correlations such that direct interactions can be separated from indirect correlations. Among many other applications, this approach has been helpful for protein structure prediction, because residues which interact in the 3D structure often show correlated substitutions in a multiple sequence alignment. In this context, samples used for inference are not independent but share an evolutionary history on a phylogenetic tree. Here, we discuss the effects of correlations between samples on global inference. Such correlations could arise due to phylogeny but also via other slow dynamical processes. We present a simple analytical model to address the resulting inference biases, and develop an exact method accounting for background correlations in alignment data by combining phylogenetic modeling with an adaptive cluster expansion algorithm. We find that popular reweighting schemes are only marginally effective at removing phylogenetic bias, suggest a rescaling strategy that yields better results, and provide evidence that our conclusions carry over to the frequently used mean-field approach to the inverse Ising problem.
    Keywords inverse problems ; statistical sequence analysis ; phylogenetic inference ; Science ; Q ; Physics ; QC1-999
    Subject code 612
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher IOP Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Correction

    Morris Baumgardt / Maren Hülsemann / Anna Löwa / Diana Fatykhova / Karen Hoffmann / Mirjana Kessler / Maren Mieth / Katharina Hellwig / Doris Frey / Alina Langenhagen / Anne Voss / Benedikt Obermayer / Emanuel Wyler / Simon Dökel / Achim D Gruber / Ulf Tölch / Stefan Hippenstiel / Andreas C Hocke / Katja Hönzke

    PLoS ONE, Vol 18, Iss 11, p e

    State-of-the-art analytical methods of viral infections in human lung organoids.

    2023  Volume 0294216

    Abstract: This corrects the article DOI:10.1371/journal.pone.0276115.]. ...

    Abstract [This corrects the article DOI:10.1371/journal.pone.0276115.].
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex

    Sarah M. Kedziora / Benedikt Obermayer / Meryam Sugulle / Florian Herse / Kristin Kräker / Nadine Haase / Immaculate M. Langmia / Dominik N. Müller / Anne Cathrine Staff / Dieter Beule / Ralf Dechend

    International Journal of Molecular Sciences, Vol 23, Iss 15388, p

    2022  Volume 15388

    Abstract: The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A ... ...

    Abstract The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A diabetic state affects maternal and fetal health and may lead to functional alterations of placental metabolism, inflammation, hypoxia, and weight, amplifying the fetal stress. The placental molecular adaptations to the diabetic environment and the adaptive spatio–temporal consequences to elevated glucose or insulin are largely unknown (2). We aimed to identify gene expression signatures related to the diabetic placental pathology of placentas from women with diabetes mellitus. Human placenta samples ( n = 77) consisting of healthy controls, women with either gestational diabetes mellitus (GDM), type 1 or type 2 diabetes, and women with GDM, type 1 or type 2 diabetes and superimposed PE were collected. Interestingly, gene expression differences quantified by total RNA sequencing were mainly driven by fetal sex rather than clinical diagnosis. Association of the principal components with a full set of clinical patient data identified fetal sex as the single main explanatory variable. Accordingly, placentas complicated by type 1 and type 2 diabetes showed only few differentially expressed genes, while possible effects of GDM and diabetic pregnancy complicated by PE were not identifiable in this cohort. We conclude that fetal sex has a prominent effect on the placental transcriptome, dominating and confounding gene expression signatures resulting from diabetes mellitus in settings of well-controlled diabetic disease. Our results support the notion of placenta as a sexual dimorphic organ.
    Keywords diabetes mellitus ; human ; placenta ; pregnancy ; RNA sequencing ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Transcriptomic comparison of primary human lung cells with lung tissue samples and the human A549 lung cell line highlights cell type specific responses during infections with influenza A virus

    Wilhelm Bertrams / Katja Hönzke / Benedikt Obermayer / Mario Tönnies / Torsten T. Bauer / Paul Schneider / Jens Neudecker / Jens C. Rückert / Thorsten Stiewe / Andrea Nist / Stephan Eggeling / Norbert Suttorp / Thorsten Wolff / Stefan Hippenstiel / Bernd Schmeck / Andreas C. Hocke

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 11

    Abstract: Abstract Influenza A virus (IAV) causes pandemics and annual epidemics of severe respiratory infections. A better understanding of the molecular regulation in tissue and cells upon IAV infection is needed to thoroughly understand pathogenesis. We ... ...

    Abstract Abstract Influenza A virus (IAV) causes pandemics and annual epidemics of severe respiratory infections. A better understanding of the molecular regulation in tissue and cells upon IAV infection is needed to thoroughly understand pathogenesis. We analyzed IAV replication and gene expression induced by IAV strain H3N2 Panama in isolated primary human alveolar epithelial type II cells (AECIIs), the permanent A549 adenocarcinoma cell line, alveolar macrophages (AMs) and explanted human lung tissue by bulk RNA sequencing. Primary AECII exhibit in comparison to AM a broad set of strongly induced genes related to RIG-I and interferon (IFN) signaling. The response of AECII was partly mirrored in A549 cells. In human lung tissue, we observed induction of genes unlike in isolated cells. Viral RNA was used to correlate host cell gene expression changes with viral burden. While relative induction of key genes was similar, gene abundance was highest in AECII cells and AM, while weaker in the human lung (due to less IAV replication) and A549 cells (pointing to their limited suitability as a model). Correlation of host gene induction with viral burden allows a better understanding of the cell-type specific induction of pathways and a possible role of cellular crosstalk requiring intact tissue.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Tracing tumorigenesis in a solid tumor model at single-cell resolution

    Samantha D. Praktiknjo / Benedikt Obermayer / Qionghua Zhu / Liang Fang / Haiyue Liu / Hazel Quinn / Marlon Stoeckius / Christine Kocks / Walter Birchmeier / Nikolaus Rajewsky

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Understanding tumour development at a granular level is a challenge in solid tumours. Here, the authors provide a cell atlas across tumour development in a genetic model of salivary gland squamous cell carcinoma using single-cell transcriptome and ... ...

    Abstract Understanding tumour development at a granular level is a challenge in solid tumours. Here, the authors provide a cell atlas across tumour development in a genetic model of salivary gland squamous cell carcinoma using single-cell transcriptome and epitope profiling.
    Keywords Science ; Q
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Tracing tumorigenesis in a solid tumor model at single-cell resolution

    Samantha D. Praktiknjo / Benedikt Obermayer / Qionghua Zhu / Liang Fang / Haiyue Liu / Hazel Quinn / Marlon Stoeckius / Christine Kocks / Walter Birchmeier / Nikolaus Rajewsky

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Understanding tumour development at a granular level is a challenge in solid tumours. Here, the authors provide a cell atlas across tumour development in a genetic model of salivary gland squamous cell carcinoma using single-cell transcriptome and ... ...

    Abstract Understanding tumour development at a granular level is a challenge in solid tumours. Here, the authors provide a cell atlas across tumour development in a genetic model of salivary gland squamous cell carcinoma using single-cell transcriptome and epitope profiling.
    Keywords Science ; Q
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19

    Ronja Mothes / Anna Pascual-Reguant / Ralf Koehler / Juliane Liebeskind / Alina Liebheit / Sandy Bauherr / Lars Philipsen / Carsten Dittmayer / Michael Laue / Regina von Manitius / Sefer Elezkurtaj / Pawel Durek / Frederik Heinrich / Gitta A. Heinz / Gabriela M. Guerra / Benedikt Obermayer / Jenny Meinhardt / Jana Ihlow / Josefine Radke /
    Frank L. Heppner / Philipp Enghard / Helena Stockmann / Tom Aschman / Julia Schneider / Victor M. Corman / Leif E. Sander / Mir-Farzin Mashreghi / Thomas Conrad / Andreas C. Hocke / Raluca A. Niesner / Helena Radbruch / Anja E. Hauser

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 16

    Abstract: Infection with SARS-CoV-2 has been linked with substantive inflammation, lung pathology and development of COVID-19. Here the authors spatially associate CCL18 and CCL21 in distinct tissue niches with lung pathology of severe COVID-19. ...

    Abstract Infection with SARS-CoV-2 has been linked with substantive inflammation, lung pathology and development of COVID-19. Here the authors spatially associate CCL18 and CCL21 in distinct tissue niches with lung pathology of severe COVID-19.
    Keywords Science ; Q
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19

    Geraldine Nouailles / Emanuel Wyler / Peter Pennitz / Dylan Postmus / Daria Vladimirova / Julia Kazmierski / Fabian Pott / Kristina Dietert / Michael Muelleder / Vadim Farztdinov / Benedikt Obermayer / Sandra-Maria Wienhold / Sandro Andreotti / Thomas Hoefler / Birgit Sawitzki / Christian Drosten / Leif E. Sander / Norbert Suttorp / Markus Ralser /
    Dieter Beule / Achim D. Gruber / Christine Goffinet / Markus Landthaler / Jakob Trimpert / Martin Witzenrath

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 18

    Abstract: The immune response is key in determining disease severity of COVID19. Here Nouailles et al., apply bulk proteomics and scRNA-Seq of lung and blood samples of SARS-CoV-2 infected Syrian hamsters and provide a temporal atlas of the systemic and pulmonary ... ...

    Abstract The immune response is key in determining disease severity of COVID19. Here Nouailles et al., apply bulk proteomics and scRNA-Seq of lung and blood samples of SARS-CoV-2 infected Syrian hamsters and provide a temporal atlas of the systemic and pulmonary cellular responses.
    Keywords Science ; Q
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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