TY - JOUR A1 - Hoang, Yen A1 - Gryzik, Stefanie A1 - Hoppe, Ines A1 - Rybak, Alexander A1 - Schädlich, Martin A1 - Kadner, Isabelle A1 - Walther, Dirk A1 - Vera, Julio A1 - Radbruch, Andreas A1 - Groth, Detlef A1 - Baumgart, Sabine A1 - Baumgrass, Ria T1 - PRI: Re-analysis of a public mass cytometry dataset reveals patterns of effective tumor treatments JF - Frontiers in immunology N2 - Recently, mass cytometry has enabled quantification of up to 50 parameters for millions of cells per sample. It remains a challenge to analyze such high-dimensional data to exploit the richness of the inherent information, even though many valuable new analysis tools have already been developed. We propose a novel algorithm "pattern recognition of immune cells (PRI)" to tackle these high-dimensional protein combinations in the data. PRI is a tool for the analysis and visualization of cytometry data based on a three or more-parametric binning approach, feature engineering of bin properties of multivariate cell data, and a pseudo-multiparametric visualization. Using a publicly available mass cytometry dataset, we proved that reproducible feature engineering and intuitive understanding of the generated bin plots are helpful hallmarks for re-analysis with PRI. In the CD4(+)T cell population analyzed, PRI revealed two bin-plot patterns (CD90/CD44/CD86 and CD90/CD44/CD27) and 20 bin plot features for threshold-independent classification of mice concerning ineffective and effective tumor treatment. In addition, PRI mapped cell subsets regarding co-expression of the proliferation marker Ki67 with two major transcription factors and further delineated a specific Th1 cell subset. All these results demonstrate the added insights that can be obtained using the non-cluster-based tool PRI for re-analyses of high-dimensional cytometric data. KW - multi-parametric analysis KW - re-analysis KW - combinatorial protein KW - expression KW - high-dimensional cytometry data KW - mass cytometry data KW - pattern perception Y1 - 2022 U6 - https://doi.org/10.3389/fimmu.2022.849329 SN - 1664-3224 VL - 13 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Gryzik, Stefanie A1 - Hoang, Yen A1 - Lischke, Timo A1 - Mohr, Elodie A1 - Venzke, Melanie A1 - Kadner, Isabelle A1 - Pötzsch, Josephine A1 - Groth, Detlef A1 - Radbruch, Andreas A1 - Hutloff, Andreas A1 - Baumgrass, Ria T1 - Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception JF - eLife N2 - Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)". PRI uncovered a subpopulation of IL-21(+) IFN-gamma(high) PD-1(low) CD40L(high) CXCR5(-) Bcl-6(-) T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-alpha and IL-2, and provide B cell help for IgG production in an IL-21 and CD40L dependent manner. This super-functional T cell subset might be a superior driver of autoimmune processes due to a polyfunctional and high cytokine expression combined with Tfh-like properties. Y1 - 2020 U6 - https://doi.org/10.7554/eLife.53226 SN - 2050-084X VL - 9 PB - eLife Sciences Publications CY - Cambridge ER - TY - THES A1 - Baumgrass, Ria T1 - Die Rolle von Calcineurin bei der antigenspezifischen Aktivierung und Differenzierung von T-Helfer-Zellen Y1 - 2007 ER - TY - THES A1 - Baumgrass, Ria T1 - Die Rolle von Calcineurin bei der antigenspezifischen Aktivierung und Differenzierung von T-Helfer-Zellen Y1 - 2007 CY - Potsdam ER - TY - JOUR A1 - Jargosch, M. A1 - Kroeger, S. A1 - Gralinska, E. A1 - Klotz, Ulrike A1 - Fang, Z. A1 - Chen, W. A1 - Leser, U. A1 - Selbig, Joachim A1 - Groth, Detlef A1 - Baumgrass, Ria T1 - Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions JF - Genetics and molecular research N2 - Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hifla) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes. KW - Data integration KW - Th2 cells KW - Gene regulatory network KW - STAT6 KW - Transcription factors Y1 - 2016 U6 - https://doi.org/10.4238/gmr.15028493 SN - 1676-5680 VL - 15 PB - FUNPEC CY - Ribeirao Preto ER - TY - JOUR A1 - Kobel-Höller, Konstanze A1 - Gley, Kevin A1 - Jochinke, Janina A1 - Heider, Kristina A1 - Fritsch, Verena Nadin A1 - Ha Viet Duc Nguyen, A1 - Lischke, Timo A1 - Radek, Renate A1 - Baumgrass, Ria A1 - Mutzel, Rupert A1 - Thewes, Sascha T1 - Calcineurin Silencing in Dictyostelium discoideum Leads to Cellular Alterations Affecting Mitochondria, Gene Expression, and Oxidative Stress Response JF - Protist N2 - Calcineurin is involved in development and cell differentiation of the social amoeba Dictyostelium discoideum. However, since knockouts of the calcineurin-encoding genes are not possible in D. discoideum it is assumed that the phosphatase also plays a crucial role during vegetative growth of the amoebae. Therefore, we investigated the role of calcineurin during vegetative growth in D. discoideum. RNAi-silenced calcineurin mutants showed cellular alterations with an abnormal morphology of mitochondria and had increased content of mitochondrial DNA (mtDNA). In contrast, mitochondria showed no substantial functional impairment. Calcineurin-silencing led to altered expression of calcium-regulated genes as well as mitochondrially-encoded genes. Furthermore, genes related to oxidative stress were higher expressed in the mutants, which correlated to an increased resistance towards reactive oxygen species (ROS). Most of the changes observed during vegetative growth were not seen after starvation of the calcineurin mutants. We show that impairment of calcineurin led to many subtle, but in the sum crucial cellular alterations in vegetative D. discoideum cells. As these alterations were not observed after starvation we propose a dual role for calcineurin during growth and development. Our results imply that calcineurin is one player in the mutual interplay between mitochondria and ROS during vegetative growth. KW - mtDNA KW - mitochondrial remodelling KW - calcium KW - oxidative stress KW - phototaxis Y1 - 2018 U6 - https://doi.org/10.1016/j.protis.2018.04.004 SN - 1434-4610 VL - 169 IS - 4 SP - 584 EP - 602 PB - Elsevier GMBH CY - München ER -