Biology subjects

Schlüter, H.

Publications and source records attributed to Schlüter, H..

5 recordsLinked to original sources

bioRxiv2025

OmixLitMiner 2: Guided Literature Mining Tools for Automated Categorization of Marker Candidates in Omics Studies

Omics analyses are crucial for understanding molecular mechanisms in biological research. The vast quantity of detected biomolecules presents a significant challenge in identifying potential biomarkers. Traditional methods rely heavily on labor-intensive literature mining to extract meaningful insights from long lists of regulated candidates. To address this, we developed OmixLitMiner 2 to improve the efficiency of omics data interpretation, increase the speed for the validation of results and accelerate further evaluation based on the selection of marker candidates for subsequent experiments. The updated tool utilizes UniProt for synonym and protein name retrieval and employs the PubMed database as well as PubTator 3.0 for mining abstracts and full texts of available biomedical literature. It allows for advanced keyword-based searches and provides classification of proteins or genes with respect to their awareness level in relationship to scientific questions. OmixLitMiner 2 offers improved functionality over the previous version and comes with a user-friendly Google Colab interface. In comparison to the previous version OmixLitMiner 2 improves the retrieval and classification of relevant publications. The tool significantly reduces the time required for manual searches, as demonstrated in a case study involving proteomic data from spatially resolved mouse brain cortex layers. Statement of SignificanceWe developed OmixLitMiner 2 to determine, for a given set of marker candidates, the extent to which they have been described in the literature. The tool is easy-to-use and can quickly generate a categorized list of references obtained by automated literature searches for protein and gene names and involving keywords related to a specific scientific question. The categorization provides a ranking of how well-studied the genes or proteins: Candidates of category 1 are well-known regarding the scientific question; Candidates of category 2 have been mentioned in a publication associated with the specific scientific question; Candidates of category 3 have never been described to be associated with the specific scientific question; Candidates of category 4 are not yet known proteins and are not associated with a gene name. This classification can aid in the decision, which protein or gene candidates to choose for follow-up experiments.

bioinformatics↗

bioRxiv2023

Assay for characterizing adsorption-properties of surfaces (APS) sample preparation prior to quantitative omics

Analytes during their journey from their natural sources to their identification and quantification are prone to adsorption to surfaces before they enter an analytical instrument, causing false quantities. This problem is especially severe in diverse omics. Here, thousands of analytes with a broad range of chemical properties and thus different affinities to surfaces are quantified within a single analytical run. For quantifying adsorption effects caused by surfaces of sample handling tools, an assay was developed, applying LC-MS/MS-based differential bottom-up proteomics and as probe a reference mixture of thousands of tryptic peptides, covering a broad range of chemical properties. The assay was tested by investigating the adsorption properties of several vials composed of polypropylene, including low-protein-binding polypropylene vials, borosilicate glass vials and low-retention glass vials. In total 3531 different peptides were identified and quantified across all samples and therefore used as probes. A significant number of hydrophobic peptides adsorbed on polypropylene vials. In contrast, only very few peptides adsorbed to low-protein-binding polypropylene vials. The highest number of peptides adsorbed to glass vials, driven by electrostatic as well as hydrophobic interactions. Calculation of the impact of the adsorption of peptides on differential quantitative proteomics showed significant false results. In summary, the new assay is suitable to characterize adsorption properties of surfaces getting into contact with analytes during sample preparation, thereby giving the opportunity to find parameters for minimizing false quantities. Insert Table of Contents artwork here O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/551632v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@bafb12org.highwire.dtl.DTLVardef@1b98219org.highwire.dtl.DTLVardef@c3b45org.highwire.dtl.DTLVardef@1074180_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

Reducing microtubule detyrosination improves heart function in HCM mice and human iPSC-engineered heart tissues

RationaleHypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder caused by sarcomeric gene variants and associated with left ventricular (LV) hypertrophy and diastolic dysfunction. The role of the microtubule network has recently gained interest with the findings that -tubulin detyrosination (dTyr-tub) is markedly elevated in heart failure. Acute reduction of dTyr-tub by inhibition of the detyrosinase (VASH/SVBP complex) or activation of the tyrosinase (tubulin tyrosine ligase, TTL) markedly improved contractility and reduced stiffness in human failing cardiomyocytes, and thus poses a new perspective for HCM treatment. ObjectiveIn this study, we tested the impact of chronic tubulin tyrosination in a HCM mouse model (Mybpc3-knock-in; KI), in human HCM cardiomyocytes and in SVBP-deficient human engineered heart tissues (EHTs). Methods and ResultsAAV9-mediated TTL transfer was applied in neonatal wild-type (WT) rodents and 3-week-old KI mice and in HCM human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. We show that i) TTL for 6 weeks dose-dependently reduced dTyr-tub and improved contractility without affecting cytosolic calcium transients in WT cardiomyocytes; ii) TTL for 12 weeks improved diastolic filling, cardiac output and stroke volume and reduced stiffness in KI mice; iii) TTL for 10 days normalized cell hypertrophy in HCM hiPSC-cardiomyocytes; iv) TTL induced a marked transcription and translation of several tubulins and modulated mRNA or protein levels of components of mitochondria, Z-disc, ribosome, intercalated disc, lysosome and cytoskeleton in KI mice; v) SVBP-deficient EHTs exhibited reduced dTyr-tub levels, higher force and faster relaxation than TTL-deficient and WT EHTs. RNA-seq and mass spectrometry analysis revealed distinct enrichment of cardiomyocyte components and pathways in SVBP-KO vs. TTL-KO EHTs. ConclusionThis study provides the first proof-of-concept that chronic activation of tubulin tyrosination in HCM mice and in human EHTs improves heart function and holds promise for targeting the non-sarcomeric cytoskeleton in heart disease.

physiology↗

bioRxiv2020

An improved comprehensive strategy for deep and quantitative N-glycomics based on optimization of sample preparation, isotope-based data quality control and quantification, new N-glycan libraries and new algorithms

Withdrawal statement"The authors have withdrawn their manuscript because the authors need to re-organize the data and writing, meanwhile more experimental evidence from human cellular N-glycome will be added to support their viewpoints. In this preprint, only one human cell line, Acute Promyelocytic Leukemia (APL) cells, was deeply investigated to show the N-glycome landscape. To provide the shared features of human N-glycome, more human cells should be investigated. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author."

biochemistry↗

bioRxiv2020

Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication

Cytomegaloviruses (CMV) infect many different cell types and tissues in their respective hosts. Monocytes and macrophages play an important role in CMV dissemination from the site of infection to target organs. Moreover, macrophages are specialized in pathogen sensing and respond to infection by secreting cytokines and interferons. In murine cytomegalovirus (MCMV), a model for human cytomegalovirus, several genes required for efficient replication in macrophages have been identified, but their specific functions remain poorly understood. Here we show that MCMV m139, a gene of the conserved US22 gene family, encodes a protein that interacts with the DEAD box helicase DDX3, a protein involved in pathogen sensing and interferon (IFN) induction, and the E3 ubiquitin ligase UBR5. DDX3 and UBR5 also participate in the transcription, processing, and translation of a subset of cellular mRNAs. We show that m139 inhibits DDX3-mediated IFN-{beta} induction and is necessary for efficient viral replication in bone-marrow derived macrophages. In vivo, m139 is crucial for viral dissemination to local lymph nodes and to the salivary glands. An m139-deficient MCMV also replicated to lower titers in SVEC4-10 endothelial cells. This replication defect was not accompanied by increased IFN-{beta} transcription, but was rescued by knockout of either DDX3 or UBR5. Moreover, m139 co-localized with DDX3 and UBR5 in viral replication compartments in the cell nucleus. These results suggest that m139 inhibits DDX3-mediated IFN-{beta} production in macrophages and antagonizes DDX3 and UBR5-dependent functions related to RNA metabolism in endothelial cells. Author SummaryHuman cytomegalovirus is an opportunistic pathogen that causes severe infections in immunocompromised individuals. The virus infects certain types, such as macrophages and endothelial cells, to ensure its dissemination within the body. Little is known about the viral factors that promote a productive infection of these cell types. The identification of critical viral factors and the molecular pathways they target can lead to the development of novel antiviral treatment strategies. Using the mouse cytomegalovirus as a model, we studied the viral m139 gene, which is important for virus replication in macrophages and endothelial cells and for dissemination in the mouse. This gene encodes a protein that interacts with the host proteins DDX3 and UBR5. Both proteins are involved in gene expression, and the RNA helicase DDX3 also participates in mounting an innate antiviral response. By interacting with DDX3 and UBR5, m139 ensures efficient viral replication in endothelial cells. Importantly, we identify m139 as a new viral DDX3 inhibitor, which curtails the production of interferon in macrophages.

microbiology↗