A5090986952- Single-cell and spatial transcriptomics
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Renal Diseases and Glomerulopathies
- Vasculitis and related conditions
- Amyotrophic Lateral Sclerosis Research
- Ferroptosis and cancer prognosis
- Neurogenesis and neuroplasticity mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Renal and related cancers
- Cholinesterase and Neurodegenerative Diseases
- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- Atherosclerosis and Cardiovascular Diseases
- Mast cells and histamine
- Tissue Engineering and Regenerative Medicine
- AI in cancer detection
- Domain Adaptation and Few-Shot Learning
- IL-33, ST2, and ILC Pathways
- Amoebic Infections and Treatments
- Autoimmune Bullous Skin Diseases
- Prion Diseases and Protein Misfolding
- Cell Image Analysis Techniques
Universität Hamburg
2022-2025
University Medical Center Hamburg-Eppendorf
2022-2025
Abstract Neural–tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients’ survival. use reference signatures cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites upregulation genes associated with synaptic integration. Single-cell transcriptomic...
Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes comprehensive multiomic approach to investigate the early sex-specific molecular mechanisms underlying ALS. By analyzing prefrontal cortex of 51 patients with sporadic ALS 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, FUS-ALS), we have uncovered significant alterations associated disease. Here, show that...
Abstract The longitudinal transition of phenotypes is pivotal in glioblastoma treatment resistance and DNA methylation emerged as an important tool for classifying phenotypes. We aimed to characterize subclass heterogeneity during progression assess its clinical impact. Matched tissues from 47 patients were subjected profiling, including CpG-site alterations, tissue serum deconvolution, mass spectrometry, immunoassay. Effects characteristics on temporal changes outcomes studied. Among...
Differences in immune response between men and women may influence the outcome of infectious diseases. Intestinal infection with Entamoeba histolytica leads to hepatic amebiasis, which is more common males. Previously, we reported that innate cells contribute liver damage males murine model for amebiasis. Here, focused on influences sex androgens neutrophils particular. Infection associated neutrophil accumulation was higher male than female mice further increased after testosterone...
Single-cell sequencing provides detailed insights into biological processes including cell differentiation and identity. While providing deep cell-specific information, the method suffers from technical constraints, most notably a limited number of expressed genes per cell, which leads to suboptimal clustering type identification.Here, we present DISCERN, novel generative network that precisely reconstructs missing single-cell gene expression using reference dataset. DISCERN outperforms...
The identification of biologically meaningful domains is a central step in the analysis spatial transcriptomic data. Following Occam's razor, we show that simple PCA-based algorithm for unsupervised domain rivals performance ten competing state-of-the-art methods across six single-cell datasets. Our reductionist approach, NichePCA, provides researchers with intuitive interpretation and excels execution speed, robustness, scalability. code available at https://github.com/imsb-uke/nichepca....
Tissue-resident memory T (TRM) cells are a specialized cell population that reside in tissues and provide rapid protective response upon activation. Here, we showed human mouse CD4+ TRM existed poised state stored messenger RNAs encoding proinflammatory cytokines without protein production. At steady state, cytokine mRNA translation was suppressed by the integrated stress (ISR) pathway. Upon activation, central ISR regulator, eIF2α, dephosphorylated translated for immediate Genetic or...
Extracellular vesicles (EVs) are small capsular bodies released by cells, mediating responses in intercellular communication. The role of EVs Aβ pathology spreading the Alzheimer's disease (AD) brain has been evidenced, although whether this occurs due to co-transportation peptides or contribution other factors, such as EV-associated transcripts, remains uncertain. In vitro studies miRNA cargo neuron-derived extracellular (NDEVs) show that hyperexpression alters transcriptomic profile;...
Single-cell spatial transcriptomics enables precise mapping of cellular states and functional domains within their native tissue environment. These often exist at multiple scales, with larger encompassing smaller ones, reflecting the hierarchical organization biological systems. However, identification these domain hierarchies has been hardly explored due to lack appropriate computational methods. In this work, we present SCALE, an unsupervised algorithm for multi-scale in data. SCALE...
Journal Article Targeted anticonvulsive treatment of IDH-wildtype glioblastoma based on DNA methylation subclasses Get access Richard Drexler, Drexler Department Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Jennifer Göttsche, Göttsche Thomas Sauvigny, Sauvigny Ulrich Schüller, Schüller Institute Neuropathology, GermanyDepartment Pediatric Hematology and Oncology, Research Children's...
Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is nascent. We present an epigenetically defined neural signature of glioblastoma that independently affects patients' survival. use reference signatures cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites upregulation genes associated with synaptic integration. Single-cell transcriptomic analysis...
<title>Abstract</title> Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (ANCA-GN). To date, treatment of most patients with ANCA-GN relies on unspecific immunosuppressive agents harbor serious adverse effects and are sometimes only partially effective. By performing spatial single cell transcriptome analysis, we characterized inflammatory niches the kidneys...
Prostate cancer (PCa) is among the most common cancers in men and its diagnosis requires histopathological evaluation of biopsies by human experts. While several recent artificial intelligence-based (AI) approaches have reached expert-level PCa grading, they often display significantly reduced performance on external datasets. This can be caused variations sample preparation, for instance staining protocol, section thickness, or scanner used. Another limiting factor contemporary AI-based...
In this study, we addressed challenges in integrating clinically obtained kidney biopsies into everyday clinical routines. Using porcine kidneys, evaluated preservation media (RNAlater and CellCover) versus snap freezing for multi-omics processing. Our analyses highlighted RNAlater’s suitability single-nucleus RNA sequencing, proteome analysis histopathological evaluation. Only metabolomics are currently restricted to snap-frozen biopsies. research established a cryopreservation protocol...
Rapidly progressive glomerulonephritis (RPGN) is the most aggressive group of autoimmune kidney disease with worst prognosis. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, anti-glomerular basement membrane (anti-GBM) and lupus nephritis are common causes RPGN characterized by formation glomerular crescents infiltration leukocytes that eventually lead to glomerulosclerosis failure. In this work, we used high-resolution spatial transcriptomics 32 ANCA, 19 nephritis, 6...
Abstract Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and lacks effective disease-modifying treatments. Here, we performed a multiomic analysis of prefrontal cortex 51 patients with sporadic ALS 50 control subjects, as well four transgenic mouse models C9orf72-, SOD1-, TDP-43-, FUS-ALS to characterize early sex-specific mechanisms in ALS. Integrated analyses transcriptomes, (phospho)proteomes, miRNAomes revealed more pronounced changes males. We identified...
Abstract Cell deconvolution is the estimation of cell type fractions and type-specific gene expression from mixed data with unknown composition. In biomedical research, deconvolution, which a source separation task, used to obtain mechanistic diagnostic insights into human disease. An unmet challenge in however, scarcity realistic training strong domain shift observed synthetic that contemporary methods. Here, we hypothesize simultaneous consistency regularization target domains will improve...
Abstract Background 5-aminolevulinic acid (5-ALA) fluorescence-guided resection increases the percentage of complete CNS tumor resections and improves progression-free survival IDH-wildtype glioblastoma patients. A small subset shows no 5-ALA fluorescence. An explanation for these cases is missing. In this study, we used DNA methylation profiling to further characterize non-fluorescent glioblastomas. Methods Patients with newly diagnosed recurrent that underwent surgery were analyzed. The...
The identification of biologically meaningful domains is a central step in the analysis spatial transcriptomic data. Following Occam's razor, we show that simple PCA-based algorithm for domain rivals performance ten competing state-of-the-art methods across six single-cell datasets. Our reductionist approach, NichePCA, provides researchers with intuitive interpretation and excels execution speed, robustness, scalability.