A5068859428- Bioinformatics and Genomic Networks
- Protein Structure and Dynamics
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- Gene Regulatory Network Analysis
- RNA Research and Splicing
- Machine Learning in Bioinformatics
- RNA and protein synthesis mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Structure and Function
- Biomedical Text Mining and Ontologies
- RNA modifications and cancer
- Osteoarthritis Treatment and Mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Computational Drug Discovery Methods
- Bacterial Genetics and Biotechnology
- Herpesvirus Infections and Treatments
- Clostridium difficile and Clostridium perfringens research
- Cardiac Structural Anomalies and Repair
- Genomics and Chromatin Dynamics
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
Ludwig-Maximilians-Universität München
2016-2025
Institute of Bioinformatics and Systems Biology
2016-2022
Freie Universität Berlin
2021
Ruhr University Bochum
2021
Kansas State University
2021
University of Kansas Medical Center
2021
Southern University of Science and Technology
2021
Enamine (Ukraine)
2021
Institute of Organic Chemistry
2021
Maria Curie-Skłodowska University
2021
The discovery of regulatory pathways, signal cascades, metabolic processes or disease models requires knowledge on individual relations like e.g. physical interactions between genes and proteins. Most mentioned in the free text biomedical publications are not yet contained structured databases.We developed RelEx, an approach for relation extraction from text. It is based natural language preprocessing producing dependency parse trees applying a small number simple rules to these trees. We...
RNA levels in a cell are determined by the relative rates of synthesis and decay. State-of-the-art transcriptional analyses only employ total cellular RNA. Therefore, changes cannot be attributed to or decay, temporal resolution is poor. Recently, it was reported that newly transcribed can biosynthetically labeled for 1-2 h using thiolated nucleosides, purified from subjected microarray analysis. However, order study signaling events at molecular level, analysis occurring within minutes...
Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics available against CoVs. Knowledge host cell proteins take part pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach...
Abstract Objective Despite many research efforts in recent decades, the major pathogenetic mechanisms of osteoarthritis (OA), including gene alterations occurring during OA cartilage degeneration, are poorly understood, and there is no disease‐modifying treatment approach. The present study was therefore initiated order to identify differentially expressed disease‐related genes potential therapeutic targets. Methods This investigation consisted a large expression profiling performed based on...
Abstract Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription RNA processing their impact on translation can be analysed single experimental setting by applying 4sU-tagging of newly transcribed ribosome profiling to lytic HSV-1 infection. Unexpectedly, find triggers the disruption termination cellular, but not viral, genes. This results extensive tens thousands nucleotides beyond...
Atheroprogression is a consequence of nonresolved inflammation, and currently comprehensive overview the mechanisms preventing resolution missing. However, in acute known to be orchestrated by switch from inflammatory resolving lipid mediators. Therefore, we hypothesized that lesional mediator imbalance favors atheroprogression.To understand balance during atheroprogression establish an interventional strategy based on delivery mediators.Aortic profiling aortas Apoe-/- mice fed high-fat diet...
Abstract Background Identification of gene and protein names in biomedical text is a challenging task as the corresponding nomenclature has evolved over time. This led to multiple synonyms for individual genes proteins, well that may be ambiguous with other or general English words. The Gene List Task BioCreAtIvE challenge evaluation enables comparison systems addressing problem name identification on common benchmark data. Methods ProMiner system uses pre-processed synonym dictionary...
Abstract Motivation: Large scale gene expression data are often analysed by clustering genes based on alone, though a priori knowledge in the form of biological networks is available. The use this additional information promises to improve exploratory analysis considerably. Results: We propose constructing distance function which combines from and networks. Based function, we compute joint vertices network. This general approach elaborated for metabolic define graph such combine it with...
The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading the expression of up 30 structural and non-structural protein products. functions a large number viral ORFs are poorly understood or unknown. In order gain more insight into modes action interaction different proteins, we cloned ORFeome performed genome-wide analysis for intraviral interactions intracellular localization. 900 pairwise were tested by...
RNA levels in a cell are regulated by the relative rates of synthesis and decay. We recently developed new approach for measuring both decay single experimental setting biosynthetic labeling newly transcribed RNA. Here, we show that this provides measurements half-lives from microarray data with so far unreached accuracy. Based on such human B-cells mouse fibroblasts, identified conserved regulatory principles large number biological processes. different patterns between functionally similar...
Cytomegaloviruses express large amounts of viral miRNAs during lytic infection, yet, they only modestly alter the cellular miRNA profile. The most prominent alteration upon murine cytomegalovirus (MCMV) infection is rapid degradation miR-27a and miR-27b. Here, we report that this regulation mediated by ∼1.7 kb spliced highly abundant MCMV m169 transcript. Specificity to miR-27a/b a single, apparently optimized, binding site located in its 3'-UTR. This easily efficiently retargeted other...
The availability of multiple bacterial genome sequences has revealed a surprising extent variability among strains the same species. human gastric pathogen Helicobacter pylori is known as one most genetically diverse We have compared sequence duodenal ulcer strain P12 and six other H. genomes to elucidate genetic repertoire evolution mechanisms this In agreement with previous findings, we estimate that core comprises about 1200 genes possesses an open pan-genome. Strain-specific are...
Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing variety different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 170 open reading frames. We previously reported the protein interaction networks two herpesviruses, varicella-zoster virus (VZV) Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional species, herpes simplex 1 (HSV-1), murine cytomegalovirus...
RNA synthesis and decay rates determine the steady-state levels of cellular RNAs. Metabolic tagging newly transcribed by 4-thiouridine (4sU) can reveal relative contributions rates. The kinetics processing, however, had so far remained unresolved. Here, we show that ultrashort 4sU-tagging not only provides snapshot pictures eukaryotic gene expression but, when combined with progressive RNA-seq, reveals global processing at nucleotide resolution. Using this method, identified classes rapidly...
Gene expression is regulated in a context-dependent, cell-type-specific manner. Condition-specific transcription dependent on the presence of factors (TFs) that can activate or inhibit its target genes (global context). Additional factors, such as chromatin structure, histone, DNA modifications, also influence activity individual (individual The role global and context for post-transcriptional regulation has not systematically been investigated large scale poorly understood. Here we show...
Abstract Motivation: To improve the understanding of molecular regulation events, various approaches have been developed for deducing gene regulatory networks from mRNA expression data. Results: We present a new score network inference, η2, that is derived an analysis variance. Candidate transcription factor:target (TF:TG) relationships are assumed more likely if TF and TG mutually dependent in at least subset examined experiments. evaluate this dependency by non-parametric, non-linear...
Although gene set enrichment analysis has become an integral part of high-throughput expression data analysis, the assessment methods remains rudimentary and ad hoc. In absence suitable gold standards, evaluations are commonly restricted to selected datasets biological reasoning on relevance resulting enriched sets.We develop extensible framework for reproducible benchmarking based defined criteria applicability, prioritization detection relevant processes. This incorporates a curated...
Highlights•The HSR is modular and tuned to the severity of stress•90% upregulation under stress required keep protein levels constant•Protein loss replenished by translation•Aggregation processes shape sublethal heat responseSummaryLife resilient because living systems are able respond elevated temperatures with an ancient gene expression program called shock response (HSR). In yeast, transcription hundreds genes upregulated at temperatures. Besides protection conferred chaperones, function...
Neutrophils provide a critical line of defense in immune responses to various pathogens, inflicting self-damage upon transition hyperactivated, procoagulant state. Recent work has highlighted proinflammatory neutrophil phenotypes contributing lung injury and acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). Here, we use state-of-the art mass spectrometry–based proteomics transcriptomic correlative analyses as well functional vitro vivo studies...
Alternative macrophage activation, which relies on mitochondrial oxidative metabolism, plays a central role in the resolution of inflammation and prevents atherosclerosis. Moreover, macrophages handle large amounts cholesterol triglycerides derived from engulfed modified lipoproteins during Although several microRNAs regulate polarization, microRNA-generating enzyme Dicer activation atherosclerosis is unknown.To evaluate atherosclerosis, Apoe-/- mice with or without macrophage-specific...
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to pneumonia, but also thrombotic complications and non-pulmonary organ failure. Recent studies suggest intravascular neutrophil activation subsequent immune cell-triggered immunothrombosis as a central pathomechanism linking the heterogenous clinical picture of disease 2019 (COVID-19). We sought study whether is pathognomonic factor in COVID-19 or general feature (viral) well better understand its upstream...
Abstract The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration multi-omics data. We identify a total 201 transcripts 284 ORFs including all known 46 novel large ORFs. This includes so far unknown ORF in locus deleted FDA-approved oncolytic Imlygic. Multiple transcript isoforms...
Maladaptive, non-resolving inflammation contributes to chronic inflammatory diseases such as atherosclerosis. Because macrophages remove necrotic cells, defective macrophage programs can promote with persistent tissue injury. Here, we investigated the mechanisms sustaining vascular macrophages. Intravital imaging revealed a spatiotemporal niche across beds alongside mural cells (MCs)-pericytes and smooth muscle cells. Single-cell transcriptomics, co-culture, genetic deletion experiments...