A5051832409- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Nanopore and Nanochannel Transport Studies
- Gene Regulatory Network Analysis
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Cancer Cells and Metastasis
- Genomics and Phylogenetic Studies
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Metabolism, Diabetes, and Cancer
- Single-cell and spatial transcriptomics
- Inflammatory mediators and NSAID effects
- Magnetic Field Sensors Techniques
- Gene expression and cancer classification
- Mitochondrial Function and Pathology
- Cell Image Analysis Techniques
- Computational Drug Discovery Methods
- Inertial Sensor and Navigation
- Wireless Sensor Networks for Data Analysis
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Microbial Metabolic Engineering and Bioproduction
- Pharmacogenetics and Drug Metabolism
- PI3K/AKT/mTOR signaling in cancer
Heidelberg University
2019-2024
University Hospital Heidelberg
2019-2024
German Centre for Cardiovascular Research
2022-2024
Klaus Tschira Foundation
2022
RWTH Aachen University
2019-2021
Joint Research Centre
2019-2021
Humboldt-Universität zu Berlin
2021
Charité - Universitätsmedizin Berlin
2020-2021
Freie Universität Berlin
2021
European Molecular Biology Organization
2020
Abstract Elevated production of collagen-rich extracellular matrix is a hallmark cancer-associated fibroblasts (CAFs) and central driver cancer aggressiveness. Here we find that proline, highly abundant amino acid in collagen proteins, newly synthesized from glutamine CAFs to make tumour breast xenografts. PYCR1 key enzyme for proline synthesis expressed the stroma patients CAFs. Reducing levels sufficient reduce production, growth metastatic spread vivo cell proliferation vitro. Both...
Abstract While gene expression profiling is commonly used to gain an overview of cellular processes, the identification upstream processes that drive changes remains a challenge. To address this issue, we introduce CARNIVAL, causal network contextualization tool which derives architectures from footprints. CARNIVAL (CAusal Reasoning pipeline for Network using Integer VALue programming) integrates different sources prior knowledge including signed and directed protein–protein interactions,...
Post-translational modifications of proteins play an important role in the regulation cellular processes. The mass spectrometry analysis proteome offers huge potential for study how protein inhibitors affect phosphosignaling mechanisms inside cells. We have recently proposed PHONEMeS, a method that uses high-content shotgun phosphoproteomic data to build logical network models signal perturbation flow. However, its original implementation, PHONEMeS was computationally demanding and only used...
The molecular changes induced by perturbations such as drugs and ligands are highly informative of the intracellular wiring. Our capacity to generate large datasets is increasing steadily. A useful way extract mechanistic insight from data integrating them with a prior knowledge network signalling obtain dynamic models. CellNOpt collection Bioconductor R packages for building logic models perturbation networks. We have recently developed new components refined existing ones keep up...
Nanopore long-read sequencing enables real-time monitoring and controlling of individual nanopores. This allows us to enrich or deplete specific sequences in DNA a process called “adaptive sampling.” So far, adaptive sampling (AS) was not applicable the direct RNA. Here, we show that AS is feasible useful for RNA (DRS), which has its technical biological challenges. Using well-controlled vitro transcript-based model system, identify essential characteristics parameter settings DRS, as...
Endothelins (EDN) are peptide hormones that activate a GPCR signalling system and contribute to several diseases, including hypertension cancer. Current knowledge about EDN is fragmentary, no systems level understanding available. We investigated phosphoproteomic changes caused by endothelin B receptor (ENDRB) activation in the melanoma cell lines UACC257 A2058 built an integrated model of EDNRB from phosphoproteomics data. More than 5,000 unique phosphopeptides were quantified. induced...
TP53, the
Abstract Multi-omics datasets can provide molecular insights beyond the sum of individual omics. Diverse tools have been recently developed to integrate such datasets, but there are limited strategies systematically extract mechanistic hypotheses from them. Here, we present COSMOS (Causal Oriented Search Multi-Omics Space), a method that integrates phosphoproteomics, transcriptomics, and metabolics datasets. combines extensive prior knowledge signaling, metabolic, gene regulatory networks...
Abstract Motivation Alternative RNA splicing plays a crucial role in defining protein function. However, despite its relevance, there is lack of tools that characterize effects on interaction networks mechanistic manner (i.e. presence or absence protein–protein interactions due to splicing). To fill this gap, we present Linear Integer programming for Network reconstruction using transcriptomics and Differential data Analysis (LINDA) as method integrates resources domain–domain interactions,...
Abstract While gene expression profiling is commonly used to gain an overview of cellular processes, the identification upstream processes that drive changes remains a challenge. To address this issue, we introduce CARNIVAL, causal network building tool which derives architectures from footprints. CARNIVAL (CAusal Reasoning pipeline for Network using Integer VALue programming) integrates different sources prior knowledge, including signed and directed protein-protein interactions,...
PGE 2 receptors elicit shared, receptor-specific, and cell type–specific downstream signaling in T cells.
Abstract Background Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. We address need an intuitive interactive web application to explore transcriptional signatures with this work. Methods reanalysed Myocardial Applied Genomics Network dataset, one largest publicly available left ventricular samples from patients dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well...
The reliable authentication of cell lines is a prerequisite for the reproducibility and replicability experiments. A common method line fragment length analysis (FLA) short-tandem repeats (STR) by capillary electrophoresis. However, this technique not always accessible often costly. Using microfluidic electrophoresis system, we analyzed quality integrity different murine STR profiling. As proof concept, isolated immortalized hematopoietic progenitor cells (HPC) various genotypes through...
TElevated production of collagen-rich extracellular matrix (ECM) is a hallmark cancer associated fibroblasts (CAFs) and central driver aggressiveness. How to target ECM oppose yet unclear, since targeting CAFs has been shown restrain but also promote progression. Metabolic rewiring CAFs. Here we find that proline, which highly abundant amino acid in collagen proteins, newly synthesised from glutamine make tumour breast xenografts, its elevated PYCR1 the rate-limiting enzyme for proline...
Abstract Motivation The molecular changes induced by perturbations such as drugs and ligands are highly informative of the intracellular wiring. Our capacity to generate large data-sets is increasing steadily new experimental approaches developed. A useful way extract mechanistic insight from data integrating them with a prior knowledge network signalling obtain dynamic models. Logic models scale better size than alternative kinetic models, while keeping interpretation model simple, making...
Abstract Time-course multi-omics data of a murine model progressive heart failure induced by transverse aortic constriction (TAC) provide insights into the molecular mechanisms that are causatively involved in contractile and structural cardiac remodelling. We employ Illumina-based transcriptomics, Nanopore sequencing, mass spectrometry-based proteomics on samples from left ventricle (LV) right (RV, RNA only) at 1, 7, 21, 56 days following TAC Sham surgery. Here, we present TACOMA, as an...
Abstract Time-course multi-omics data of a murine model progressive heart failure (HF) induced by transverse aortic constriction (TAC) provide insights into the molecular mechanisms that are causatively involved in contractile and structural cardiac remodelling. We employ Illumina-based transcriptomics, Nanopore sequencing mass spectrometry-based proteomics on samples from left ventricle (LV) right (RV, RNA only) at 1, 7, 21 56 days following TAC Sham surgery. Here, we present Transverse...
Cellular activity and responses to stimuli are governed through an elaborated communication process called cell signalling. The modelling of signalling mechanisms has the potential help us understand regulatory processes determining cellular behaviour. One approach derive models networks is from data alone. Another one use prior knowledge (PKN's) derived literature or experts' build that trained data. Both approaches have limitations. Data-driven methods can infer many false-positive...
Abstract Cancer-associated fibroblasts (CAFs) play fundamental roles in cancer and are emerging as therapeutic target tumors with extensive stromal regions those for which there limited targeted therapies against the cells, such ovarian cancer. A unique feature of CAFs is their ability to secrete abundant collagen-rich extracellular matrix (ECM) that promotes desmoplastic reaction accompanies tumor progression drives growth metastasis. Altered metabolism a hallmark cancer, understanding...
Abstract ONT long-read sequencing provides real-time monitoring and controlling of individual nanopores. Adaptive sampling enriches or depletes specific sequences in Nanopore DNA sequencing, but was not applicable to direct RNA so far. Here, we identify essential parameter settings for (DRS). We demonstrate the superior performance depletion over enrichment show that adaptive efficiently transcripts transcriptome-wide applications. Specifically, applied our approach polyA+ samples from human...