- Gene Regulatory Network Analysis
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- COVID-19 epidemiological studies
- Microbial Metabolic Engineering and Bioproduction
- Mathematical and Theoretical Epidemiology and Ecology Models
- CRISPR and Genetic Engineering
- Atomic and Molecular Physics
- Cytokine Signaling Pathways and Interactions
- X-ray Spectroscopy and Fluorescence Analysis
- Mathematical Biology Tumor Growth
- Neuroscience and Neural Engineering
- Simulation Techniques and Applications
- Bioinformatics and Genomic Networks
- Viral Infectious Diseases and Gene Expression in Insects
- Molecular Communication and Nanonetworks
- Single-cell and spatial transcriptomics
- Advanced biosensing and bioanalysis techniques
- Advanced Proteomics Techniques and Applications
- Protein Structure and Dynamics
- Genomics, phytochemicals, and oxidative stress
- Hydrology and Drought Analysis
- bioluminescence and chemiluminescence research
- Gaussian Processes and Bayesian Inference
- Immune Response and Inflammation
University of Freiburg
2016-2024
Czech Academy of Sciences, Institute of Physics
2016
Max-Born-Institute for Nonlinear Optics and Short Pulse Spectroscopy
2013
Reproducibility and reusability of the results data-based modeling studies are essential. Yet, there has been—so far—no broadly supported format for specification parameter estimation problems in systems biology. Here, we introduce PEtab, a which facilitates using Systems Biology Markup Language (SBML) models set tab-separated value files describing observation model experimental data as well parameters to be estimated. We already implemented PEtab support into eight well-established...
Article21 July 2020Open Access Transparent process Disentangling molecular mechanisms regulating sensitization of interferon alpha signal transduction Frédérique Kok orcid.org/0000-0002-7855-1422 Division Systems Biology Signal Transduction, German Cancer Research Center (DKFZ), Heidelberg, Germany Faculty Biosciences, Heidelberg University, Search for more papers by this author Marcus Rosenblatt Institute Physics, University Freiburg, FDM - Freiburg Data Analysis and Modeling, Melissa...
Abstract Awakening of zygotic transcription in animal embryos relies on maternal pioneer factors. The interplay global and specific functions these proteins remains poorly understood. Here, we analyze chromatin accessibility time-resolved single double mutant zebrafish lacking pluripotency factors Pou5f3 Sox19b. We show that two modify a largely independent manner. distinguish four types direct enhancers by differential requirements for or demonstrate changes underlie the expression...
In a wide variety of research fields, dynamic modeling is employed as an instrument to learn and understand complex systems. The differential equations involved in this process are usually non-linear depend on many parameters whose values determine the characteristics emergent system. inverse problem, i.e., inference or estimation parameter from observed data, interest two points view. First, existence point view, dealing with question whether system able reproduce dynamics for any values....
We discuss issues of structural and practical identifiability partially observed differential equations which are often applied in systems biology. The development mathematical methods to investigate non-identifiability has a long tradition. Computationally efficient detect cure it have been developed recently. Practical on the other hand not investigated at same conceptually clear level. argue that is more challenging than when comes modelling experimental data. classical approach based...
Zygotic genome activation (ZGA) in the development of flies, fish, frogs and mammals depends on pioneer-like transcription factors (TFs). Those TFs create open chromatin regions, promote histone acetylation enhancers, activate transcription. Here, we use panel single, double triple mutants for zebrafish activators Pou5f3, Sox19b Nanog, multi-omics mathematical modeling to investigate combinatorial mechanisms activation. We show that Pou5f3 Nanog act differently synergistic antagonistic...
Single-shot time-of-flight spectra for Coulomb explosion of N2 and I2 molecules have been recorded at the Free Electron LASer in Hamburg (FLASH) analysed using a partial covariance mapping technique. The analysis unravels detailed picture all significant pathways, extending up to N4+–N5+ channel nitrogen I8+–I9+ iodine. observation latter is unexpected if only sequential ionization processes from ground state ions are considered. maximum kinetic energy release extracted maps each...
Cells are exposed to oxidative stress and reactive metabolites every day. The Nrf2 signaling pathway responds by upregulation of antioxidants like glutathione (GSH) compensate the insult re-establish homeostasis. Although mechanisms describing interaction between key constituents Nrf2, Keap1 p62 widely reviewed discussed in literature, quantitative dynamic models bringing together these with time-resolved data limited. Here, we present an ordinary differential equation (ODE) based model...
Ordinary differential equation models have become a wide-spread approach to analyze dynamical systems and understand underlying mechanisms. Model parameters are often unknown be estimated from experimental data, e.g.~by maximum-likelihood estimation. In particular, of biological contain large number parameters. To reduce the dimensionality parameter space, steady-state information is incorporated in estimation process. For non-linear models, analytical calculation typically leads...
Biological systems are frequently analyzed by means of mechanistic mathematical models. In order to infer model parameters and provide a useful that can be employed for understanding hypothesis testing, the is often calibrated on quantitative, time-resolved data. To do so, it typically important compare experimental measurements over broad time ranges various conditions, e.g. perturbations biological system. However, most established techniques such as Western blot, or quantitative real-time...
Synthetic biology applies concepts from electrical engineering and information processing to endow cells with computational functionality. Transferring the underlying molecular components into materials wiring them according topologies inspired by electronic circuit boards has yielded systems that perform selected operations. However, limited functionality of available building blocks is restricting implementation advanced information-processing circuits materials. Here, a set protease-based...
In lung cancer a deregulation of Transforming Growth Factor-β (TGFβ) signaling has been observed. Yet, the impact TGFβ in squamous cell carcinoma (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies showed that stimulation LUSC line SK-MES1 with results an increase migratory invasive properties. The analysis dynamics gene expression by next-generation sequencing revealed orchestrates upregulation numerous motility- actin cytoskeleton-related genes. Among...
Abstract Zygotic genome activation (ZGA) in the development of flies, fish, frogs and mammals depends on pioneer-like transcription factors (TFs). Those TFs create open chromatin regions, promote histone acetylation enhancers, activate transcription. Here, we use panel single, double triple mutants for zebrafish activators Pou5f3, Sox19b Nanog, multi-omics mathematical modeling to investigate combinatorial mechanisms activation. We show that Pou5f3 Nanog act differently synergistic...
Abstract In a wide variety of research elds, dynamic modeling is employed as an instrument to learn and understand complex systems. The differential equations involved in this process are usually non-linear depend on many parameters whose values decide upon the characteristics emergent system. inverse problem, i.e. inference or estimation parameter from observed data, interest two points view. First, existence point view, dealing with question whether system able reproduce dynamics for any...
Ordinary differential equations are frequently employed for mathematical modeling of biological systems. The identification mechanisms that specific to certain cell types is crucial building useful models and gain insights into the underlying processes. Regularization techniques have been proposed applied identify two types, e.g., healthy cancer cells, including LASSO (least absolute shrinkage selection operator). However, when analyzing more than these approaches not consistent, require a...
Abstract Awakening of zygotic transcription in animal embryos relies on maternal pioneer factors. The interplay global and specific functions these proteins remains poorly understood. Here, we analyze chromatin accessibility time-resolved single double mutant zebrafish lacking pluripotency factors Pou5f3 Sox19b. We show that two modify a largely independent manner. distinguish four types direct enhancers by differential requirements for or demonstrate changes underlie the expression...
Information-Processing Materials Biohybrid materials that communicate with each other via diffusible inhibitory or activating signals are assembled in a circuit topology inspired by an electronical binary 2-input/4-output decoder. The biomolecular decoder is programmed to convert specific molecular inputs into the release of distinct protease outputs. Such information-processing biohybrid material circuits can be used for computing and sensor signal processing. More details found article...
Viral outbreaks, such as the current COVID-19 pandemic, are commonly described by compartmental models means of ordinary differential equation (ODE) systems. The parameter values these ODE typically unknown and need to be estimated based on accessible data. In order describe realistic pandemic scenarios with strongly varying situations, model parameters assumed time-dependent. While estimation for typical case time-constant does not pose larger issues, determination time-dependent...
Abstract Ordinary differential equations are frequently employed for mathematical modeling of biological systems. The identification mechanisms that specific to certain cell types is crucial building useful models and gain insights into the underlying processes. Regularization techniques have been proposed applied identify two types, e.g., healthy cancer cells, including LASSO (least absolute shrinkage selection operator). However, when analyzing more than these approaches not consistent,...
Abstract Biological systems are frequently analyzed by means of mechanistic mathematical models. In order to infer model parameters and provide a useful that can be employed for understanding hypothesis testing, the is often calibrated on quantitative, time-resolved data. To do so, it typically important compare experimental measurements over broad time ranges various conditions, e.g. perturbations biological system. However, most established techniques such as Western blot, or quantitative...
<b>Rationale:</b> Signal transduction mediated by receptor tyrosine kinases (RTKs) such as EGFR and Met is often altered in lung cancer. Targeting RTKs tumors offers a benefit, however it followed fast resistance. Therefore, in-depth mechanistic understanding of how tumor cells process the information from essential for developing novel intervention strategies. <b>Aim:</b> We aim to understand whether clearance plasma membrane both, degree duration phosphorylation could be modulated encode...
Abstract Synthetic biology applies concepts from electrical engineering and information processing to endow cells with computational functionality. Transferring the underlying molecular components into materials wiring them according topologies inspired by electronic circuit boards has yielded systems that perform selected operations. However, limited functionality of available building blocks is restricting implementation advanced information-processing circuits materials. Here, we engineer...
Abstract Zygotic genome activation (ZGA) in the development of flies, fish, frogs and mammals depends on pioneer-like transcription factors (TFs). Those TFs create open chromatin regions, promote histone acetylation enhancers, activate transcription. Here, we use panel single, double triple mutants for zebrafish activators Pou5f3, Sox19b Nanog, multi-omics mathematical modeling to investigate combinatorial mechanisms activation. We show that Pou5f3 Nanog act differently synergistic...
Describing viral outbreaks, such as the COVID-19 pandemic, often involves employing compartmental models composed of ordinary differential equation (ODE) systems. Estimating parameter values for these ODE is crucial and relies on accessible data. To accurately represent realistic pandemic scenarios with diverse situations, it necessary to consider model parameters time dependent. However, estimating time-dependent parameters, like transition rates in models, notoriously challenging due...