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65 result(s) for "Anton, Mihail"
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A consensus S. cerevisiae metabolic model Yeast8 and its ecosystem for comprehensively probing cellular metabolism
Genome-scale metabolic models (GEMs) represent extensive knowledgebases that provide a platform for model simulations and integrative analysis of omics data. This study introduces Yeast8 and an associated ecosystem of models that represent a comprehensive computational resource for performing simulations of the metabolism of Saccharomyces cerevisiae ––an important model organism and widely used cell-factory. Yeast8 tracks community development with version control, setting a standard for how GEMs can be continuously updated in a simple and reproducible way. We use Yeast8 to develop the derived models panYeast8 and coreYeast8, which in turn enable the reconstruction of GEMs for 1,011 different yeast strains. Through integration with enzyme constraints (ecYeast8) and protein 3D structures (proYeast8 DB ), Yeast8 further facilitates the exploration of yeast metabolism at a multi-scale level, enabling prediction of how single nucleotide variations translate to phenotypic traits. Genome-scale metabolic models provide a platform to study metabolism through simulations and analysis of omics data. Here the authors introduce Yeast8 with its model ecosystem, a comprehensive computational resource for simulating the metabolism of Saccharomyces cerevisiae .
Genome-scale metabolic network reconstruction of model animals as a platform for translational research
Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer’s disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.
Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0
Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into such models was first enabled by the GECKO toolbox, allowing the study of phenotypes constrained by protein limitations. Here, we upgrade the toolbox in order to enhance models with enzyme and proteomics constraints for any organism with a compatible GEM reconstruction. With this, enzyme-constrained models for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus are generated to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions reveal that upregulation and high saturation of enzymes in amino acid metabolism are common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO is expanded with an automated framework for continuous and version-controlled update of enzyme-constrained GEMs, also producing such models for Escherichia coli and Homo sapiens . In this work, we facilitate the utilization of enzyme-constrained GEMs in basic science, metabolic engineering and synthetic biology purposes.
Reconstruction, simulation and analysis of enzyme-constrained metabolic models using GECKO Toolbox 3.0
Genome-scale metabolic models (GEMs) are computational representations that enable mathematical exploration of metabolic behaviors within cellular and environmental constraints. Despite their wide usage in biotechnology, biomedicine and fundamental studies, there are many phenotypes that GEMs are unable to correctly predict. GECKO is a method to improve the predictive power of a GEM by incorporating enzymatic constraints using kinetic and omics data. GECKO has enabled reconstruction of enzyme-constrained metabolic models (ecModels) for diverse organisms, which show better predictive performance than conventional GEMs. In this protocol, we describe how to use the latest version GECKO 3.0; the procedure has five stages: (1) expansion from a starting metabolic model to an ecModel structure, (2) integration of enzyme turnover numbers into the ecModel structure, (3) model tuning, (4) integration of proteomics data into the ecModel and (5) simulation and analysis of ecModels. GECKO 3.0 incorporates deep learning-predicted enzyme kinetics, paving the way for improved metabolic models for virtually any organism and cell line in the absence of experimental data. The time of running the whole protocol is organism dependent, e.g., ~5 h for yeast. Key points Genome-scale metabolic models have the potential to predict changes in phenotype resulting from different environmental conditions. Their predictive power can be improved by including more information about the enzyme kinetics. GECKO is a program that gives users an automated and manual mechanism to incorporate relevant data. The protocol also describes how to tune the program to compensate for incorrect or missing values. Genome-scale metabolic models enable mathematical exploration of metabolism under various defined conditions. This protocol describes GECKO, a method for enhancing a genome-scale metabolic model with enzymatic constraints using kinetic and omics data (e.g., proteomics).
Sustainable Urban Branding: Insights from Rasnov’s Case Study
This study investigates the determinants of urban brand perception, with a focus on the city of Rasnov. The research aims to identify elements of local identity, assess residents’ satisfaction with urban infrastructure and quality of life, and explore attitudes towards sustainable tourism and the city’s public image. Methodologically, the study employs a quantitative approach through an online survey administered to active social media users, particularly members of local Facebook groups. A total of 627 respondents were selected using probabilistic cluster sampling. The findings reveal a significant correlation between emotional attachment to the city and favorable perceptions of urban life, underpinned by factors such as personal memories, a sense of belonging, and perceived urban tranquility. While residents report moderate satisfaction with urban infrastructure, notable concerns persist regarding the maintenance of public spaces, availability of employment opportunities, and the efficiency of public transportation. Furthermore, the level of awareness concerning the city’s branding strategy is relatively low. Key assets identified as essential for urban promotion include the Râșnoavei Keys, the Valea Cărbunării Sports Complex, local mountain trails, and the Rasnov Citadel. Respondents advocate for enhanced public communication regarding the urban branding strategy and emphasize the importance of community engagement in shaping and promoting the city’s image in alignment with residents’ aspirations.
Mapping European Countries’ Resilience to Cognitive Warfare
This study maps European countries’ resilience to cognitive warfare by developing a cross-national composite measure. The framework integrates three pillars: information ecology, institutional-digital capacity, and socioeconomic context—drawing on a systemic perspective linking social structures to societal functions. Publicly available secondary indicators are compiled from online sources for EU (European Union) and EEA (European Economics Area) states. The dataset is examined through descriptive analysis, association testing, multivariate modelling, dimensionality reduction to derive a composite resilience score, and unsupervised clustering to produce a country typology. Indicators capture governance effectiveness, e-government maturity, public-sector AI (Artificial Intelligence) readiness, digital connectivity and infrastructure, media freedom and broader media-ecosystem quality, academic freedom, and socioeconomic vulnerabilities such as youth labour market exclusion. Results show that resilience aligns most strongly with institutional capacity and governance performance; a healthy ecology acts as a reinforcing layer. Digital infrastructure appears necessary but insufficient without capable, credible institutions and coherent public policy. Socioeconomic vulnerabilities tend to erode resilience and heighten susceptibility to hostile cognitive influence. The study concludes that policy efforts should prioritise governance integrity and effectiveness, end-to-end digital government, responsible public-sector AI capability, and safeguards for media and academic autonomy, alongside measures that improve youth inclusion.
Strengthening bioinformatics education: e-learning initiatives across ELIXIR Nodes and Communities
The rapid evolution of bioinformatics and data-driven life sciences necessitates widespread, effective training solutions capable of transcending geographical and institutional boundaries. ELIXIR, as a pan-European bioinformatics research infrastructure, has strategically embraced e-learning methodologies to meet this challenge. This white paper systematically reviews the current landscape of e-learning initiatives across various ELIXIR Nodes and Communities, detailing both historical developments and contemporary practices. It identifies core attributes and desirable features of effective e-learning, presenting an analysis of diverse educational platforms and the deployment of Learning Management Systems (LMS) within ELIXIR’s framework. Emphasis is placed on the interactive, open-access, and sustainable nature of these resources, exemplified by platforms such as the Training e-Support System (TeSS) and the ELIXIR-SI eLearning Platform (EeLP). The paper highlights critical advancements toward standardization and interoperability through initiatives such as the adoption of SCORM protocols, facilitating resource reuse across Nodes. Additionally, the integration of e-learning into broader educational strategies—such as hybrid learning environments and structured learning paths—is examined. Finally, future directions are discussed, including strategies for integrating e-learning with traditional training methods, enhancing trainer expertise, and further expanding the availability and FAIRification of bioinformatics training resources.
Author Correction: A consensus S. cerevisiae metabolic model Yeast8 and its ecosystem for comprehensively probing cellular metabolism
An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Systems Biology in ELIXIR: modelling in the spotlight version 2; peer review: 2 approved, 1 approved with reservations
In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.
Systems Biology in ELIXIR: modelling in the spotlight version 1; peer review: 1 approved, 2 approved with reservations
In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.