scholarly journals Metabolic Modelling as a Framework for Metabolomics Data Integration and Analysis

Metabolites ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 303 ◽  
Author(s):  
Svetlana Volkova ◽  
Marta R. A. Matos ◽  
Matthias Mattanovich ◽  
Igor Marín de Mas
Keyword(s):  
Data Integration ◽  
Metabolic Networks ◽  
Kinetic Modelling ◽  
Cell Metabolism ◽  
Cell Phenotype ◽  
Metabolomics Data ◽  
Metabolic Modelling ◽  
Metabolomic Data ◽  
Close Relationship ◽  
Underlying Mechanisms

Metabolic networks are regulated to ensure the dynamic adaptation of biochemical reaction fluxes to maintain cell homeostasis and optimal metabolic fitness in response to endogenous and exogenous perturbations. To this end, metabolism is tightly controlled by dynamic and intricate regulatory mechanisms involving allostery, enzyme abundance and post-translational modifications. The study of the molecular entities involved in these complex mechanisms has been boosted by the advent of high-throughput technologies. The so-called omics enable the quantification of the different molecular entities at different system layers, connecting the genotype with the phenotype. Therefore, the study of the overall behavior of a metabolic network and the omics data integration and analysis must be approached from a holistic perspective. Due to the close relationship between metabolism and cellular phenotype, metabolic modelling has emerged as a valuable tool to decipher the underlying mechanisms governing cell phenotype. Constraint-based modelling and kinetic modelling are among the most widely used methods to study cell metabolism at different scales, ranging from cells to tissues and organisms. These approaches enable integrating metabolomic data, among others, to enhance model predictive capabilities. In this review, we describe the current state of the art in metabolic modelling and discuss future perspectives and current challenges in the field.

scholarly journals Correlation-Based Network Generation, Visualization, and Analysis as a Powerful Tool in Biological Studies: A Case Study in Cancer Cell Metabolism

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Albert Batushansky ◽  
David Toubiana ◽  
Aaron Fait
Keyword(s):  
Metabolic Networks ◽  
Cell Metabolism ◽  
Data Sets ◽  
Metabolomics Data ◽  
Network Generation ◽  
Carcinoma Cell Lines ◽  
Biological Studies ◽  
Metabolic Interactions ◽  
Cancer Cell Metabolism ◽  
Breast Carcinoma Cell Lines

In the last decade vast data sets are being generated in biological and medical studies. The challenge lies in their summary, complexity reduction, and interpretation. Correlation-based networks and graph-theory based properties of this type of networks can be successfully used during this process. However, the procedure has its pitfalls and requires specific knowledge that often lays beyond classical biology and includes many computational tools and software. Here we introduce one of a series of methods for correlation-based network generation and analysis using freely available software. The pipeline allows the user to control each step of the network generation and provides flexibility in selection of correlation methods and thresholds. The pipeline was implemented on published metabolomics data of a population of human breast carcinoma cell lines MDA-MB-231 under two conditions: normal and hypoxia. The analysis revealed significant differences between the metabolic networks in response to the tested conditions. The network under hypoxia had 1.7 times more significant correlations between metabolites, compared to normal conditions. Unique metabolic interactions were identified which could lead to the identification of improved markers or aid in elucidating the mechanism of regulation between distantly related metabolites induced by the cancer growth.

scholarly journals Modelling Cell Metabolism: A Review on Constraint-Based Steady-State and Kinetic Approaches

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 322
Author(s):  
Mohammadreza Yasemi ◽  
Mario Jolicoeur
Keyword(s):  
Parameter Estimation ◽  
Steady State ◽  
Mathematical Modelling ◽  
Kinetic Models ◽  
Metabolic Pathways ◽  
Metabolic Networks ◽  
Cell Metabolism ◽  
Experimental Conditions ◽  
Metabolic Modelling ◽  
Modelling Approaches

Studying cell metabolism serves a plethora of objectives such as the enhancement of bioprocess performance, and advancement in the understanding of cell biology, of drug target discovery, and in metabolic therapy. Remarkable successes in these fields emerged from heuristics approaches, for instance, with the introduction of effective strategies for genetic modifications, drug developments and optimization of bioprocess management. However, heuristics approaches have showed significant shortcomings, such as to describe regulation of metabolic pathways and to extrapolate experimental conditions. In the specific case of bioprocess management, such shortcomings limit their capacity to increase product quality, while maintaining desirable productivity and reproducibility levels. For instance, since heuristics approaches are not capable of prediction of the cellular functions under varying experimental conditions, they may lead to sub-optimal processes. Also, such approaches used for bioprocess control often fail in regulating a process under unexpected variations of external conditions. Therefore, methodologies inspired by the systematic mathematical formulation of cell metabolism have been used to address such drawbacks and achieve robust reproducible results. Mathematical modelling approaches are effective for both the characterization of the cell physiology, and the estimation of metabolic pathways utilization, thus allowing to characterize a cell population metabolic behavior. In this article, we present a review on methodology used and promising mathematical modelling approaches, focusing primarily to investigate metabolic events and regulation. Proceeding from a topological representation of the metabolic networks, we first present the metabolic modelling approaches that investigate cell metabolism at steady state, complying to the constraints imposed by mass conservation law and thermodynamics of reactions reversibility. Constraint-based models (CBMs) are reviewed highlighting the set of assumed optimality functions for reaction pathways. We explore models simulating cell growth dynamics, by expanding flux balance models developed at steady state. Then, discussing a change of metabolic modelling paradigm, we describe dynamic kinetic models that are based on the mathematical representation of the mechanistic description of nonlinear enzyme activities. In such approaches metabolic pathway regulations are considered explicitly as a function of the activity of other components of metabolic networks and possibly far from the metabolic steady state. We have also assessed the significance of metabolic model parameterization in kinetic models, summarizing a standard parameter estimation procedure frequently employed in kinetic metabolic modelling literature. Finally, some optimization practices used for the parameter estimation are reviewed.

scholarly journals Biophysical characterization of melanoma cell phenotype markers during metastatic progression

2021 ◽  
Author(s):  
Anna Sobiepanek ◽  
Alessio Paone ◽  
Francesca Cutruzzolà ◽  
Tomasz Kobiela
Keyword(s):  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Structural Features ◽  
Protein Glycosylation ◽  
Cell Phenotype ◽  
Metastatic Progression ◽  
Label Free ◽  
Serine Threonine Kinase ◽  
Biophysical Characterization ◽  
Viscoelastic Parameters

AbstractMelanoma is the most fatal form of skin cancer, with increasing prevalence worldwide. The most common melanoma genetic driver is mutation of the proto-oncogene serine/threonine kinase BRAF; thus, the inhibition of its MAP kinase pathway by specific inhibitors is a commonly applied therapy. However, many patients are resistant, or develop resistance to this type of monotherapy, and therefore combined therapies which target other signaling pathways through various molecular mechanisms are required. A possible strategy may involve targeting cellular energy metabolism, which has been recognized as crucial for cancer development and progression and which connects through glycolysis to cell surface glycan biosynthetic pathways. Protein glycosylation is a hallmark of more than 50% of the human proteome and it has been recognized that altered glycosylation occurs during the metastatic progression of melanoma cells which, in turn facilitates their migration. This review provides a description of recent advances in the search for factors able to remodel cell metabolism between glycolysis and oxidative phosphorylation, and of changes in specific markers and in the biophysical properties of cells during melanoma development from a nevus to metastasis. This development is accompanied by changes in the expression of surface glycans, with corresponding changes in ligand-receptor affinity, giving rise to structural features and viscoelastic parameters particularly well suited to study by label-free biophysical methods.

scholarly journals The Impact of Exercise Serum on Selected Parameters of CD4+ T Cell Metabolism

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 119-131
Author(s):  
Jana Palmowski ◽  
Kristina Gebhardt ◽  
Thomas Reichel ◽  
Torsten Frech ◽  
Robert Ringseis ◽  
...  
Keyword(s):  
T Cells ◽  
Oxygen Consumption ◽  
T Cell ◽  
Real Time ◽  
Cd4 T Cells ◽  
Cell Metabolism ◽  
Cd4 T Cell ◽  
Autologous Serum ◽  
Cell Phenotype ◽  
The Impact

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.

scholarly journals A method for estimation of elasticities in metabolic networks using steady state and dynamic metabolomics data and linlog kinetics

2006 ◽  
Vol 7 (1) ◽  
Author(s):  
I Emrah Nikerel ◽  
Wouter A van Winden ◽  
Walter M van Gulik ◽  
Joseph J Heijnen
Keyword(s):  
Steady State ◽  
Metabolic Networks ◽  
Metabolomics Data

scholarly journals Reconstruction of Metabolic Networks from High-Throughput Metabolite Profiling Data: In Silico Analysis of Red Blood Cell Metabolism

2007 ◽  
Vol 1115 (1) ◽  
pp. 102-115 ◽  
Author(s):  
I. NEMENMAN ◽  
G. S. ESCOLA ◽  
W. S. HLAVACEK ◽  
P. J. UNKEFER ◽  
C. J. UNKEFER ◽  
...  
Keyword(s):  
Blood Cell ◽  
High Throughput ◽  
Red Blood Cell ◽  
In Silico ◽  
Metabolite Profiling ◽  
Metabolic Networks ◽  
Cell Metabolism ◽  
In Silico Analysis ◽  
Silico Analysis

scholarly journals Hypertension and cognitive disorders: causes and underlying mechanisms

2018 ◽  
Vol 24 (5) ◽  
pp. 496-507
Author(s):  
V. A. Tsyrlin ◽  
N. V. Kuzmenko ◽  
N. G. Pliss
Keyword(s):  
Blood Pressure ◽  
Vascular Dementia ◽  
Memory Impairment ◽  
Cognitive Disorders ◽  
Learning Ability ◽  
Emotional Control ◽  
Brain Pathology ◽  
Personal Opinion ◽  
Close Relationship ◽  
Underlying Mechanisms

Arterial hypertension (HTN) is associated with significant changes in the structure of cerebral vessels. There is a close relationship between the functional activity of neurons and the intensity of their blood supply. Vascular dementia is a heterogeneous group of diseases resulting from the pathology of neurons, glia and vessels. Cognitive disorders are the most typical manifestations of brain pathology in vascular dementia and include memory impairment, decreased learning ability, lack of personal opinion, violation of emotional control and social behavior. The article overviews the data on the organization of cerebral circulation and the mechanisms of its changes in HTN. The article analyzes the causes leading to brain hypoperfusion in elevated blood pressure. The authors discuss the mechanisms resulting in cognitive disorders in hypertensive subjects. We also address the question arising in relation of HTN and cognitive impairments: “To which extent blood pressure should be lowered in hypertensive patients with cognitive decline?”.

scholarly journals Inflammasome- and gasdermin D-independent IL-1β production mobilizes neutrophils to inhibit antitumor immunity

2020 ◽  
Author(s):  
Máté Kiss ◽  
Lieselotte Vande Walle ◽  
Els Lebegge ◽  
Helena Van Damme ◽  
Aleksandar Murgaski ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Antitumor Immunity ◽  
Cytotoxic T Cells ◽  
Antiangiogenic Therapy ◽  
Cell Phenotype ◽  
Inflammasome Activation ◽  
Mouse Tumor ◽  
Neutrophil Accumulation ◽  
Underlying Mechanisms ◽  
Immunosuppressive Microenvironment

ABSTRACTInterleukin-1β (IL-1β) is a central mediator of inflammation whose secretion typically requires proteolytic maturation by the inflammasome and formation of membrane pores by gasdermin D (GSDMD). Emerging evidence suggests an important role for IL-1β in promoting cancer progression in patients, but the underlying mechanisms are little understood. Here, we show a key role for IL-1β in driving tumor progression in two distinct mouse tumor models. Notably, inflammasome activation and GSDMD were dispensable for the production of intratumoral bioactive IL-1β, which promoted systemic mobilization and infiltration of neutrophils into tumors. Neutrophils recruited via IL-1β suppressed the acquisition of an effector T-cell phenotype and subsequent antitumor immune response. Moreover, IL-1β was essential for neutrophil accumulation upon antiangiogenic therapy, thereby contributing to therapy-induced immunosuppression. Antitumor immunity in the absence of IL-1β-dependent neutrophil recruitment relied on immunostimulatory macrophages which promoted the infiltration and activation of cytotoxic T-cells. Overall, these results support a tumor-promoting role for IL-1β through establishing an immunosuppressive microenvironment and show that inflammasome activation is not essential for its release in tumors.

scholarly journals Exofocal changes in experimental focal cerebral ischemia: an experimental approach and its clinical correlation.

1969 ◽  
Vol 39 (3 Supl 3) ◽  
pp. 85-94
Author(s):  
César A. Arango Dávila ◽  
Martha Isabel Escobar ◽  
Efraín Buriticá ◽  
Hernán Pimienta
Keyword(s):  
Focal Cerebral Ischemia ◽  
Cell Metabolism ◽  
Brain Lesion ◽  
Dynamic Structure ◽  
Experimental Models ◽  
Clinical Aspects ◽  
Cell Phenotype ◽  
Cellular Events ◽  
Clinical Observations ◽  
Genes Expression

Introduction: The brain is an extraordinarily dynamic structure specially its physiology in response to pathological events. This response include several mechanisms such as changes in cell metabolism, genes expression and possible modifications in cell phenotype and in connectivity that reflect activation of processes like neurogenesis, neuritogenesis and synaptogenesis. Several aspects related with neuroplasticity has been proposed as part of the pathophysiological bases to understand brain ischemia and its exofocal phenomena. Progress in understanding of the pathophysiology of brain lesion has required the use of experimental models to evaluate cellular events that occur immediately after the lesion or later, to associate this changes with clinical observations and to propose pharmacological neuroprotection therapies. Objective: The purpose of the present work is to compile the advances in understanding of plasticity after brain lesion, mainly related with exofocal areas to a core lesion. Discussion and conclusions: The present work shows recent advances in neuroplasticity based on experimental approaches, and preclinical findings related with the exofocal ischemic phenomena: changes in areas not completely ischemic, changes in no ischemic areas affected by chemical or electrical signals, changes in the pattern of connectivity and adaptative changes in remote areas to the ischemic core. Finally, we discuss clinical aspects associated with this changes, experimental strategies and clinical pharmacological interventions.

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