Human Systems Biology and Metabolic Modelling: A Review—From Disease Metabolism to Precision Medicine

Angione, Claudio

doi:10.1155/2019/8304260

Cited by 70 publications

(51 citation statements)

References 194 publications

(198 reference statements)

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“…Metabolic pathways are interconnected and metabolic phenotypes involve multiple organs. The exact mechanisms underlying the onset and progression of metabolism related disorders are still unclear (25). In the HPA study, tissue specific metabolic maps were reconstructed by integrating RNA-seq data from 32 different tissues and protein compartment information from an antibody map.…”

Section: Metabolismmentioning

confidence: 99%

A Quantitative Proteome Map of the Human Body

Jiang

Wang

Lin

et al. 2019

Preprint

109

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Quantitative proteome study of 32 human tissues and integrated analysis with transcriptome data revealed that understanding protein levels could provide in-depth knowledge to post transcriptional or translational regulations, human metabolism, secretome, and diseases. AbstractDetermining protein levels in each tissue and how they compare with RNA levels is important for understanding human biology and disease as well as regulatory processes that control protein levels. We quantified the relative protein levels from 12,627 genes across 32 normal human tissue types prepared by the GTEx project. Known and new tissue specific or enriched proteins (5,499) were identified and compared to transcriptome data. Many ubiquitous transcripts are found to encode highly tissue specific proteins. Discordance in the sites of RNA expression and protein detection also revealed potential sites of synthesis and action of protein signaling molecules. Overall, these results provide an extraordinary resource, and demonstrate that understanding protein levels can provide insights into metabolism, regulation, secretome, and human diseases.

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Section: Metabolismmentioning

confidence: 99%

A Quantitative Proteome Map of the Human Body

Jiang

Wang

Lin

et al. 2019

Preprint

109

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“…FBA), a number of questions in metabolic systems biology remain open. In particular, recent evidence suggests that cells adjust their metabolism to optimize multiple (potentially conflicting) objectives and ensure flexible adaptation to changes in their external environments [8], [9]. However, FBA-based methods usually consider the optimization of a single objective (e.g.…”

Section: Introductionmentioning

confidence: 99%

Discovering Essential Multiple Gene Effects Through Large Scale Optimization: An Application to Human Cancer Metabolism

Occhipinti

Hamadi²,

Kugler

et al. 2021

IEEE/ACM Trans. Comput. Biol. and Bioinf.

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Computational modelling of metabolic processes has proven to be a useful approach to formulate our knowledge and improve our understanding of core biochemical systems that are crucial to maintaining cellular functions. Towards understanding the broader role of metabolism on cellular decision-making in health and disease conditions, it is important to integrate the study of metabolism with other core regulatory systems and omics within the cell, including gene expression patterns.After quantitatively integrating gene expression profiles with a genome-scale reconstruction of human metabolism, we propose a set of combinatorial methods to reverse engineer gene expression profiles and to find pairs and higher-order combinations of genetic modifications that simultaneously optimize multiobjective cellular goals. This enables us to suggest classes of transcriptomic profiles that are most suitable to achieve given metabolic phenotypes.We demonstrate how our techniques are able to compute beneficial, neutral or "toxic" combinations of gene expression levels. We test our methods on nine tissue-specific cancer models, comparing our outcomes with the corresponding normal cells, identifying genes as targets for potential therapies. Our methods open the way to a broad class of applications that require an understanding of the interplay among genotype, metabolism, and cellular behaviour, at scale.

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“…Molecular-omics stand at the forefront of future medicine, and multi-omics approaches support the development of systemic molecular diagnosis, preventive medicine, and personalized treatments [ 4 , 5 ]. Metabolomics plays a key role in this translational omics cascade [ 6 , 7 ], and equally strives to address the chemical complexity of our environment.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Approaches to Study Chemical Exposure-Related Metabolism Alterations in Mammalian Cell Cultures

Balcerczyk

Damblon

Elena-Herrmann

et al. 2020

IJMS

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Biological organisms are constantly exposed to an immense repertoire of molecules that cover environmental or food-derived molecules and drugs, triggering a continuous flow of stimuli-dependent adaptations. The diversity of these chemicals as well as their concentrations contribute to the multiplicity of induced effects, including activation, stimulation, or inhibition of physiological processes and toxicity. Metabolism, as the foremost phenotype and manifestation of life, has proven to be immensely sensitive and highly adaptive to chemical stimuli. Therefore, studying the effect of endo- or xenobiotics over cellular metabolism delivers valuable knowledge to apprehend potential cellular activity of individual molecules and evaluate their acute or chronic benefits and toxicity. The development of modern metabolomics technologies such as mass spectrometry or nuclear magnetic resonance spectroscopy now offers unprecedented solutions for the rapid and efficient determination of metabolic profiles of cells and more complex biological systems. Combined with the availability of well-established cell culture techniques, these analytical methods appear perfectly suited to determine the biological activity and estimate the positive and negative effects of chemicals in a variety of cell types and models, even at hardly detectable concentrations. Metabolic phenotypes can be estimated from studying intracellular metabolites at homeostasis in vivo, while in vitro cell cultures provide additional access to metabolites exchanged with growth media. This article discusses analytical solutions available for metabolic phenotyping of cell culture metabolism as well as the general metabolomics workflow suitable for testing the biological activity of molecular compounds. We emphasize how metabolic profiling of cell supernatants and intracellular extracts can deliver valuable and complementary insights for evaluating the effects of xenobiotics on cellular metabolism. We note that the concepts and methods discussed primarily for xenobiotics exposure are widely applicable to drug testing in general, including endobiotics that cover active metabolites, nutrients, peptides and proteins, cytokines, hormones, vitamins, etc.

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Human Systems Biology and Metabolic Modelling: A Review—From Disease Metabolism to Precision Medicine

Cited by 70 publications

References 194 publications

A Quantitative Proteome Map of the Human Body

A Quantitative Proteome Map of the Human Body

Discovering Essential Multiple Gene Effects Through Large Scale Optimization: An Application to Human Cancer Metabolism

Metabolomic Approaches to Study Chemical Exposure-Related Metabolism Alterations in Mammalian Cell Cultures

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