Systematic functional analysis of the yeast genome

Oliver, Stephen G.; Winson, Michael K.; Kell, Douglas B.; Baganz, Frank

doi:10.1016/s0167-7799(98)01214-1

Cited by 1,081 publications

(558 citation statements)

References 31 publications

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“…The complete array of small-molecule metabolites that are found within a biological system constitutes the metabolome and reflects the functional phenotype [20]. Metabolomics, is the systematic study of this dynamic inventory of metabolites, as small molecular biomarkers representing the functional phenotype in a biological system (see [16] for review).…”

Section: Introductionmentioning

confidence: 99%

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome

Seli

Bruce

Botros³

et al. 2010

J Assist Reprod Genet

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Purpose Assessment of embryo viability is a key component of in vitro fertilization (IVF) and currently relies largely on embryo morphology and cleavage rate. In this study, we used receiver operating characteristic (ROC) analysis to compare the Viability Score (generated by metabolomic profiling of spent embryo culture media using near infrared (NIR) spectroscopy) to morphologic grading for predicting pregnancy in women undergoing single embryo transfer (SET) on day 5. Methods A total of 198 spent embryo culture media samples were collected in four IVF centers located in the USA, Europe and Australia. First, 137 samples (training set) were analyzed by NIR to develop an algorithm that generates a Viability Score predictive of pregnancy for each sample. Next, 61 samples (validation set) were analyzed by observers blinded to embryo morphology and IVF outcome, using the Day 5 algorithm generated with the training set. Pregnancy was defined as fetal cardiac activity (FCA) at 12 weeks of gestation. Genet (2011) 28:137-144 DOI 10.1007 potential to be a better classifier for pregnancy outcome than morphology alone in women undergoing SET on day 5.

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Section: Introductionmentioning

confidence: 99%

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome

Seli

Bruce

Botros³

et al. 2010

J Assist Reprod Genet

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“…METABOLOME: The full set of metabolites within, or that can be secreted from, a biological system such as a cell type or tissue. [99] METABONOME: The sum of the cellular metabolomes in a multi-cellular organism and their interaction components plus the products of chemical transformations and extra-genomically generated metabolites. [100] METABOTYPE: The metabolic phenotype of an organism.…”

Section: Metabolomicsmentioning

confidence: 99%

NMR-based pharmacometabonomics: A new paradigm for personalised or precision medicine

Everett

2017

Progress in Nuclear Magnetic Resonance Spectroscopy

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Metabolic profiling by NMR spectroscopy or hyphenated mass spectrometry, known as metabonomics or metabolomics, is an important tool for systemsbased approaches in biology and medicine. The experiments are typically done in a diagnostic fashion where changes in metabolite profiles are interpreted as a consequence of an intervention or event; be that a change in diet, the administration of a drug, physical exertion or the onset of a disease. By contrast, pharmacometabonomics takes a prognostic approach to metabolic profiling, in order to predict the effects of drug dosing before it occurs. Differences in predose metabolite profiles between groups of subjects are used to predict postdose differences in response to drug administration. Thus the paradigm is inverted and pharmacometabonomics is the metabolic equivalent of pharmacogenomics. Although the field is still in its infancy, it is expected that pharmacometabonomics, alongside pharmacogenomics, will assist with the delivery of personalised or precision medicine to patients, which is a critical goal of 21 st century healthcare. Highlights metabonomics or metabolomics involves metabolic profiling by NMR or MS methods  metabonomics is used in a diagnostic mode to study the effects of an intervention  pharmacometabonomics is a prognostic method to predict the effects of drugs  pharmacometabonomics is a special case of predictive metabonomics  pharmacometabonomics will help to deliver personalised medicine in the future Graphical AbstractNMR-Based Pharmacometabonomics PNMRS 2017

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“…Metabolomics seeks to measure the concentrations of nominally all of the [small molecular weight (MW)] metabolites in a particular system, for example, a body fluid such as serum or an ensemble of cells [17,37,38], although normally a more restricted subset, the 'metabolic profile' is measured in practice. This is because of the huge chemical diversity, especially in terms of polarity, among different metabolites.…”

Section: Metabolomics and Technologies For Its Measurementmentioning

confidence: 99%

“…An attraction of the metabolome has always been that it is numerically smaller, and thus more tractable, than the transcriptome or proteome [37]. In the case of baker's yeast (Saccharomyces cerevisiae), the latest models (e.g.…”

Section: Sizes Of the Human And Other Metabolomesmentioning

confidence: 99%

Systems biology, metabolic modelling and metabolomics in drug discovery and development

Kell

2006

Drug Discovery Today

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Unlike signalling pathways, metabolic networks are subject to strict stoichiometric constraints. Metabolomics amplifies changes in the proteome, and represents more closely the phenotype of an organism. Recent advances enable the production (and computer-readable encoding as SBML) of metabolic network models reconstructed from genome sequences, as well as experimental measurements of much of the metabolome. There is increasing convergence between the number of human metabolites estimated via genomics ( 3000) and the number measured experimentally. It is thus both timely, and now possible, to bring these two approaches together as an integrated (if distributed) whole to help understand the genesis of metabolic biomarkers, the progress of disease, and the modes of action, efficacy, off-target effects and toxicity of pharmaceutical drugs. Systems biology and metabolic modelling in the 21st CenturyAlthough there are many individual definitions, most commentators (including this one [1,2]) take it that systems biology involves an iterative interplay between more or less high-throughput and high-content 'wet' experiments, technology development, theory and computational modelling, and that it is the involvement of computational modelling, in particular, in the process that sets systems biology apart from the more traditional and more reductionist molecular biology. Metabolomics illustrates this amply. There is also the view that the perceived decrease in the effectiveness of the target-based drug discovery process [3][4][5], including the still-high levels of attrition [6], means that we must move towards understanding organisms at something more akin to a whole-system level [7][8][9][10][11].The question then arises as to what part of a system one might first beneficially model? Although there has, unsurprisingly, been considerable interest in modelling the major signalling pathways (e.g. Refs [12,13]), there are several reasons why it is timely to turn our attention to the level of small molecule metabolism, which is the focus of this review. Metabolism is more discriminatingIt has long been known, and proven through the formalism of metabolic control analysis [7,10,[14][15][16], that whereas small changes in the concentrations of enzymes (and the transcripts that encode them) have only small effects on the fluxes through metabolic pathways, they have substantial effects on the concentrations of metabolic intermediates. Because the metabolome (nominally the concentrations of 'all' the metabolites measured in a system of interest [17]) is downstream of the proteome, it is thereby 'amplified' both in theory [18] and in practice [19,20] and represents a more sensitive level of organisation than do the macromolecular 'omes for understanding a complex biological system, and the changes in it that might be occasioned by disease or pharmaceutical intervention [21,22]. Metabolic reconstruction is now mature and timelyAn attractive feature for the purposes of modelling is that metabolism, in contrast to signalling pathways, ...

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Systematic functional analysis of the yeast genome

Cited by 1,081 publications

References 31 publications

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome

NMR-based pharmacometabonomics: A new paradigm for personalised or precision medicine

Systems biology, metabolic modelling and metabolomics in drug discovery and development

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