The emergence of metabolomics as a key discipline in the drug discovery process

Fillet, Marianne; Frédérich, Michel

doi:10.1016/j.ddtec.2015.01.006

Cited by 39 publications

(36 citation statements)

References 35 publications

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“…4 Metabolomics applies analytical chemistry techniques such as nuclear magnetic resonance (NMR) spectroscopy or hyphenated mass spectrometry combined with advanced computational and informatics methods to analyse low molecular weight compounds in a biological sample. [5][6][7] It has previously been applied to milk in relation to physiology and composition. [8][9][10][11][12] There have also been investigations of mastitis using Gas Chromatography-Mass Spectrometry (GC-MS) and NMR spectroscopy based metabolomics approaches.…”

Section: Introductionmentioning

confidence: 99%

Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 3. Untargeted metabolomics

et al. 2016

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Intramammary infection leading to bovine mastitis is the leading disease problem affecting dairy cows and has marked effects on the milk produced by infected udder quarters. An experimental model of Streptococcus uberis mastitis has previously been investigated for clinical, immunological and pathophysiological alteration in milk, and has been the subject of peptidomic and quantitative proteomic investigation. The same sample set has now been investigated with a metabolomics approach using liquid chromatography and mass spectrometry. The analysis revealed over 3000 chromatographic peaks, of which 690 were putatively annotated with a metabolite. Hierarchical clustering analysis and principal component analysis demonstrated that metabolite changes due to S. uberis infection were maximal at 81 hours post challenge with metabolites in the milk from the resolution phase at 312 hours post challenge being closest to the pre-challenge samples. Metabolic pathway analysis revealed that the majority of the metabolites mapped to carbohydrate and nucleotide metabolism show a decreasing trend in concentration up to 81 hours post-challenge whereas an increasing trend was found in lipid metabolites and di-, tri- and tetra-peptides up to the same time point. The increase in these peptides coincides with an increase in larger peptides found in the previous peptidomic analysis and is likely to be due to protease degradation of milk proteins. Components of bile acid metabolism, linked to the FXR pathway regulating inflammation, were also increased. Metabolomic analysis of the response in milk during mastitis provides an essential component to the full understanding of the mammary gland's response to infection.

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Section: Introductionmentioning

confidence: 99%

Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 3. Untargeted metabolomics

et al. 2016

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“…Techniques have been further refined in the last 15 years by the utilisation of more sophisticated separation techniques (capillary electrophoresis, liquid chromatography, etc.) and additional detection methods (nuclear magnetic resonance, Fourier transform infrared spectroscopy) [41]. Tens of thousands of metabolites have been identified in humans and are collected in the human metabolome database ().…”

Section: Metabolomics In Drug Discoverymentioning

confidence: 99%

“Omics”-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives

2016

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The pharmaceutical industry faces unsustainable program failure despite significant increases in investment. Dwindling discovery pipelines, rapidly expanding R&D budgets and increasing regulatory control, predict significant gaps in the future drug markets. The cumulative duration of discovery from concept to commercialisation is unacceptably lengthy, and adds to the deepening crisis. Existing animal models predicting clinical translations are simplistic, highly reductionist and, therefore, not fit for purpose. The catastrophic consequences of ever-increasing attrition rates are most likely to be felt in the developing world, where resistance acquisition by killer diseases like malaria, tuberculosis and HIV have paced far ahead of new drug discovery. The coming of age of Omics-based applications makes available a formidable technological resource to further expand our knowledge of the complexities of human disease. The standardisation, analysis and comprehensive collation of the “data-heavy” outputs of these sciences are indeed challenging. A renewed focus on increasing reproducibility by understanding inherent biological, methodological, technical and analytical variables is crucial if reliable and useful inferences with potential for translation are to be achieved. The individual Omics sciences—genomics, transcriptomics, proteomics and metabolomics—have the singular advantage of being complimentary for cross validation, and together could potentially enable a much-needed systems biology perspective of the perturbations underlying disease processes. If current adverse trends are to be reversed, it is imperative that a shift in the R&D focus from speed to quality is achieved. In this review, we discuss the potential implications of recent Omics-based advances for the drug development process.

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“…The determination of metabolites in biological samples is commonly carried out using nuclear magnetic resonance (NMR) and mass spectrometry (MS), combined with chromatography. Due the significantly higher throughput and sensitivity of MS, metabolomics has progressed to numerous targeted semiquantitative and quantitative approaches, now used as routine methods in many fields, such as cell biology [133,134], oncology [135,136], drug discovery [137,138], toxicity studies [139,140], nutrition [141,142] and diagnosis of multiple diseases, namely, diabetes [143], cardiovascular dysfunctions [144] and psychiatric sciences [145]. As all other omics, capable of generating massive amounts of data, the success of metabolomics studies rely on the detailed selection of samples and careful execution of the experimental protocols [146], from sample collection to data acquisition, processing and quality assurance [147].…”

Section: Metabolomicsmentioning

confidence: 99%

Analytical tools to assess aging in humans: The rise of geri-omics

Costa

Rocha-Santos

2016

TrAC Trends in Analytical Chemistry

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Population aged 65+ is expected to be over 2.5 times that of the population aged 0-4 by 2050. The onset of age-related ailments, such as neurodegenerative, cardiovascular and respiratory diseases will lead to unprecedented challenges in the health care systems of all countries affected. Yet, despite the acceptance that aging is a natural process, aging research is very much a maturing science. It is currently focused on understanding the physiological changes that take place in "normal" aging and the molecular multimechanistic process that is at the core of senescence. Contributing factors are not fully understood and omics-, namely, transcriptomics, proteomics and metabolomics-are at the forefront of this research. Herein, we overview some of the most recent works focusing on aging through different omics and related bioinformatic tools and discuss how these can contribute for the elucidation of one of the most baffling aspects of human life.

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The emergence of metabolomics as a key discipline in the drug discovery process

Abstract: Metabolomics is a recent science that could be defined as the comprehensive qualitative and quantitative analysis of all small molecular weight compounds present in a cell,

Cited by 39 publications

References 35 publications

Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 3. Untargeted metabolomics

Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 3. Untargeted metabolomics

“Omics”-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives

Analytical tools to assess aging in humans: The rise of geri-omics

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