Metabolite profiling: from diagnostics to systems biology

Fernie, Alisdair R.; Trethewey, Richard N.; Krotzky, Arno J.; Willmitzer, Lothar

doi:10.1038/nrm1451

Cited by 744 publications

(550 citation statements)

References 50 publications

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“…Metabolomics is recognised as the ultimate “omics” discipline with high potential to identify sensitive and specific markers, and to understand the mechanisms involved in the development of pathological processes [2]. The recent technological revolution in separation and detection of small molecules, combined with rapid progress in bioinformatics, is making possible to rapidly measure a large number of metabolites in a small amount of sample [3,4].…”

Section: Introductionmentioning

confidence: 99%

Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

Clos-García

Loizaga-Iriarte

Zúñiga-García

et al. 2018

J of Extracellular Vesicle

120

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Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultra-high-performance liquid chromatography–mass spectrometry. The correlation between metabolites and clinical parameters was studied, and metabolites with differential abundance in PCa urinary EVs were detected and mapped into cellular pathways. We detected 248 metabolites belonging to different chemical families including amino acids and various lipid species. Among these metabolites, 76 exhibited significant differential abundance between PCa and BPH. Interestingly, urine EVs recapitulated many of the metabolic alterations reported in PCa, including phosphathidylcholines, acyl carnitines, citrate and kynurenine. Importantly, we found elevated levels of the steroid hormone, 3beta-hydroxyandros-5-en-17-one-3-sulphate (dehydroepiandrosterone sulphate) in PCa urinary EVs, in line with the potential elevation of androgen synthesis in this type of cancer. This work supports urinary EVs as a non-invasive source to infer metabolic changes in PCa.

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Section: Introductionmentioning

confidence: 99%

Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

Clos-García

Loizaga-Iriarte

Zúñiga-García

et al. 2018

J of Extracellular Vesicle

120

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“…1 For practical applications, the sample volume should be as small as possible. 2 For example, glucose sensors have revolutionized the health care of diabetic patients;…”

Section: Introductionmentioning

confidence: 99%

Flow Cytometry-Assisted Detection of Adenosine in Serum with an Immobilized Aptamer Sensor

Huang

Liu

2010

Anal. Chem.

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Aptamers are single-stranded nucleic acids that can selectively bind to essentially any molecule of choice. Because of their high stability, low cost, ease of modification and availability through selection, aptamers hold great promise in addressing key challenges in bioanalytical chemistry. In the past fifteen years many highly sensitive fluorescent aptamer sensors have been reported. However, few such sensors showed high performance in serum samples. Further challenges related to practical applications include detection in a very small sample volume and a low dependence of sensor performance on ionic strength.We report the immobilization of an aptamer sensor on a magnetic microparticle and the use of flow cytometry for detection. Flow cytometry allows the detection of individual particles in a capillary and can effectively reduce the light scattering effect of serum. Since DNA immobilization generated a highly negatively charged surface and caused an enrichment of counter ions, the sensor performance showed a lower salt dependence. The detection limits for adenosine are determined to be 178 and 167 M in buffer and in 30% serum, respectively. Finally, we demonstrated that the detection can be carried out in 10 L of 90% human blood serum.3

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“…This large expansion in chemical complexity lies at the center of the flexibility and complexity of biological systems, as it allows different proteins to perform an enormous range of different functions. Nevertheless, proteins still have a simple primary structure, with amino acids linked via a peptide bond in a fixed sequence that, via the universal genetic code, can be unambiguously linked to the sequence of nucleic acids (Aebersold and Mann, 2003;Fernie et al, 2004;Baerenfaller et al, 2008). This logic breaks down when we consider entities that are generated by the activities of individual proteins or sets of proteins, like metabolites.…”

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confidence: 99%

On the Discordance of Metabolomics with Proteomics and Transcriptomics: Coping with Increasing Complexity in Logic, Chemistry, and Network Interactions Scientific Correspondence

2012

Self Cite

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We suspect that many biologists who have been following the development of functional 'omics and systems biology are wondering why, compared with the success in integrating information from large-scale studies of transcripts and, more recently, proteins, there is less success in integrating information about metabolism.Information about thousands of transcripts has been integrated into large databases that are used by thousands of scientists (Zimmermann et al., 2004). Rapid advances will soon allow a similar approach in quantitative proteomics. Strategies also exist to integrate information about the expression of genes, as transcripts, with information about changes in the levels of the encoded proteins. Even when changes in transcript levels do not lead to changes in the levels of the encoded proteins, this apparent discrepancy can often be explained by quantitative analysis of the data sets and information about translational regulation and protein turnover (Piques et al., 2009; Schwanhäusser et al., 2011). Such advances are providing systemslevel information about transcriptional and signaling networks that regulate the transcript and protein abundance. However, another important goal of systems biology is a comprehensive understanding of the functional importance of these changes in transcript and protein abundance. Although there is sometimes an encouragingly simple relationship between changes of transcripts and proteins and changes in downstream biological functions, quite often there is a major discordance. In this scientific correspondence, we will discuss reasons for this apparent disconnect, which lie partly in technical issues and partly in the complexity and structure of metabolic networks, and then propose some priorities in metabolic research to combat these problems.As we climb up what has been described as the "pyramid of life" (Barabási and Oltvai, 2004) from gene through RNA and protein to phenotype (which includes chemical composition), we are confronted with an increasing complexity both at the chemical level and in the logic that is needed to draw inferences from one level to the next. Nucleic acids consist of four bases, joined by the same phosphoester bond and with pairwise interacting side chains. This simple structure allows a near-to-binary storage and transmission of information. Proteins are chemically much more complex, due to the functionalities of 20 different amino acid side chains. This large expansion in chemical complexity lies at the center of the flexibility and complexity of biological systems, as it allows different proteins to perform an enormous range of different functions. Nevertheless, proteins still have a simple primary structure, with amino acids linked via a peptide bond in a fixed sequence that, via the universal genetic code, can be unambiguously linked to the sequence of nucleic acids (Aebersold and Mann, 2003;Fernie et al., 2004; Baerenfaller et al., 2008). This logic breaks down when we consider entities that are generated by the activities of individual pr...

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Metabolite profiling: from diagnostics to systems biology

Cited by 744 publications

References 50 publications

Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

Flow Cytometry-Assisted Detection of Adenosine in Serum with an Immobilized Aptamer Sensor

On the Discordance of Metabolomics with Proteomics and Transcriptomics: Coping with Increasing Complexity in Logic, Chemistry, and Network Interactions Scientific Correspondence

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