Do not just do it, do it right: urinary metabolomics –establishing clinically relevant baselines

Trivedi, Drupad K.; Iles, Ray K.

doi:10.1002/bmc.3219

Cited by 23 publications

(14 citation statements)

References 124 publications

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“…While many analytical tools can be used for the identification and quantification of urine metabolites, mass spectrometry, especially when linked to a suitable separation technique, can serve as an ideal platform for metabolomics research (Dunn et al, 2013;Armitage & Barbas, 2014;Trivedi & Iles, 2014a;Zhang et al, 2012a). MS offers the preferred sensitivity, high throughput capability and the desired quantitative outputs, absolute or relative.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometric based approaches in urine metabolomics and biomarker discovery

Khamis

Adamko

El‐Aneed

2015

Mass Spectrometry Reviews

246

177

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Urine metabolomics has recently emerged as a prominent field for the discovery of non-invasive biomarkers that can detect subtle metabolic discrepancies in response to a specific disease or therapeutic intervention. Urine, compared to other biofluids, is characterized by its ease of collection, richness in metabolites and its ability to reflect imbalances of all biochemical pathways within the body. Following urine collection for metabolomic analysis, samples must be immediately frozen to quench any biogenic and/or non-biogenic chemical reactions. According to the aim of the experiment; sample preparation can vary from simple procedures such as filtration to more specific extraction protocols such as liquid-liquid extraction. Due to the lack of comprehensive studies on urine metabolome stability, higher storage temperatures (i.e. 4 °C) and repetitive freeze-thaw cycles should be avoided. To date, among all analytical techniques, mass spectrometry (MS) provides the best sensitivity, selectivity and identification capabilities to analyze the majority of the metabolite composition in the urine. Combined with the qualitative and quantitative capabilities of MS, and due to the continuous improvements in its This is the peer reviewed version of: Khamis, M. M., Adamko, D. J. and El-Aneed, A. (2015), Mass Spec Rev., published in final form at https://doi.org/10.1002/mas.21455. [HILIC]), liquid chromatography (LC)-MS is unequivocally the most utilized and the most informative analytical tool employed in urine metabolomics. Furthermore, differential isotope tagging techniques has provided a solution to ion suppression from urine matrix thus allowing for quantitative analysis. In addition to LC-MS, other MS-based technologies have been utilized in urine metabolomics. These include direct injection (infusion)-MS, capillary electrophoresis-MS and gas chromatography-MS. In this article, the current progresses of different MS-based techniques in exploring the urine metabolome as well as the recent findings in providing potentially diagnostic urinary biomarkers are discussed.

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Section: Discussionmentioning

confidence: 99%

Mass spectrometric based approaches in urine metabolomics and biomarker discovery

Khamis

Adamko

El‐Aneed

2015

Mass Spectrometry Reviews

246

177

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“…Numerous methods of urinary metabolomic profiling have been widely reported in order to ascertain changes in human metabolism owing to drug or disease processes (Trivedi and Iles, ). However, during pregnancy there are dramatic metabolic changes which are due to the establishment and growth of the fetus and maternal adaptation to the fetus (Lain and Catalano, ; Abduljalil et al ., ).…”

Section: Introductionmentioning

confidence: 99%

HILIC‐MS‐based shotgun metabolomic profiling of maternal urine at 9–23 weeks of gestation – establishing the baseline changes in the maternal metabolome

Trivedi

Iles

2014

Biomedical Chromatography

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In this data-rich age it is no longer necessary to methodically isolate, characterize and measure specific molecules. What is important is to identify which of the hundreds or thousands of resolved and measured 'unknown' molecules are potentially associated with the pathophysiology of interest. We have taken LC-MS data from pregnancy urine and applied SIMCA P+ data analysis software in shotgun metabolomics to search the large amount of data for significant metabolite changes that occur in the transition from the first to early second trimester of pregnancy. Seventy-two individual urine samples were examined spanning 9-23 weeks of gestation. Three-hundred and eighty-three ions were identified and variations were mapped between profiles of different gestational age and the significance quantified. In urine collected during pregnancy, the transition from first to early second trimester revealed a relatively steady pattern of metabolites except for four that showed a dramatic fall in abundance as pregnancy progressed from the first to second trimester. The pattern of changes in urinary metabolites identified by Zwitterionic Hydrophilic Liquid Interaction Chromatography (ZIC-HILIC) coupled to mass spectrometry was evaluated and we established a baseline of changes from which a search for metabolomic markers associated with clinical pathologies of pregnancy can be made as a part of wider ultraomics study.

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“…This gestational age and mathematical correction required in our MALDI ToF MS urinary spectra pro iling tests is akin to the multiple of median correction adopted in conventional maternal serum and proposed metabolomics screening tests for Down syndrome [27][28][29][30][31][32]. Thus, an optimized screening https://doi.org/10.29328/journal.apb.1001008 test for Down syndrome pregnancy by maternal urinary MALDI ToF MS analysis will require dating of the pregnancy at sampling so that an appropriate decision algorithm can be applied.…”

Section: Urinary Sc Reening By Maldi Tof Ms In View Of Current Practicesmentioning

confidence: 99%

The importance of gestational age in first trimester, maternal urine MALDI-Tof MS screening tests for Down Syndrome

Iles¹,

Nicolaides²,

Pais³

et al. 2019

Ann Proteom Bioinform

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Background: The proposal that MALDI-ToF mass spectrometry could be used as a direct, rapid and affordable diagnostic tool in clinical laboratory medicine has moved from a theoretical possibility to a reality for Microbiology. Several studies have proposed the application of this technology in obstetric and gynaecological evaluation of patients. In particular, we have proposed that the adoption of MALDI-ToF mass spectrometry in examination of maternal pregnancy urine samples for the detection of Downs syndrome. Methods: A retrospective collection of 20 Down Syndrome and 100 non-aneuploid pregnancy urines at 12 to 14 weeks gestation, collected in 2007-2008 from high risk pregnancy cohorts, were examined by MALDI-ToF mass spectrometry in the mass/charge range between 1000 and 100000 m/z. Normalisation of spectral data was defi ned using mass bins of 100 m/z expressed as a percentage of the total ion count of the mass spectra from 2000 to 11000 m/z. Of the ninety 100 m/z bins, forty-six were identifi ed as m/z bins at which statistically signifi cant differences in spectra occurred between Downs and control/non-aneuploid samples. Based on the differences and variance, for values at these bins, weighted scores of the probability of being Downs were assigned. Comparative algorithms consisting of various mass bins were tested for ability to distinguish Down syndrome from non-aneuploid pregnancy. Results: Although various algorithms could distinguish Downs from non-aneuploid controls, it was found that gestational age was a confounding factor and that if separated into gestational age matched cohorts the ability to distinguish the groups improved dramatically e.g. whilst a 19 bins algorithm separated 100% of Downs from non-aneuploid pregnancies for a 9% false positive rate in the mixed gestational ages group; a two bin algorithm distinguished 100% of Downs for a 6% false positive rate for the 12 weeks gestational age pregnancies. Conclusion: Normalised MALDI-ToF mass spectra, at 2000 to 11000 m/z, of maternal urine gives rise to gestational age specifi c screening tests algorithms for Downs's syndrome. The importance of gestational age in fi rst trimester, maternal urine MALDI-Tof MS screening tests for Down Syndrome

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Do not just do it, do it right: urinary metabolomics –establishing clinically relevant baselines

Cited by 23 publications

References 124 publications

Mass spectrometric based approaches in urine metabolomics and biomarker discovery

Mass spectrometric based approaches in urine metabolomics and biomarker discovery

HILIC‐MS‐based shotgun metabolomic profiling of maternal urine at 9–23 weeks of gestation – establishing the baseline changes in the maternal metabolome

The importance of gestational age in first trimester, maternal urine MALDI-Tof MS screening tests for Down Syndrome

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