The Application of Mass Spectrometry to Proteomics and Metabolomics in Biomarker Discovery and Drug Development

Mikami, Takeshi; Aoki, Mikio; Kimura, T.

doi:10.2174/1874-470211205020301

Cited by 20 publications

(26 citation statements)

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“…To do this, we plan to use a combined approach of advanced, high-resolution microscopic imaging and metabolomics. Metabolomics should provide an effective way of establishing which biochemical pathways in H. contortus are affected by individual compounds, and will be highly complementary to transcriptomic and proteomic analyses (reviewed by Mikami et al 2012;Vincent and Barrett 2015). Our goal is to study individual phenotypes of various developmental stages of the parasites during treatment with particular drug candidates (different dosages and time points), and quantitatively assess their metabolic profiles compared with untreated controls, which will enable us to verify that chemical knock-down relates specifically to particular pathways or metabolic chokepoints inferred from the druggable genome (cf.…”

Section: Proposed Hit-to-lead Phasementioning

confidence: 99%

A perspective on genomic-guided anthelmintic discovery and repurposing using Haemonchus contortus

Preston

Jabbar

Gasser

2016

Infection, Genetics and Evolution

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Section: Proposed Hit-to-lead Phasementioning

confidence: 99%

A perspective on genomic-guided anthelmintic discovery and repurposing using Haemonchus contortus

Preston

Jabbar

Gasser

2016

Infection, Genetics and Evolution

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“…Biomarker discovery is a key application in metabolomics that aims to improve disease diagnosis and prognosis while also assessing therapeutic efficacy and toxicity [1][2][3][4]. Metabolomics studies flow sequentially from untargeted to targeted platforms [5][6][7]. Unlike screening in the untargeted approach, targeted quantification of preselected metabolites requires a robust methodology usually with multiple reaction monitoring (MRM) acquisition [6,8,5,7].…”

Section: Introductionmentioning

confidence: 99%

“…Metabolomics studies flow sequentially from untargeted to targeted platforms [5][6][7]. Unlike screening in the untargeted approach, targeted quantification of preselected metabolites requires a robust methodology usually with multiple reaction monitoring (MRM) acquisition [6,8,5,7]. Targeted analysis is typically conducted by coupling tandem mass spectrometry (MS/MS) to gas chromatography (GC) or liquid chromatography (LC) [6,8,5,7].…”

Section: Introductionmentioning

confidence: 99%

Comparison of accuracy and precision between multipoint calibration, single point calibration, and relative quantification for targeted metabolomic analysis

et al. 2018

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Targeted metabolomics requires accurate and precise quantification of candidate biomarkers, often through tandem mass spectrometric (MS/MS) analysis. Differential isotope labeling (DIL) improves mass spectrometric (MS) analysis in metabolomics by derivatizing metabolites with two isotopic forms of the same reagent. Despite its advantages, DIL-liquid chromatographic (LC)-MS/MS can result in substantial increase in workload when fully validated quantitative methods are required. To decrease the workload, we hypothesized that single point calibration or relative quantification could be used as alternative methods. Either approach will result in significant saving in resources and time. To test our hypothesis, six urinary metabolites were selected as model compounds. Urine samples were analyzed using a fully validated multipoint dansyl chloride-DIL-LC-MS/MS method. Samples were reprocessed using single point calibration and relative quantification modes. Our results demonstrated that the performance of single point calibration or relative quantification was inferior, for some metabolites, to multipoint calibration. The lower limit of quantification failed in the quantification of ethanolamine in most of participant samples using single point calibration. In addition, its precision was not acceptable in one participant during serine and ethanolamine quantification. On the other hand, relative quantification resulted in the least accurate data. In fact, none of the data generated from relative quantification for serine was comparable to that obtained from multipoint calibration. Finally, while single point calibration showed an overall acceptable performance for the majority of the model compounds, we cannot extrapolate the findings to other metabolites within the same analytical run. Analysts are advised to assess accuracy and precision for each metabolite in which single point calibration is the intended quantification mean.

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“…Pseudotargeted metabolomics method integrates advantages of non-targeted and targeted method, which had good stability, wide linear range, high sensitivity, simple dataset and wide coverage [26,32,33]. MS-based hyphenated techniques [35][36][37] have become powerful tools for metabolomics. LC-MS/MS is highly sensitive and wide coverage of metabolome, which is suitable for the detection of majority metabolites, especially secondary metabolites in plant [38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Sample‐directed pseudotargeted method for the metabolic profiling analysis of rice seeds based on liquid chromatography with mass spectrometry

Zhang

Zhao

Zeng

et al. 2015

J of Separation Science

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Rice is one of the most important food crops in the world. Metabolite composition in rice seeds varies significantly depending on genetic variety, climatic alternation and agricultural practice. Metabolomics is a powerful tool to reveal the metabolic response of rice to various conditions. In this work, a rice seed sample-directed pseudotargeted metabolomics method was first established and validated based on ultra high performance liquid chromatography with triple quadrupole mass spectrometry in the multiple reaction monitoring mode. A total of 749 and 617 ion pairs in positive and negative modes were achieved, respectively. Among them, about 200 metabolites were identified or tentatively identified. The developed method showed better linearity and repeatability than those of non-targeted metabolomics method. Good intra-day and inter-day precisions, recoveries and wide linear range were also obtained. Furthermore, the method was applied for the investigation of metabolic variation of rice seeds with two wild cultivars and their transgenic lines that were grown in two locations. Principal component analysis indicated that the effects of cultivar and location on metabolic variations were far more than those of gene modification. The nonparametric Mann-Whitney U test revealed that most metabolites were influenced by cultivar, location and gene modifications together.

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The Application of Mass Spectrometry to Proteomics and Metabolomics in Biomarker Discovery and Drug Development

Cited by 20 publications

References 0 publications

A perspective on genomic-guided anthelmintic discovery and repurposing using Haemonchus contortus

A perspective on genomic-guided anthelmintic discovery and repurposing using Haemonchus contortus

Comparison of accuracy and precision between multipoint calibration, single point calibration, and relative quantification for targeted metabolomic analysis

Sample‐directed pseudotargeted method for the metabolic profiling analysis of rice seeds based on liquid chromatography with mass spectrometry

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