Inter-Laboratory Comparison of Metabolite Measurements for Metabolomics Data Integration

Izumi, Yoshihiro; Mizutani, Fumio; Hirayama, Akiyoshi; Ikeda, Kazutaka; Kita, Yoshiaki; Horie, Kazuyuki; Saigusa, Daisuke; Saito, Kosuke; Sawada, Yuji; Nakanishi, Hiroki; Okahashi, Nobuyuki; Takahashi, Masatomo; Nakao, Motonao; Hata, Kunihiko; Hoshi, Yosuke; Morihara, Motohiko; Tanabe, Kenichi; Bamba, Takeshi; Oda, Yoshiya

doi:10.3390/metabo9110257

Cited by 38 publications

(53 citation statements)

References 44 publications

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“…× 50 mm, 4 μm particle size, Thermo Fisher Scientific) and a Dionex IonPac AS11-HC-4 μm column (2 mm i.d. × 250 mm, 4 μm particle size, Thermo Fisher Scientific) coupled with a Q Exactive, high-performance benchtop quadrupole Orbitrap high-resolution tandem mass spectrometer (Thermo Fisher Scientific) (IC/HRMS/MS) [ 29 ]. Cationic polar metabolites (e.g., amino acids, bases, and nucleosides) were analyzed via liquid chromatography (Nexera X2 UHPLC system, Shimadzu Co., Kyoto, Japan) with a Discovery HS F5 column (2.1 mm i.d.…”

Section: Skeletal Muscle Performancementioning

confidence: 99%

Skeletal muscle-specific Keap1 disruption modulates fatty acid utilization and enhances exercise capacity in female mice

et al. 2021

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Skeletal muscle health is important for the prevention of various age-related diseases. The loss of skeletal muscle mass, which is known as sarcopenia, underlies physical disability, poor quality of life and chronic diseases in elderly people. The transcription factor NRF2 plays important roles in the regulation of the cellular defense against oxidative stress, as well as the metabolism and mitochondrial activity. To determine the contribution of skeletal muscle NRF2 to exercise capacity, we conducted skeletal muscle-specific inhibition of KEAP1, which is a negative regulator of NRF2, and examined the cell-autonomous and non-cell-autonomous effects of NRF2 pathway activation in skeletal muscles. We found that NRF2 activation in skeletal muscles increased slow oxidative muscle fiber type and improved exercise endurance capacity in female mice. We also observed that female mice with NRF2 pathway activation in their skeletal muscles exhibited enhanced exercise-induced mobilization and β-oxidation of fatty acids. These results indicate that NRF2 activation in skeletal muscles promotes communication with adipose tissues via humoral and/or neuronal signaling and facilitates the utilization of fatty acids as an energy source, resulting in increased mitochondrial activity and efficient energy production during exercise, which leads to improved exercise endurance.

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Section: Skeletal Muscle Performancementioning

confidence: 99%

Skeletal muscle-specific Keap1 disruption modulates fatty acid utilization and enhances exercise capacity in female mice

et al. 2021

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“…compared the fold-change between two cell lines across 12 different laboratories. Their results suggested that relative values obtained from different analytical setups can be combined when the same sample was analyzed (Izumi et al 2019 ). Similarly, Triebl et al found that the use of shared reference materials beyond in-house quality controls (QCs) can even further improve the quality of data from shared studies and measurements (Triebl et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Comparison of lipidome profiles of Caenorhabditis elegans—results from an inter-laboratory ring trial

et al. 2021

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Introduction Lipidomic profiling allows 100s if not 1000s of lipids in a sample to be detected and quantified. Modern lipidomics techniques are ultra-sensitive assays that enable the discovery of novel biomarkers in a variety of fields and provide new insight in mechanistic investigations. Despite much progress in lipidomics, there remains, as for all high throughput “omics” strategies, the need to develop strategies to standardize and integrate quality control into studies in order to enhance robustness, reproducibility, and usability of studies within specific fields and beyond. Objectives We aimed to understand how much results from lipid profiling in the model organism Caenorhabditis elegans are influenced by different culture conditions in different laboratories. Methods In this work we have undertaken an inter-laboratory study, comparing the lipid profiles of N2 wild type C. elegans and daf-2(e1370) mutants lacking a functional insulin receptor. Sample were collected from worms grown in four separate laboratories under standardized growth conditions. We used an UPLC-UHR-ToF–MS system allowing chromatographic separation before MS analysis. Results We found common qualitative changes in several marker lipids in samples from the individual laboratories. On the other hand, even in this controlled experimental system, the exact fold-changes for each marker varied between laboratories. Conclusion Our results thus reveal a serious limitation to the reproducibility of current lipid profiling experiments and reveal challenges to the integration of such data from different laboratories.

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“…The CE-TOFMS that was used in the TMCS has the advantage of identifying ionic metabolites, which are major metabolites in cells. However, the reliability of metabolome data from CE–MS has been of great concern, and recently the data have been investigated from various aspects including migration timing (electrophoretic mobility) [ 32 ], and quantification of metabolites at the inter-laboratory [ 37 ] and cohort [ 2 ] levels. In this study, we described an approach to evaluate the reliability of automatically extracted peaks using the cohort study and proposed a pipeline to filter reliable peaks efficiently.…”

Section: Discussionmentioning

confidence: 99%

Quality Assessment of Untargeted Analytical Data in a Large-Scale Metabolomic Study

Saito

Sugimoto

Hirayama

et al. 2021

JCM

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Large-scale metabolomic studies have become common, and the reliability of the peak data produced by the various instruments is an important issue. However, less attention has been paid to the large number of uncharacterized peaks in untargeted metabolomics data. In this study, we tested various criteria to assess the reliability of 276 and 202 uncharacterized peaks that were detected in a gathered set of 30 plasma and urine quality control samples, respectively, using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). The linear relationship between the amounts of pooled samples and the corresponding peak areas was one of the criteria used to select reliable peaks. We used samples from approximately 3000 participants in the Tsuruoka Metabolome Cohort Study to investigate patterns of the areas of these uncharacterized peaks among the samples and clustered the peaks by combining the patterns and differences in the migration times. Our assessment pipeline removed substantial numbers of unreliable or redundant peaks and detected 35 and 74 reliable uncharacterized peaks in plasma and urine, respectively, some of which may correspond to metabolites involved in important physiological processes such as disease progression. We propose that our assessment pipeline can be used to help establish large-scale untargeted clinical metabolomic studies.

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Inter-Laboratory Comparison of Metabolite Measurements for Metabolomics Data Integration

Cited by 38 publications

References 44 publications

Skeletal muscle-specific Keap1 disruption modulates fatty acid utilization and enhances exercise capacity in female mice

Skeletal muscle-specific Keap1 disruption modulates fatty acid utilization and enhances exercise capacity in female mice

Comparison of lipidome profiles of Caenorhabditis elegans—results from an inter-laboratory ring trial

Quality Assessment of Untargeted Analytical Data in a Large-Scale Metabolomic Study

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