Systematic Review of NMR-Based Metabolomics Practices in Human Disease Research

Huang, Katherine; Thomas, Natalie; Gooley, Paul R.; Armstrong, Christopher W.

doi:10.3390/metabo12100963

Cited by 3 publications

(1 citation statement)

References 242 publications

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“…In addition to the possible retrieving of the proper endocrine pattern through weight lowering, other additional or parallel mechanisms on the testis function associated with nutritional-based ketosis, including fertility outcomes, are largely underinvestigated [ 6 , 15 ]. The biofluid profile of low/mid molecular weight metabolites has recently become a promising research field for the pathophysiological biomarkers of organ function [ 16 ]. This is particularly the case of human semen in which the analysis of metabolite composition showed interesting correlations with fertility outcomes that are currently uncovered by classical morphology-based semen analysis [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Ketone Body β-Hydroxy-Butyrate Sustains Progressive Motility in Capacitated Human Spermatozoa: A Possible Role in Natural Fertility

et al. 2023

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Background Calorie restriction is recognized as a useful nutritional approach to improve the endocrine derangements and low fertility profile associated with increased body weight. This is particularly the case for dietary regimens involving ketosis, resulting in increased serum levels of ketone bodies such as β-hydroxy-butyrate (β-HB). In addition to serum, β-HB is detected in several biofluids and β-HB levels in the follicular fluid are strictly correlated with the reproductive outcome in infertile females. However, a possible direct role of ketone bodies on sperm function has not been addressed so far. Methods Semen samples were obtained from 10 normozoospermic healthy donors attending the University Andrology Unit as participants in an infertility survey programme. The effect of β-HB on cell motility in vitro was evaluated on isolated spermatozoa according to their migratory activity in a swim-up selection procedure. The effect of β-HB on spermatozoa undergone to capacitation was also assessed. Results Two hours of exposure to β-HB, 1 mM or 4 mM, proved to be ineffective in modifying the motility of freshly ejaculated spermatozoa isolated according to the migratory activity in a swim-up procedure (all p values > 0.05). Differently, sperm maintenance in 4 mM β-HB after capacitation was associated with a significantly higher percentage of sperm cells with progressive motility compared to β-HB-lacking control (respectively, 67.6 ± 3.5% vs. 55.3 ± 6.5%, p = 0.0158). Succinyl-CoA transferase inhibitor abolished the effect on motility exerted by β-HB, underpinning a major role for this enzyme. Conclusion Our results suggest a possible physiological role for β-HB that could represent an energy metabolite in support of cell motility on capacitated spermatozoa right before encountering the oocyte.

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Section: Introductionmentioning

confidence: 99%

Ketone Body β-Hydroxy-Butyrate Sustains Progressive Motility in Capacitated Human Spermatozoa: A Possible Role in Natural Fertility

et al. 2023

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Matrix Linear Models for connecting metabolite composition to individual characteristics

Farage,

Zhao,

Choi

et al. 2023

Preprint

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High-throughput metabolomics data provide a detailed molecular window into biological processes. We consider the problem of assessing how the association of metabolite levels with individual (sample) characteristics such as sex or treatment may depend on metabolite characteristics such as pathway. Typically this is one in a two-step process: In the first step we assess the association of each metabolite with individual characteristics. In the second step an enrichment analysis is performed by metabolite characteristics among significant associations. We combine the two steps using a bilinear model based on the matrix linear model (MLM) framework we have previously developed for high-throughput genetic screens. Our framework can estimate relationships in metabolites sharing known characteristics, whether categorical (such as type of lipid or pathway) or numerical (such as number of double bonds in triglycerides). We demonstrate how MLM offers flexibility and interpretability by applying our method to three metabolomic studies. We show that our approach can separate the contribution of the overlapping triglycerides characteristics, such as the number of double bonds and the number of carbon atoms. The proposed method have been implemented in the open-source Julia package,MatrixLM. Data analysis scripts with example data analyses are also available.

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A Deep Learning Approach to Analyze NMR Spectra of SH-SY5Y Cells for Alzheimer’s Disease Diagnosis

et al. 2023

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The SH-SY5Y neuroblastoma cell line is often used as an in vitro model of neuronal function and is widely applied to study the molecular events leading to Alzheimer’s disease (AD). Indeed, recently, basic research on SH-SY5Y cells has provided interesting insights for the discovery of new drugs and biomarkers for improved AD treatment and diagnosis. At the same time, untargeted NMR metabolomics is widely applied to metabolic profile analysis and screening for differential metabolites, to discover new biomarkers. In this paper, a compression technique based on convolutional autoencoders is proposed, which can perform a high dimensionality reduction in the spectral signal (up to more than 300 times), maintaining informative features (guaranteed by a reconstruction error always smaller than 5%). Moreover, before compression, an ad hoc preprocessing method was devised to remedy the scarcity of available data. The compressed spectral data were then used to train some SVM classifiers to distinguish diseased from healthy cells, achieving an accuracy close to 78%, a significantly better performance with respect to using standard PCA-compressed data.

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Systematic Review of NMR-Based Metabolomics Practices in Human Disease Research

Cited by 3 publications

References 242 publications

Ketone Body β-Hydroxy-Butyrate Sustains Progressive Motility in Capacitated Human Spermatozoa: A Possible Role in Natural Fertility

Ketone Body β-Hydroxy-Butyrate Sustains Progressive Motility in Capacitated Human Spermatozoa: A Possible Role in Natural Fertility

Matrix Linear Models for connecting metabolite composition to individual characteristics

A Deep Learning Approach to Analyze NMR Spectra of SH-SY5Y Cells for Alzheimer’s Disease Diagnosis

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