Pattern recognition and biomarker validation using quantitative<sup>1</sup>H-NMR-based metabolomics

Serkova, Natalie J.; Niemann, Claus U.

doi:10.1586/14737159.6.5.717

Cited by 149 publications

(125 citation statements)

References 101 publications

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“…MS determines the composition of particles based on the mass-to-charge ratio in charged particles. Each technique has distinct advantages and disadvantages (13,27). The major advantages of 1 H-NMR include its unbiased metabolite detection, quantitative nature, and reproducibility (6,7,26).…”

Section: Analytical Platforms For Metabolite Detection and Quantificamentioning

confidence: 99%

“…This is a scientific challenge of the systems biology approach and highlights the need for new knowledge of the relationships and interactions between the components of the system (Figure 2). Monitoring fluctuations of certain metabolites (endogenous low-molecular weight molecules) in body fluids, such as blood (including plasma and serum) and urine, is an important way to detect various human pathologies, including cancer, cardiovascular disease, diabetes, and drug toxicity (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). These data are also needed to construct powerful top-down systems biology tools that link the "omics" disciplines (16).…”

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confidence: 99%

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The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

Serkova

Standiford²,

Stringer

2011

Am J Respir Crit Care Med

167

124

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Metabolomics, a science of systems biology, is the global assessment of endogenous metabolites within a biologic system and represents a "snapshot" reading of gene function, enzyme activity, and the physiological landscape. Metabolite detection, either individual or grouped as a metabolomic profile, is usually performed in cells, tissues, or biofluids by either nuclear magnetic resonance spectroscopy or mass spectrometry followed by sophisticated multivariate data analysis. Because loss of metabolic homeostasis is common in critical illness, the metabolome could have many applications, including biomarker and drug target identification. Metabolomics could also significantly advance our understanding of the complex pathophysiology of acute illnesses, such as sepsis and acute lung injury/acute respiratory distress syndrome. Despite this potential, the clinical community is largely unfamiliar with the field of metabolomics, including the methodologies involved, technical challenges, and, most importantly, clinical uses. Although there is evidence of successful preclinical applications, the clinical usefulness and application of metabolomics in critical illness is just beginning to emerge, the advancement of which hinges on linking metabolite data to known and validated clinically relevant indices. In addition, other important aspects, such as patient selection, sample collection, and processing, as well as the needed multivariate data analysis, have to be taken into consideration before this innovative approach to biomarker discovery can become a reliable tool in the intensive care unit. The purpose of this review is to begin to familiarize clinicians with the field of metabolomics and its application for biomarker discovery in critical illnesses such as sepsis.

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Section: Analytical Platforms For Metabolite Detection and Quantificamentioning

confidence: 99%

mentioning

confidence: 99%

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

Serkova

Standiford²,

Stringer

2011

Am J Respir Crit Care Med

167

124

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“…In these applications, statistical pattern recognition techniques were used for data reduction and analysis (23,26,29,41,43), thereby allowing extraction of metabolic information from the complexity of the information-rich data (4,9,14). Although much of this research addressed metabolic variations induced by toxicological exposures (18,24,32), early studies with human plasma demonstrated that 1 H-NMR spectroscopy can also be used to discriminate individuals with cardiovascular disease (4,8,40).…”

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confidence: 99%

Individual variation in macronutrient regulation measured by proton magnetic resonance spectroscopy of human plasma

Park¹,

Kim²,

Wang³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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DP. Individual variation in macronutrient regulation measured by proton magnetic resonance spectroscopy of human plasma. Am J Physiol Regul Integr Comp Physiol 297: R202-R209, 2009. First published May 20, 2009 doi:10.1152/ajpregu.90757.2008.-Proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy of plasma provides a global metabolic profiling method that shows promise for clinical diagnostics. However, cross-sectional studies are complicated by a lack of understanding of intraindividual variation, and this limits experimental design and interpretation of data. The present study determined the diurnal variation detected by 1 H NMR spectroscopy of human plasma. Data reduction methods revealed three time-of-day metabolic patterns, which were associated with morning, afternoon, and night. Major discriminatory regions for these time-of-day patterns included the various kinds of lipid signals , and the region between 3 and 4 ppm heavily overlapped with amino acids that had ␣-CH and ␣-CH2. The phasing and duration of time-of-day patterns were variable among individuals, apparently because of individual difference in food processing/digestion and absorption and clearance of macronutrient energy sources (fat, protein, carbohydrate). The times of day that were most consistent among individuals, and therefore most useful for cross-sectional studies, were fasting morning (0830 -0930), postprandial afternoon (1430 -1630), and nighttime samples (0430 -0530). Importantly, the integrated picture of metabolism provided by 1 H-NMR spectroscopy of plasma suggests that this approach is suitable to study complex regulatory processes, including eating patterns/eating disorders, upper gastrointestinal functions (gastric emptying, pancreatic, biliary functions), and absorption/clearance of macronutrients. Hence, 1 H-NMR spectroscopy of plasma could provide a global metabolic tolerance test to assess complex processes involved in disease, including eating disorders and the range of physiological processes causing dysregulation of energy homeostasis. metabolomics; diurnal variation; eating disorders; gastrointestinal regulation GLOBAL METABOLIC PROFILING coupled with bioinformatic methods offers an approach to study the integration of macronutrient energy metabolism and can be useful to detect disease, toxicity, and nutritional deficiency (11,23,30,36). A variety of metabolic profiling methods are available, including gas chromatography-mass spectrometry, liquid chromatographymass spectrometry, and NMR spectroscopy (10,31,39). In view of its capability to handle multiple specimens in a high-throughput, semiautomated system, 1 H-NMR may offer unique insight into the in vivo metabolism of macronutrients (1, 2, 9). Dysfunction in macronutrient metabolism, i.e., carbohydrate, fat, protein, and alcohol, is relevant to obesity, metabolic syndrome, diabetes, cardiovascular disease and other common pathological conditions (19,25).Pioneering studies by Nicholson and coworkers (3, 24, 27, 35) established the utility of 1 H NMR spectroscopy f...

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“…This can be done through collection of global metabolic data with modern spectroscopic techniques and appropriate statistical approaches (29,36). Nuclear magnetic resonance (NMR) spectroscopy is one of the major techniques for metabolomics analysis because it allows for simultaneous assessment and quantification of small-molecule metabolites in the concentration range above 10 M. Thus quantitative assessment of various metabolite classes (such as sugars, amino acids, osmolytes, lipids, high-energy phosphates) in tissues and biological fluids can be performed with high-resolution 1 H-and 31 P-NMR spectroscopy.…”

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confidence: 99%

Quantitative analysis of liver metabolites in three stages of the circannual hibernation cycle in 13-lined ground squirrels by NMR

Serkova

Rose

Epperson

et al. 2007

Physiological Genomics

105

106

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lined ground squirrels and other circannual hibernators undergo profound physiological changes on an annual basis, transitioning from summer homeothermy [body temperature (Tb) ϳ37°C] to winter heterothermy (Tb cycling between 0°C and 37°C). We hypothesize that these physiological changes are reflected in biochemical changes that provide mechanistic insights into, and biomarkers for, hibernation states. Here we report the results of an NMR-based metabolomics analysis of liver extracts from ground squirrels in three distinct physiological states of circannual hibernation: summer active (SA), late torpor (LT), and reentering torpor (Ent) after one of the euthermic arousals. Of the 43 identified and quantified metabolites, 36 differed among these three states and fell into two patterns of variation: 1) SA differed from both of the two winter states; or 2) the two winter states differed from each other, but one of the two was not different from SA. Concentrations of hepatic glucose, lactate, alanine, succinate, ␤-hydroxybutyrate, glutamine, and betaine were identified as robust hepatic biomarkers that together distinguish among animals in these three states of the circannual hibernation rhythm. These data are consistent with a proposed two-switch model of hibernation, in which setting the summer-winter switch to winter enables expression of a distinct torpor-arousal switch. The summer-winter switch is characterized by the metabolites associated with the well-known switch from carbohydrate to lipid fuel utilization during hibernation. The torpor-arousal switch is characterized by the accumulation of metabolites of nitrogen (glutamine) and phospholipid (betaine) catabolism in LT with the capacity to act as protective osmolytes. metabolomics; nitrogen metabolism; osmolytes; Spermophilus tridecemlineatus; torpor MAMMALIAN HIBERNATORS are uniquely able to orchestrate and survive extended periods of extremely low body temperature (T b ) and metabolic, respiratory, and heart rates in a state called torpor. The deep, multiday periods of torpor that characterize hibernation alternate with periodic short arousals that reverse the dramatic physiological depressions associated with the torpid state (reviewed in Ref. 5). Thus hibernators, including 13-lined ground squirrels (Spermophilus tridecemlineatus), are homeothermic like most mammals in summer but switch to heterothermy in winter (Fig. 1). The biochemical consequences of periodic arousals from torpor are complex and come with tremendous costs. Although hibernation is a strategy that saves large amounts of energy over the winter compared with remaining euthermic (ϳ90%), most of the energy used in winter (Ͼ70%) is used to fuel these interbout arousals (Ref. 22 and references therein). Hence the arousals are an enigma-Why arouse when remaining torpid would save so much more energy? It has been suggested that hibernators must rewarm to restore or remove a metabolic imbalance (Ref. 27, chapter 6).Metabolomics seeks to identify and quantify the low-molecular-weight endogenous co...

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Pattern recognition and biomarker validation using quantitative¹H-NMR-based metabolomics

Cited by 149 publications

References 101 publications

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

Individual variation in macronutrient regulation measured by proton magnetic resonance spectroscopy of human plasma

Quantitative analysis of liver metabolites in three stages of the circannual hibernation cycle in 13-lined ground squirrels by NMR

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Pattern recognition and biomarker validation using quantitative1H-NMR-based metabolomics

Cited by 149 publications

References 101 publications

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

Individual variation in macronutrient regulation measured by proton magnetic resonance spectroscopy of human plasma

Quantitative analysis of liver metabolites in three stages of the circannual hibernation cycle in 13-lined ground squirrels by NMR

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Pattern recognition and biomarker validation using quantitative¹H-NMR-based metabolomics