= Discovery stage.
= Translation stage.
= Clinically available.
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= Discovery stage.
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= Translation stage.
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= Clinically available.
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Podium Presentations for Metabolites & Metabolomics |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Wednesday at 9:00
INTRODUCTION: Metabolite profiling – or metabolomics – presents a powerful global approach to measure shifts in metabolites as functional readouts of cellular state. Metabolites can complement upstream biochemical information obtained from genes, transcripts, and proteins and advance our understanding of how cells are altered in health and disease. Unfortunately, the great success in the characterization of genes, transcripts and proteins has currently no parallel in metabolites. Metabolomic studies are revealing large numbers of naturally occurring metabolites that cannot be characterized because their chemical structures and spectrometric data are not available. This is preventing metabolomics from evolving as fast as other omic sciences, and thus it is restricting the integration of multiple layers of omic data to gain more insights into the emergence of observed phenotypes. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Wednesday at 11:20
Introduction |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Wednesday at 11:40
INTRODUCTION: Burn injury can be a devastating trauma, affecting millions of people worldwide, with long-term personal and social implications for patients. Burns can result in life-limiting chronic pain, often refractory to treatment. Mechanisms behind burn injury are poorly understood and there has been little research into the molecular basis of burns and subsequent pain. It is important to explore the local signalling environment, but studies are often destructive in nature and preclude the collection of longitudinal temporal data. Microdialysis is a sampling method allowing the in vivo collection of solutes primarily from the extracellular interstitium and is ideal for the study of burn injury. Metabolomics offers an unbiased approach to the elucidation of metabolites involved in pathological events. Coupled with mass spectrometry, it provides a sensitive platform for the detection of metabolic changes due to burn injury. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Wednesday at 14:30
INTRODUCTION: |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Wednesday at 14:50
Introduction. Podocyturia is a possible early sign of kidney abnormalities in patients. Currently, kidney damages are assessed using proteinuria measurements and the estimated glomerular filtration rate. Unfortunately, these parameters might not always be efficient in early detection of all patients. Most analytical techniques for the analysis of podocyturia are tedious, time-consuming, and may lead to results variability. We opted to develop a reliable methodology for podocyturia evaluation in patients with kidney involvement. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Wednesday at 15:10
INTRODUCTION: A key metabolic alteration in tumour cells is increased dependency on glycolysis, resulting in the production of lactate which is transported out of cells by monocarboxylate transporters (MCT1 & MCT4) which are therefore a therapeutic target in cancer. Current literature suggests that inhibition of MCT1 in preclinical models can constrain cancer cell growth in tumours with low MCT4 expression. To date the systemic pharmacodynamic effects of the small-molecule non-competitive inhibitor of MCT1, AZD3965, the agent of study in this first-in-class (FIC) trial CRUKD12/004, have not been fully characterised. Preclinical metabolomics studies conducted at Imperial College London indicated that AZD3965 exposure caused increases in lactate, ketone bodies (also MCT1 substrates) and citrate in blood plasma and urine independently of tumour burden and tumour expression of MCT1, and also caused decreases in fatty acids in blood plasma. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 08:30
Background / Objectives: Cervical cancer is the 4th most common cancer among women while its incidence is expected to rise by 43% in the UK by 2035 (Cancer Research UK, 2019). The microscopic examination of cervical cells currently carried out to screen asymptomatic women is prone to human error and can lead to high numbers of false-positives and false-negatives. Primary HPV DNA testing has been shown to be more accurate in screening and therefore is projected to replace cytology in the UK by the end of 2019 (Rebolj et al., 2019). Rapid evaporative ionization mass spectrometry (REIMS) is an innovative technique that allows interrogation of biological samples without any need for laborious sample preparation. Our main objective is to establish whether REIMS can be employed for the detection and grading of pre-invasive cervical changes. We also seek to assess the ability of REIMS to distinguish women with high-risk HPV (hrHPV) infection from women without infection. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 8:50
INTRODUCTION: The human gut microbiota represents a pivotal environmental influence on the metabolism and overall health of the host. The immunomodulatory function of microbiota is mediated via the interaction of microbial metabolites with xenobiotic receptors expressed in immune cells and tissues. For instance, microbial catabolites of aromatic amino acids (i.e. tryptophan and tyrosine) were reported to activate pregnane X receptor (PXR) or aryl hydrocarbon receptor (AHR) in a ligand-specific fashion. The immune-metabolic homeostasis may be explored using quantitative metabolic profiling and targeted protein assays. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 9:10
Introduction: |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 10:30
Background: Endothelial dysfunction (ED) contributes to diseases of the vasculature by influencing blood pressure, clotting and transport of fluids, nutrients and immune cells. Metabolic phenotypes associated with ED are not well characterized due to difficulties in assessing endothelial metabolism in situ. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 11:10
Introduction: The adrenal cortex and gonads produce steroid hormones involved in salt and glucose homeostasis, blood pressure regulation, stress response and sex differentiation. These hormones are produced via a series of enzymatic steps and metabolites of steroids from each step are excreted and measurable in urine. Inborn disorders of steroidogenesis result from genetic mutations in distinct enzymes, causing a block in hormone production and lead to several forms of Congenital Adrenal Hyperplasia (CAH) and differences in sex development (DSD). Each enzyme deficiency is characterised by a distinct pattern of altered excretion of individual steroid metabolites relating to the specific enzymatic block. Ratios of urine steroid metabolites measured by gas chromatography-mass spectrometry (GC-MS) can be employed as surrogates of distinct steroidogenic enzyme activities. Widespread use of GC-MS multi-steroid profiling for rapid diagnosis of these disorders in the acute setting is often hampered by lack of specialist expertise. Here, we developed a novel steroid metabolomics approach for the detection and differentiation of inborn steroidogenic disorders, comparing its performance to that of conventional biochemical analysis by established steroid metabolite ratios. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 13:15
Introduction: Risk assessment of new or existing chemicals finds a bottleneck in the evaluation of their potential as toxicants. Current approaches are too resource intensive in terms of time, money and animal use, thus limiting the number of substances which can be assayed. Chemical risk assessment using in vitro biological models such as human cell cultures allows to increase throughput while reducing cost and animal use. In such models, untargeted metabolomics can unveil triggered adverse outcome pathways (AOP) without the need for previous hypotheses. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 13:35
Introduction |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 13:55
Non-Functionalized silica nanoparticles (SiNPs) are some of the widely used nanomaterial in diverse industrial sectors and nanoparticle based drug delivery applications. In industrial manufacturing environment SiNPs can possibly comes in contact with employees. Studies of cellular level toxicity effects of SiNPs in human cell lines are pivotal in the metabolite based biomarker discovery. Human lung epithelial cells (A549) are used to decipher the overall cellular level metabolic changes, non-targeted metabolite profiling with HILIC (hydrophilic interaction liquid chromatography) UPLC-HRMS method in a data dependent (DDA) mode was developed for this study. From the identified metabolome data and corresponding dysregulation in the metabolome of A549 biochemical pathways, our preliminary finding indicated 8 nm SiNPs elicit observable effects on the A549 cellular metabolism over larger SiNPs.The study identified some insights in early stage selective metabolite markers for nanomaterial related cytotoxicity in human cell line.Identified metabolites were annotated to pathways related to glutathione mediated detoxification, amino acid degradation, central carbohydrate metabolism and nucleotide metabolism with statistical significance (p < 0.01). |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 6 (Doppler Hall) on Thursday at 13:55
Introduction: There is a pressing need to develop new non-invasive screening tests for Oesophago-gastric (OG) cancer due to its high prevalence and poor survival. Previous studies have reported that urinary volatile organic compounds (VOCs) reflect human pathophysiological status. GC-MS based methods are the main approaches for urinary VOC profiling. However, biomarker discovery is limited by often inefficient and labour-intensive solvent extractions, by chromatographic resolution and by the unavailability of a complete, detailed, and high-throughput data-preprocessing methodology for large-scale untargeted VOC analysis of urine samples. Novel HiSorb sorptive extraction and conventional solid phase microextraction (SPME) are both tested and evaluated. GCxGC combined with TOF-MS is employed and offers outstanding identification capabilities. By coupling HiSorb/SPME with GCxGC-TOF-MS, this project aims to discover new predictive biomarkers for OG cancer. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 14:30
Introduction: There is a need to develop new diagnostic tools to diagnose and subtype patients with dysregulated steroidogenesis. Methods used today may require medication to be altered, multistep testing, imaging and even surgery to be able to make a final diagnosis. We hypothesize that it is possible to avoid many of these steps if the correct biomarkers or plasma steroid profiles are identified for patients suffering from these steroid dysregulation diseases, allowing diagnosis using only a single plasma sample. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 14:50
INTRODUCTION: |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 15:10
Introduction: Cancer is the second leading cause of death globally and is estimated to account for 9.6 million death in 2018 (WHO). Breast cancer (BC) remain the most common cancer in women and is ranked as the fifth amongst all cancers followed by colorectal, lung, cervix, and stomach cancers. The late diagnosis, using invasive and expensive procedures and the critical lack of medical and laboratorial infrastructures in the developing countries, are certainly two key contributing factors for this scenario. Therefore, more sensitive and specific diagnostic methods are urgently required. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 15:45
Introduction: Lactic acid is an organic acid found in two enantiomeric forms: the L- and D-lactate stereoisomers. D-lactic acid is produced from bacteria inhabiting the gut and also from mammalian methylglyoxal metabolism. In humans, the majority of systemic D-lactate is derived from the bacterial metabolism of carbohydrate in the upper GI tract. In pathological states, intestinal permeability is increased elevating the uptake of bacterial D-lactate from the gut. Circulating D-lactate concentrations may therefore provide a useful diagnostic tool for bacterial infections, gut permeability and GI health and disease. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 16:05
Faecal metabolomics allows for the non-invasive study of biomarkers in gastrointestinal (GI) disease. Current analytical techniques are limited in their applicability as they can lack in sensitivity (Nuclear Magnetic Resonance Spectroscopy) or require time-intensive sample preparation (Gas Chromatography - Mass Spectrometry). Here, we present the optimisation of LA-REIMS for faecal sample analysis and its implementation into a novel high-throughput application of LA-REI-MSI for the near-real time analysis and mapping of metabolites in whole fresh or frozen human faecal samples. |
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Topic(s): Metabolites & Metabolomics
To be presented in Track 1 (Mozart 1-3) on Thursday at 16:25
INTRODUCTION: Steroids play a crucial role in homeostasis of many biological processes including spermatogenesis, thus being responsible for some male infertility issues. Although steroids have been largely studied in many biological matrices (such as urine and plasma), there is very limited information of the steroid content in seminal liquid and its potential study as potential indicators of male infertility and other conditions. |
Poster Presentations for Metabolites & Metabolomics |
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Topic(s): Metabolites & Metabolomics
Poster #1d View Map
INTRODUCTION: Genome wide association studies have identified the FTO gene as the first susceptibility gene of obesity. Previous studies have suggested a role of FTO in nucleic acid repair or modification, but how this leads to an alteration in energy homeostasis is unclear. In the present study, we utilized targeted metabolomics in an attempt to further elucidate mechanisms underlying the action of the FTO gene. |
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Topic(s): Metabolites & Metabolomics
Poster #2a View Map
INTRODUCTION: The untargeted nature of metabolomics allows measurement of biofluid chemistry related to both endogenous metabolism and host-environment exposures (i.e. the exposome). Comprehensive coverage of chemically diverse metabolites present in human blood products benefits from the use of multiple methods, each oriented toward a small molecule subset generally segregated by polarity and hydrophobicity. Whilst recent developments in LC-MS profiling methodologies have delivered numerous solutions for the analysis of polar molecules (e.g. via HILIC-MS) and complex lipids, the analysis of moderately hydrophobic and amphipathic molecules in blood products (including much of the exposome) by RPC methodology, is complicated by the suppressive effects of lipids on the ionisation of low molecular weight (LMW) metabolites. Efficient and inexpensive solutions are required for the separation of small molecules from the remaining sample matrix fit for large scale and high throughput applications. |
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Topic(s): Metabolites & Metabolomics
Poster #2c View Map
Introduction: Zearalenone or F-2 mycotoxin is a heat-stable, potent estrogenic metabolic product of some Fusarium and Gibberella species, found in cereal crops like maize, oats, wheat, rice and barley. Due to its similarity to naturally-occurring estrogens (17β-estradiol), zearalenone and its main metabolites (α-zearalenol, β-zearalenol, zeranol and taleranol) are considered by World Health Organization and European Commission as endocrine-disrupting chemicals and a possible cause of carcinogenesis. |
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Topic(s): Metabolites & Metabolomics
Poster #5b View Map
Introduction: Zika virus (ZIKV) is a flavivirus transmitted by Aedes aegypti mosquito, with high incidence of cases on Americas between 2015 and 2016. Although 80% of the cases are asymptomatic, ZIKV infection was associated to neurological complications such as Guillain-Barré syndrome and microcephaly. Based on these reports several initiatives started to understand viral infection process in human and mosquito cells. During experimental investigations it was demonstrated that ZIKV can impair neuronal growth, reduce neural stem cell and even mediate cell death. A hypothesis about the oncolytic potential of ZIKV due its ability of cell growth impairment was raised and later confirmed by in vitro and in vivo studies with glioblastoma cells. The antiproliferative effect of a ZIKV prototype (ZVp) was tested for several types of tumor cell resulting in ZVp activity against prostate cancer cells (PC-3). However, little is known about the cellular mechanisms associated prostate cancer cell death induced by Zika moieties. |
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Topic(s): Metabolites & Metabolomics
Poster #6b View Map
<b>Introduction</b> |
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Topic(s): Metabolites & Metabolomics
Poster #9a View Map
Introduction: Vitamin B12 deficiency can lead to potentially irreversible neurological symptoms such as memory deficits and gait ataxia. Up to 40% of older adults show metabolic abnormalities due to vitamin B12 deficiency. However, most adults have normal levels of serum B12 so that this condition often remains under-recognized. Metabolic B12 deficiency causes an elevation of serum methylmalonic acid (MMA), an expensive test rarely available in clinical settings. Urine MMA also increases in cases of B12 deficiency, but it is unclear whether it correlates with serum MMA and thus be reliable for diagnostic purposes. Also, various inborn errors of metabolism lead to increased MMA levels in urine and plasma. |
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Topic(s): Metabolites & Metabolomics
Poster #9d View Map
Aim: To identify the serum metabolomics signature that is correlated with the chemoradiosensitivity of esophageal squamous cell carcinoma (ESCC). |
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Topic(s): Metabolites & Metabolomics
Poster #10c View Map
Introduction: Metabolic disorders are caused by the accumulation of metabolites in the body which lead to irreversible physiological effects. The first-tier screening procedure for these disorders is typically performed on dried blood spot (DBS) samples by the MS/MS system. When a newborn screen is found to be positive, second-tier tests using plasma samples are provided to reduce false-positive and false-negative results. To prevent resampling and provide comfort for newborns, it is more convenient to use the same DBS sample taken in the first stage of screening. Objective: The objective of this study was development of a method based on the DBS instead of plasma analyses for each aminoacidemia disorder that could potentially use as second-tier tests. Methods: To optimize the extraction conditions of 19 naturally occurring amino acids from DBS, the central composite design and response surface methodology were used to demonstrate the influence of effective factors on the responses. Also, four different types of validation were compared, and the best validation method was selected. |
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Topic(s): Metabolites & Metabolomics
Poster #11b View Map
Background: Obesity amongst women of reproductive age is increasingly common in developed nations and has been shown to adversely affect childhood cardio-metabolic, respiratory and cognitive-related health outcomes in offspring. Metabolomic signatures of obesity are readily captured in biofluids samples and could potentially provide a molecular barometer for monitoring excessive gestational weight gain (GWG) and postpartum weight loss (WL) in overweight/obese pregnant women. |
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Topic(s): Metabolites & Metabolomics
Poster #13d View Map
INTRODUCTION: Most clinical laboratories measure total 25-hydroxy vitamin D by immunoassays with variable analytical performance. Other relevant metabolites, such as 25-hydroxy vitamin D2 (25(OH)D2), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and 25,26-dihydroxyvitamin D3 (25,26(OH)2D3) may provide additional information beyond the simple measurement of 25(OH)D. Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) allows the simultaneous measurement of multiple vitamin D metabolites with high sensitivity and specificity. |
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Topic(s): Metabolites & Metabolomics
Poster #15b View Map
Introduction |
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Topic(s): Metabolites & Metabolomics
Poster #17a View Map
Introduction: |
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Topic(s): Metabolites & Metabolomics
Poster #17c View Map
INTRODUCTION: Vitamin D plays a key role in metabolic processes in human body. Despite the growing social awareness, its large deficit is still being observed, which is particularly important in the case of pregnant women. Vitamin D concentration in the fetal period strictly depends on the maternal concentration. Deficiency of this vitamin in the newborn affects a number of diseases, including abnormal development of the bone or immune system. For this reason, preventing deficiency from the first days of life is extremely important. |
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Topic(s): Metabolites & Metabolomics
Poster #18c View Map
INTRODUCTION: Glutaric aciduria type 1 (GA-1; OMIM#231670) is an autosomal recessive inborn error of metabolism caused by deficiency of glutaryl-CoA dehydrogenase (GCDH) located in the catabolic pathways of L-lysine, L-hydroxylysine, and L-tryptophan. The enzymatic defect gives rise to neurotoxic metabolite glutaric acid (GA) and 3- hydroxyglutaric acid |
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Topic(s): Metabolites & Metabolomics
Poster #19e View Map
Introduction |
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Topic(s): Metabolites & Metabolomics
Poster #20a View Map
INTRODUCTION: Acylcarnitine profiling is routinely performed in order to quantitatively screen for disorders related to β-oxidation and / or organic acid metabolism. Today many laboratories still perform acylcarnitine profiling using LC-MS/MS based methodology that has remained almost unchanged for around 2 decades. This “classical” approach normally involves a direct infusion (no chromatographic separation) into the MS system following a butylation based sample derivatisation. Although this approach is still widely used today, improvement in LC-MS technology observed over the last 15 years such as UHPLC and higher sensitivity MS systems means that a non-derivatisation approach that can be more informative with a relatively rapid LC separation is feasible. |
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Topic(s): Metabolites & Metabolomics
Poster #20c View Map
Introduction:Transplantation is the treatment associated with increased survival rate and greater quality of patient’s life when compared to conventional dialysis. Even nowadays transplantology suffers from the lack of reliable methods of organ quality assessment. The standard protocols are limited to macroscopic appearance inspection or invasive tissue biopsy which do not provide a comprehensive information about the graft. Kidney is the organ largely associated with metabolic processes, thus measurements of metabolites concentrations may permit determining potential organ quality biomarkers and predicting the graft outcome. Hence, there is a need for new diagnostic solution allowing on site graft monitoring and quick decision-making processes during the surgery. |
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Topic(s): Metabolites & Metabolomics
Poster #22c View Map
Introduction: Liver transplant surgery is currently the standard of treatment in patients with end-stage organ failure. Nowadays, the dominant method of organ preservation used by most transplantation centers is the static cold storage (SCS). However, a better method of organ preservation is sought, which would allow extending the storage time of the graft while maintaining its proper quality The proposed method is normothermic ex-vivo liver perfusion (NEVLP), based on maintaining normal metabolic activity, which gives the opportunity to better assessment of liver viability before implantation. One of the possibilities is to assess the production of bile by the liver perfused in these conditions. It is considered that the production of bile alone is not sufficient evidence for the proper functioning of the liver and directs the research to assess the composition of bile. Therefore, it is assumed that changes in the concentration of bile acids, which are the main component of bile, may correlate with changes occurring in the transplanted organ. |
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Topic(s): Metabolites & Metabolomics
Poster #26a View Map
Introduction. In last few years multi-target drugs have gained high popularity at the drug development market. Its main pharmacological effect is provided by the combined action of hybrid compounds that interact with several targets in the area of one disease. Novel biogenic molecules, prostanit® and nitroproston®, represent an interesting example of multi-target compounds. They are based on natural prostaglandins PGE1 (in prostanit®) and PGE2 (in nitroproston®) linked by a glycerol moiety to two nitric oxide (NO) ‒ donating fragments. Due to biogenic nature of the these pharmaceuticals, as well as rapid integration of their active components into biochemical cycles, metabolism study becomes difficult. To overcome these complexities, metabolomic approaches were used, giving an opportunity to investigate their metabolic pathways, mechanisms of action and therapeutic effectiveness. |
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Topic(s): Metabolites & Metabolomics
Poster #26c View Map
Introduction |
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Topic(s): Metabolites & Metabolomics
Poster #26f View Map
Introduction: Since treatment advances for lysosomal storage disorders (LSDs), the application of mass spectrometry (MS) techniques have expanded to screening for some of the treatable LSDs. To date, flow injection MS (FI-MS) is generally the preferred screening technique to be of diagnostic value for 6 LSDs, namely Pompe, MPS-I, Fabry, Gaucher, Niemann-Pick A/B and Krabbe disorders, from a single dried blood spot (DBS) sample. We evaluated the analytical performance and diagnostic precision of a 6-plex LSD enzyme assay utilizing the technique of liquid chromatography with tandem MS (LC-MS/MS) within the clinical laboratory setting. |
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Topic(s): Metabolites & Metabolomics
Poster #27b View Map
Introduction: Early detection of diseases by newborn screening (NBS) is necessary for correct and timely clinical decisions. One of the early methods for NBS of phenylketonuria (PKU) was a fluorimetric method for quantification of phenylalanine (Phe). This method is still used in many countries in south-eastern Europe. The introduction of expanded NBS with tandem mass spectrometry (MS/MS) enabled screening for many diseases, including PKU. Slovenia is now in a unique position to compare the methods because it screens for PKU with a fluorimetric method detecting Phe and also using MS/MS for expanded NBS, also measuring Phe and tyrosine. |
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Topic(s): Metabolites & Metabolomics
Poster #27d View Map
INTRODUCTION: Inborn errors of metabolism related to biosynthesis and remodelling of phospholipids, sphingolipids is a newly emerging area in inherited metabolic disorders. Phospholipids are synthesized by a de-novo process, known as ‘‘Kennedy pathway’’ and are then dispersed asymmetrically by a remodeling process called ''Lands Cycle''.The MBOAT7, subject of the current study, is located in the Lands lipid remodeling pathway and inserts arachidonic acid to the sn-2 position of lysophosphotidylinositol. While there animal models of the MBOAT7 exist to elucidate its functional role, no study has yet been conducted on the effects of the MBOAT7 gene defect in humans. |
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Topic(s): Metabolites & Metabolomics
Poster #27g View Map
INTRODUCTION: The most dynamic process which regulates DNA methylation is recently discovered active demethylation. It involves ten-eleven translocation (TET) enzymes to catalyze stepwise oxidation of 5-methylcytosine (5-mCyt) to 5-hydroxymethylcytosine (5-hmCyt) and further demethylation products 5-formylcytosine (5-fCyt) and 5-carboxylcytosine (5-caCyt). Mutations targeting TET genes are frequently observed in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Mutations in genes: succinate dehydrogenase (SDH), fumarate hydratase (FH) and isocitrate dehydrogenase (IDH) are also found in acute leukemias. These mutations result in accumulation of the succinate (SA), fumarate (FA), 2-oxoglutarate (2-OG) and R-2-hydroxyglutarate (R-2HG). It may deregulate the activity of TET enzymes and, in turn, DNA demethylation. Although the oncogenic mechanism of these mutations remains still under investigation, determine of these metabolites could be relevant for diagnosis, prognosis and treatment of a subset of patients with AML and MDS. |
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Topic(s): Metabolites & Metabolomics
Poster #28f View Map
Introduction: Type 2 Diabetes (T2D), the most prevalent form of diabetes, is a metabolic disorder characterized by decreased insulin sensitivity and abnormal hepatic glucose production. Monitoring metabolic alterations during T2D progression may provide better understanding of its pathogenesis and identify potential biomarkers for early diagnosis. Several metabolomics approaches have been applied in diabetic research for identification of metabolites associated with the risk of T2D and related pathways. Here, a semi-targeted workflow was designed to confidently measure known metabolic differentiators, such as branched-chain amino acids, while allowing for the discovery of previously unidentified metabolites that are altered during T2D progression. This approach combines high resolution accurate mass Orbitrap™ technology for maximum detection of known and unknown metabolites in serum samples, with intelligence-driven fragmentation for the identification of knowns and structural elucidation of unknown biomarkers. |
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Topic(s): Metabolites & Metabolomics
Poster #20k View Map
Introduction |
