Science Of Metabolomics Research Articles

Integrative metabolomics science in Alzheimer's disease: Relevance and future perspectives.

Alzheimer's disease (AD) is determined by various pathophysiological mechanisms starting 10-25 years before the onset of clinical symptoms. As multiple functionally interconnected molecular/cellular pathways appear disrupted in AD, the exploitation of high-throughput unbiased omics sciences is critical to elucidating the precise pathogenesis of AD. Among different omics, metabolomics is a fast-growing discipline allowing for the simultaneous detection and quantification of hundreds/thousands of perturbed metabolites in tissues or biofluids, reproducing the fluctuations of multiple networks affected by a disease. Here, we seek to critically depict the main metabolomics methodologies with the aim of identifying new potential AD biomarkers and further elucidating AD pathophysiological mechanisms. From a systems biology perspective, as metabolic alterations can occur before the development of clinical signs, metabolomics - coupled with existing accessible biomarkers used for AD screening and diagnosis - can support early disease diagnosis and help develop individualized treatment plans. Presently, the majority of metabolomic analyses emphasized that lipid metabolism is the most consistently altered pathway in AD pathogenesis. The possibility that metabolomics may reveal crucial steps in AD pathogenesis is undermined by the difficulty in discriminating between the causal or epiphenomenal or compensatory nature of metabolic findings.

Recent Advances in Metabolomics and Therapeutics for Cancer Cachexia

Cancer Cachexia afflicts 50 - 80 percent of cancer patients with roughly 20 percent of all cancer patients dying of cachexia. Metabolomics is the study of different metabolites, their location in the body, and the timing of their appearance and disappearance. As a result, this science of Metabolomics can be applied to solve the problem of Cancer Cachexia. In this review, I examine recent studies on metabolism that use Metabolomics as their instrument of discovery. Further, this review details potential therapeutic interventions at the cellular, animal, and human level that show promise for attenuating Cancer Cachexia.

Microbiome and Metabolomics in Liver Cancer: Scientific Technology.

Primary liver cancer is a heterogeneous disease. Liver cancer metabolism includes both the reprogramming of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment and fluctuations in regular tissue metabolism. Currently, metabolomics and metabolite profiling in liver cirrhosis, liver cancer, and hepatocellular carcinoma (HCC) have been in the spotlight in terms of cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecules, chemicals, and metabolites. Metabolomics technologies can provide critical information about the liver cancer state. Here, we review how liver cirrhosis, liver cancer, and HCC therapies interact with metabolism at the cellular and systemic levels. An overview of liver metabolomics is provided, with a focus on currently available technologies and how they have been used in clinical and translational research. We also list scalable methods, including chemometrics, followed by pathway processing in liver cancer. We conclude that important drivers of metabolomics science and scientific technologies are novel therapeutic tools and liver cancer biomarker analysis.

Metabolomics and Chemoinformatics in Agricultural Biotechnology Research: Complementary Probes in Unravelling New Metabolites for Crop Improvement.

Simple SummaryThe world is facing an overarching threat to food security, particularly in developing nations. The issue is further exacerbated by the apparent impacts of biotic and abiotic stresses driving down crop yields and productivity. Conventional strategies to improve yields and sustain productivity have been employed, including plant breeding for favourable and resilient agronomic traits. However, the efficacy and success rates of these methods are declining, partly due to the rapid changes in climate variability and the emergence of new and resistant phytopathogens. Additionally, the process of creating new and improved transgenic varieties of crops is long and can be expensive. Thus, new and innovative technologies are required for crop improvement. This review explores recent advances in the science of metabolomics and chemoinformatics, which have presented an avenue for rapid and robust analysis; moreover, it explores the elucidation of the complex plant metabolome, providing the opportunity to decipher the reactionary mechanisms of plants to the surrounding environment through their metabolic activity. As such, specific metabolites can, thus, be selected as biomarkers for crop improvement based on their functional characteristics under varying environmental conditions (growth, development, and defence). This new knowledge can enhance breeding practices through rapid and robust metabolic engineering techniques for sustainable agriculture.The United Nations (UN) estimate that the global population will reach 10 billion people by 2050. These projections have placed the agroeconomic industry under immense pressure to meet the growing demand for food and maintain global food security. However, factors associated with climate variability and the emergence of virulent plant pathogens and pests pose a considerable threat to meeting these demands. Advanced crop improvement strategies are required to circumvent the deleterious effects of biotic and abiotic stress and improve yields. Metabolomics is an emerging field in the omics pipeline and systems biology concerned with the quantitative and qualitative analysis of metabolites from a biological specimen under specified conditions. In the past few decades, metabolomics techniques have been extensively used to decipher and describe the metabolic networks associated with plant growth and development and the response and adaptation to biotic and abiotic stress. In recent years, metabolomics technologies, particularly plant metabolomics, have expanded to screening metabolic biomarkers for enhanced performance in yield and stress tolerance for metabolomics-assisted breeding. This review explores the recent advances in the application of metabolomics in agricultural biotechnology for biomarker discovery and the identification of new metabolites for crop improvement. We describe the basic plant metabolomics workflow, the essential analytical techniques, and the power of these combined analytical techniques with chemometrics and chemoinformatics tools. Furthermore, there are mentions of integrated omics systems for metabolomics-assisted breeding and of current applications.

Metabolomics of peripheral artery disease.

The science of metabolomics has emerged as a novel tool for studying changes in metabolism that accompany different disease states. Several studies have applied this evolving field to the study of various cardiovascular disease states, which has led to improved understanding of metabolic changes that underlie heart failure and ischemic heart disease. A significant amount of progress has also been made in the identification of novel biomarkers of cardiovascular disease. Another common atherosclerotic disease, peripheral artery disease (PAD) affects arteries of the lower extremities. Although certain aspects of the disease pathophysiology overlap with other cardiovascular diseases in general, PAD patients suffer unique manifestations that lead to significant morbidity and mortality as well as severe functional limitations. Furthermore, because over half of PAD patients are asymptomatic, there is a need for improved diagnostic and screening methods. Identification of metabolites associated with the disease may thus be a promising approach for PAD. However, PAD remains highly understudied. In this chapter, we discuss the application of metabolomics to the study of PAD.

Metabolomics and its role in plant pathology

Metabolomics is one of the most eminent and newly emerging omic sciences. It is a powerful tool to study metabolic changes that occur in an organism. Plants produce a wide range of metabolites and the study of these metabolites can answer a number of questions that arise in the minds of researchers. Change in the metabolites is the most important feature in a genetically modified plant or plant interactions with pests, pathogens and the environment. Plant pathogen interactions are amongst the most biochemically complex mechanisms and pose a great challenge in front of plant pathologists; metabolomics not only play a great role in deciphering these complex interactions but also the study of certain defence-related metabolic changes can be utilized in a number of ways to protect the plant from the harmful pathogens. The science of metabolomics utilizes a number of techniques to study the wide variety of metabolites. This review will give a brief about the various techniques used in metabolomics and how some of these techniques have been successfully utilized in the field of plant pathology.

The role of urine metabolomics among newborn infants with hypoxic ishaemic encephalopathy: a literature review

Background: Perinatal asphyxia (PA) which may result in hypoxic ischaemic encephalopathy (HIE) affects four million neonates worldwide and accounts for the death of one million of affected babies. The science of metabolomics has become an area of growing interest in neonatal research, with a potential role in identifying useful biomarkers that can accurately predict injury severity in perinatal asphyxia and HIE. The aim of this review is to look at the evidence of the usefulness of urine metabolomics in predicting outcome in PA/HIE. Methods: The key words used in the advanced search ‘urine metabolomics’ AND ‘perinatal asphyxia’ OR ‘hypoxic ischaemic encephalopathy’, yielded 13 articles. Results: Of the selected thirteen studies, 38% (n = 5) were human studies, 31% (n= 4) were animal studies and 31% (n = 4) were review articles. The studies confirmed the involvement of known pathways in the development of PA/HIE, primarily the Krebs cycle evidenced by accumulation of TCA cycle intermediates (citrate, α-ketoglutarate, succinate) and anaerobic pathways indicated by increased lactate. Other pathways involved include amino acid and carbohydrate pathways. Conclusion: Metabolomic studies so far are promising in highlighting potential biomarker profiles in PA/HIE. Further research is necessary to further clarify the role of identified metabolites in predicting outcome and prognosis in neonates affected by PA/HIE.

You Are What You Eat: Application of Metabolomics Approaches to Advance Nutrition Research.

A healthy condition is defined by complex human metabolic pathways that only function properly when fully satisfied by nutritional inputs. Poor nutritional intakes are associated with a number of metabolic diseases, such as diabetes, obesity, atherosclerosis, hypertension, and osteoporosis. In recent years, nutrition science has undergone an extraordinary transformation driven by the development of innovative software and analytical platforms. However, the complexity and variety of the chemical components present in different food types, and the diversity of interactions in the biochemical networks and biological systems, makes nutrition research a complicated field. Metabolomics science is an “-omic”, joining proteomics, transcriptomics, and genomics in affording a global understanding of biological systems. In this review, we present the main metabolomics approaches, and highlight the applications and the potential for metabolomics approaches in advancing nutritional food research.

Ketosis an Old Story Under a New Approach

Ketosis, characterized by high concentrations of ketone bodies in the blood, urine, and milk, affects a considerable number of cows immediately after calving. Although much is known about ketosis, dairy cows continue to be affected in every herd world-wide. Cows affected by ketosis are treated with palliative treatments after the disease is diagnosed. This is a very expensive approach and costs the dairy industry extra expenses, contributing to lower profitability of dairy herds. In this review article, we summarize the mainstream view on ketosis, classification of ketosis into three types, current diagnostic approaches to ketosis, and the economic impact of ketosis on dairy farms. Additionally, we discuss the most recent applications of the new ‘omics’ science of metabolomics in studying the etiopathology of ketosis as well as its contribution in identification of novel screening or diagnostic biomarkers of ketosis.

Prospek Kontrasepsi Pria dalam Pengendalian Pertumbuhan Penduduk melalui Pendekatan Molekular

Nowadays, developing contraception methods were mostly addressed to women. The development of male contraception was still limited. There were condoms, vasectomies, and interrupted intercourse, which used in male contraception. The condom method and interrupted intercourse have a high failure rate and inconvenience in its use. The vasectomy method is invasive and expensive. The development of molecular-based contraceptive methods with minimal impacts on health is expected to be a good breakthrough in the context of population control and improving the quality of health. The study aims to summarize and analyze the early development of contraception until the invention of molecular contraception through immunologic, proteomic, and metabolomics science. This article review was done by studying literature in the PubMed Central (PMC), Springer, and Open Access ScienceDirect databases. The search was performed with the keywords "Contraception", "Molecular Contraception", "Male Contraception", and "Immunocontraception". Journal articles that fit the theme of the review are then reviewed by paraphrasing the core of the research. The conclusion drawn from the review is that male contraception using the molecular method is still being developed at a pre-clinical experimental stage using animal laboratory technique and in vitro technique. The key to the success of this molecular method is that the more specific the molecular target at male fertility levels, the better of contraceptive effect. The molecular- based contraception is expected to be a breakthrough in terms of population control that have more effective, safe, and comfortable, especially for male contraception

Untargeted metabolomic profiling of urine from healthy dogs and dogs with chronic hepatic disease.

Chronic hepatic disease can present a diagnostic challenge with different etiologies being associated with similar clinical and laboratory findings. The histopathological assessment of a liver biopsy specimen is usually required in order to make a definitive diagnosis and the availability of non-invasive prognostic biomarkers is limited. The emerging science of metabolomics is used to detect changes in endogenous low molecular weight metabolites in biological samples and offers the possibility of identifying noninvasive markers of disease. The objective of this study was to investigate differences in the urine metabolome between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Stored urine samples from 10 healthy dogs, 10 dogs with chronic hepatitis, 6 dogs with hepatocellular carcinoma, and 5 dogs with a congenital portosystemic shunt were analyzed. The urine metabolome was analyzed by gas chromatography–quadrupole time of flight mass spectrometry and 220 known metabolites were identified. Principal component analysis and heat dendrogram plots of the metabolomics data showed clustering between groups. Random forest analysis showed differences in the abundance of various metabolites including putrescine, gluconic acid, sorbitol, and valine. Based on univariate statistics, 37 metabolites were significantly different between groups. In, conclusion, the urine metabolome varies between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Further targeted assessment of these metabolites is needed to assess their diagnostic utility.

Relationship of clinical efficacy of glucose lowering agents, gut microbiota, diet, and patient’s genotype in diabetes mellitus type 2

The review is devoted to revealing the connection between the intestinal microflora, diet and the effectiveness of glucose – lowering therapy in patients with type 2 diabetes. Potential targets and the effects of oral and injectable hypoglycemic agents on microbiota in this category of patients are considered. The work reflects modern views on hypoglycemic drugs from the standpoint of the science of metabolomics within the framework of personalized medicine.

SistematX, an Online Web-Based Cheminformatics Tool for Data Management of Secondary Metabolites.

The traditional work of a natural products researcher consists in large part of time-consuming experimental work, collecting biota to prepare and analyze extracts and to identify innovative metabolites. However, along this long scientific path, much information is lost or restricted to a specific niche. The large amounts of data already produced and the science of metabolomics reveal new questions: Are these compounds known or new? How fast can this information be obtained? To answer these and other relevant questions, an appropriate procedure to correctly store information on the data retrieved from the discovered metabolites is necessary. The SistematX (http://sistematx.ufpb.br) interface is implemented considering the following aspects: (a) the ability to search by structure, SMILES (Simplified Molecular-Input Line-Entry System) code, compound name and species; (b) the ability to save chemical structures found by searching; (c) compound data results include important characteristics for natural products chemistry; and (d) the user can find specific information for taxonomic rank (from family to species) of the plant from which the compound was isolated, the searched-for molecule, and the bibliographic reference and Global Positioning System (GPS) coordinates. The SistematX homepage allows the user to log into the data management area using a login name and password and gain access to administration pages. In this article, we introduced a modern and innovative web interface for the management of a secondary metabolite database. With its multiplatform design, it is able to be properly consulted via the internet and managed from any accredited computer. The interface provided by SistematX contains a wealth of useful information for the scientific community about natural products, highlighting the locations of species from which compounds are isolated.

HMDB 4.0: the human metabolome database for 2018.

The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards. This year's update, HMDB 4.0, represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB’s chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC–MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.

Metabolome Comparison of Bioactive and Inactive Rhododendron Extracts and Identification of an Antibacterial Cannabinoid(s) from Rhododendron collettianum.

The science of metabolomics offers the possibility to measure full secondary plant metabolomes with limited experimental effort to allow identification of metabolome differences using principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) of liquid chromatography mass spectrometry (LC-MS) data. To demonstrate a bioinformatics driven hypothesis generator for identification of biologically active compounds in plant crude extracts, which is validated by activity guided fractionation. Crude extracts of Rhododendron leaves were tested for their antibacterial activity using agar diffusion and minimum inhibitory concentration assays. Extracts were profiled by LC-MS. PCA and PLS-DA were used for differentiation of bioactive and inactive extracts and their metabolites. Preparative-high performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) spectroscopy were used for separation and structure elucidation of pure compound(s) respectively. An antibacterial Rhododendron collettianum was compared to a series of inactive extracts. Three metabolites were found to distinguish R. collettianum from other species indicating the ability of PCA and PLS-DA to suggest potential bioactive substances. An activity-guided fractionation of R. collettianum extracts was carried out and cannabiorcichromenic acid (CCA) was identified as antibacterial compound thereby validating the PCA and PLS-DA generated hypothesis. Four mammalian cell lines were used to estimate possible cytotoxicity of CCA. It was shown that bioinformatics tools facilitate early stage identification of a biologically active compound(s) using LC-MS data, which reduce complexity and number of separation steps in bioactive screening. Copyright © 2017 John Wiley & Sons, Ltd.

Training needs in metabolomics.

Metabolomics has come of age and is predicted to have a compound annual growth rate of 30 % from 2014 to 2019 and a market value of $2.1 billion by 2019 (Rohan 2014). While recent progress has been driven by technological advances in both analytical instrumentation and software, and by the availability of ring-fenced research funding in some countries, insufficient attention has focused on developing the specialist training required to support this growth. The international Metabolomics Society was established to promote the growth of this field (Goodacre 2005), to stimulate collaboration among scientists in academia, government and industry, and to deliver conferences and training workshops. ELIXIR-UK (http://elixir-uk.org/) is the United Kingdom node within the European ELIXIR infrastructure and currently focuses on bioinformatics training provision that will be delivered in specialised centres, through face-to-face courses and e-learning; this training will be in partnership with other European ELIXIR Nodes. To guide the development (and ultimately provision) of fit-for-purpose training, considering factors such as scientific content, expertise levels of attendees, knowledge level of course, and mechanisms by which to provide the training, the international Metabolomics Society and ELIXIR-UK have jointly conducted a global assessment of the training needs in metabolomics science. Specifically, a questionnaire was developed and widely distributed to determine the training needs of our international community, the training programs that already exist, the new course content to develop and the mechanisms by which this training could be delivered. By “metabolomics science”, we include the underpinning science and technology (experimental design, analytical measurements, computational analyses and informatics) and any field of application from microbes to plants and animals, including humans. Here we report the results of the training needs questionnaire, from which we have derived a series of key recommendations to support the training of the growing metabolomics community. By sharing the full results, we hope that others will conduct additional analyses and be able to derive further interesting conclusions, and collectively help to guide the development of metabolomics training programs globally.

Activity update from the early career members network

Established by the Metabolomics Society, 2014 saw the Early Members Network (EMN) celebrate its first birthday. Initially run by nine early career researchers, forming the EMN-committee, the official EMN mission was to recognize the value and importance of early career members, to ensure that their views are heard and acted upon, ultimately improving their experience of metabolomics science and the community as a whole (Putri 2014). Dedicated to all Metabolomics Society members who are within 5 years of completing their higher degrees, the EMN has started to make significant strides to achieve its vision to establish a real sense of community and engagement between early career researchers globally through leading initiative and enthusiastic appearance. Past activities of 2014

Meeting report from "Frontiers in Nutritional Science: Nutritional Metabolomics".

The potential for transforming nutritional and health research through the discovery and application of non-invasive markers of dietary intake and metabolic status is profound. The science of metabolomics for the fingerprinting of volatile organic compounds (VOCs) from expired human breath holds great promise in this regard. Coupled with tools utilising sensor technology, breath volatile signatures allow a new horizon of research in which indicators of metabolic risk and indicators of dietary intake could be collected at a population level with unprecedented simplicity and low cost. Metabolomics (measuring metabolites from physiological process) provides a “window into the body”, which could transform how we measure health, how we identify and monitor people most at risk of disease and the way we monitor food intake. [...]

Tu1763 Nuclear Magnetic Resonance (NMR)-Base Urine Metabolomics Analysis of Patients With Clostridium difficile Infection

Background: Clostridium difficile infection (CDI) is a common hospital acquired infections with significant morbidity and mortality. The risk of recurrent CDI is approximately 20%, 40% and up to 80% after the first, second, and third episode, respectively. Furthermore, recurrent CDI is associated with intestinal dysbiosis, characterized by reduced biodiversity and expansion of potentially pathogenic bacteria. The novel science of metabolomics provides a powerful tool to characterize vast numbers of metabolites in biological fluids with complex compositions and has recently yielded several clinically important diagnostic tests in cases where the human intestinal microbiota is altered. Aim: the aim of this pilot project was to examine the urine metabolomics profile in patients with CDI to determine if a unique metabolic profile was associated with recurrent infections. Method: Spot urine samples were prospectively collected from 31 patients (male 19, mean age 55 years) with CDI: 12 during 1st episode, 5 during 2nd episode, 5 during 3rd episode, and 9 with > 4th episode. Onedimensional NMR spectra were acquired using an Oxford 600MHz NMR instrument with a VNMRJ software. The 1H NMR spectrum of each urine sample was analyzed using Chenomx NMRSuite v7.6 (Chenomx Inc., Edmonton, AB). Multivariate statistical analysis was performed by using Simca P+ v 12.0.1 from Umetrics (Uema, Sweden). Results: Using 69 metabolites, a two-component orthogonal partial least squares (OPLS) model for 1, 2, 3 or at least 4 episodes of CIDwas built, with R2Y= 0.471 andQ2= 0.12 (model's predictability of data in 7-fold cross validation). Based on OPLS model, clustering was observed among patients with 1 episode, 2 episodes and 3 or more episodes of CDI, respectively as shown in figure 1. Conclusion: This is the first study to demonstrate that NMR urine metabolomics has the ability to distinguish patients with various frequencies of recurrent CDI. Urine metabolomics has the potential to become an accurate, noninvasive and inexpensive diagnostic test for predicting recurrent CDI, and can help clinicians in risk stratification and selection of the most appropriate therapy for each patient.

Metabolomics for the practising vet

Imagine a world with no mystery illnesses, no diagnoses of exclusion and happy owners. Realistically, this is unlikely to happen in our lifetime. However, the promising new science of metabolomics...