DOCSLIB.ORG

Metabolomics for Biomarker Discovery: Key Signatory Metabolic Profiles

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Metabolomics for Biomarker Discovery: Key Signatory Metabolic Profiles H OH metabolites OH Article Metabolomics for Biomarker Discovery: Key Signatory Metabolic Profiles for the Identification and Discrimination of Oat Cultivars Chanel J. Pretorius, Fidele Tugizimana , Paul A. Steenkamp , Lizelle A. Piater and Ian A. Dubery * Research Centre for Plant Metabolomics, Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park, Johannesburg 2006, South Africa; [email protected] (C.J.P.); [email protected] (F.T.); [email protected] (P.A.S.); [email protected] (L.A.P.) * Correspondence: [email protected]; Tel.: +27-11-5592401 Abstract: The first step in crop introduction—or breeding programmes—requires cultivar identifica- tion and characterisation. Rapid identification methods would therefore greatly improve registration, breeding, seed, trade and inspection processes. Metabolomics has proven to be indispensable in interrogating cellular biochemistry and phenotyping. Furthermore, metabolic fingerprints are chemi- cal maps that can provide detailed insights into the molecular composition of a biological system under consideration. Here, metabolomics was applied to unravel differential metabolic profiles of various oat (Avena sativa) cultivars (Magnifico, Dunnart, Pallinup, Overberg and SWK001) and to identify signatory biomarkers for cultivar identification. The respective cultivars were grown under controlled conditions up to the 3-week maturity stage, and leaves and roots were harvested for each cultivar. Metabolites were extracted using 80% methanol, and extracts were analysed on an ultra-high Citation: Pretorius, C.J.; Tugizimana, performance liquid chromatography (UHPLC) system coupled to a quadrupole time-of-flight (qTOF) F.; Steenkamp, P.A.; Piater, L.A.; high-definition mass spectrometer analytical platform. The generated data were processed and Dubery, I.A. Metabolomics for analysed using multivariate statistical methods. Principal component analysis (PCA) models were Biomarker Discovery: Key Signatory computed for both leaf and root data, with PCA score plots indicating cultivar-related clustering of Metabolic Profiles for the the samples and pointing to underlying differential metabolic profiles of these cultivars. Further Identification and Discrimination of Oat Cultivars. Metabolites 2021, 11, multivariate analyses were performed to profile differential signatory markers, which included car- 165. https://doi.org/10.3390/ boxylic acids, amino acids, fatty acids, phenolic compounds (hydroxycinnamic and hydroxybenzoic metabo11030165 acids, and associated derivatives) and flavonoids, among the respective cultivars. Based on the key signatory metabolic markers, the cultivars were successfully distinguished from one another in Academic Editor: Gilles Comte profiles derived from both leaves and roots. The study demonstrates that metabolomics can be used as a rapid phenotyping tool for cultivar differentiation. Received: 15 February 2021 Accepted: 5 March 2021 Keywords: Avena sativa; cultivar distinction; liquid chromatography; mass spectrometry; metabolomics; Published: 12 March 2021 multivariate data analysis; oat; secondary metabolites Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- 1. Introduction iations. Food demand has been rapidly increasing with the overall growth in the world pop- ulation, which is expected to reach around 9.7 billion by the year 2050 [1]. Now more than ever, crop improvement and plant breeding studies have become imperative in en- suring food security and sustainability [2]. The primary step involved in plant breeding, Copyright: © 2021 by the authors. inspection, registration, trade and seed production requires the identification of cultivars Licensee MDPI, Basel, Switzerland. and varieties, and therefore a rapid and effective method for cultivar fingerprinting is This article is an open access article required [3]. Over the years, plant breeding has been greatly improved for unravelling the distributed under the terms and conditions of the Creative Commons molecular basis of complex traits using genomic analyses and next-generation sequencing Attribution (CC BY) license (https:// methods [4]. Currently, plant breeding methods have integrated phenotypic traits with creativecommons.org/licenses/by/ a range of marker-assisted selection techniques to more efficiently determine trait out- 4.0/). comes [5]. Although genetic markers have been at the forefront of plant breeding efforts, Metabolites 2021, 11, 165. https://doi.org/10.3390/metabo11030165 https://www.mdpi.com/journal/metabolites Metabolites 2021, 11, 165 2 of 23 many limitations have restricted the use thereof in analysing complexities arising from genotype × environment interactions (environmental plasticity), polygenic inheritance and epistasis (which is referred to as the action of one gene on another) [6]. Metabolomics, a systems biology approach to interrogate cellular biochemistry and metabolism, offers unique possibilities that can be incorporated into unravelling these complexities to gain a genotype × metabolite × phenotype understanding that can be applied in plant breeding. The phenotype is an observable reflection that results from complex interactions between the genotype and the environment, with the former also able to prime multiple phenotypes [7]. These interactions can result in various success rates in reproduction and cause subsequent alterations in the genotype, as summarised in the abridged illustration (Figure1). To bridge the gap between the genotype and phenotype, Metabolites 2021, 11, x FOR PEER REVIEW 3 of 25 metabolomics was proposed as a means to provide insight into how genotypic variation affects phenotypic diversity in plants [8–10]. FigureFigure 1.1. Triangular arrangement illustrating illustrating the the genoty genotypepe × ×environmentenvironment × phenotype× phenotype interactions, interactions, with the metabolome at the core, bridging the gap between the genotype and phenotype. The metab- with the metabolome at the core, bridging the gap between the genotype and phenotype. The olome is the final recipient of biological information flow and carries imprints of genetic and envi- metabolomeronmental factors. is the It final is more recipient sensitive of biological to perturba informationtions in both flow metabolic and carries fluxes imprintsand enzyme of geneticactivity and environmentalthan either the transcriptome factors. It is more or proteome sensitive and to is perturbations thus a reflection in both of the metabolic phenotype. fluxes Quantitative, and enzyme activityglobal measurements than either the of transcriptome the metabolome or proteome therefore andprovide is thus an aexploration reflection ofof the cellular phenotype. metabolism, Quantita- tive,revealing global patterns measurements and functional of the metabolome signatures of therefore the biochemical provide landscape an exploration and cellular of cellular physiology metabolism, revealingof the system patterns under and consideration functional signatures[8–10]. of the biochemical landscape and cellular physiology of the system under consideration [8–10]. 2. Results 2.1. DifferentialMetabolomics, Chromatographic–Mass defined as the comprehensive Spectrometric Analyses qualitative of Respective and quantitative Oat Cultivars analysis of allMethanolic metabolites extracts in a biological of leaf and system, root tissue is ans of established the respective omics cultivars technology were separated that holds promiseon an ultra-high in agricultural performance research; liquid therefore, chromatography metabolomics system has becomecoupled an to indispensable a quadrupole tool intime-of-flight various plant high-definition sciences studies mass [11 ,12spectr]. Dueometer to the (UHPLC–qTOF–MS) diverse and large variety and detected of metabolites in foundboth positive in plants, and an negative extensive electrospray array of analytical ionisation techniques(ESI) modes. has Initial been optimisation developed tostud- obtain sufficienties indicated coverage that the for majority plant metabolomics. of extractable metabolites Liquid chromatography–mass ionised more effectively spectrometry in the (LC–MS)-basedESI (−) mode; accordingly, plant metabolomics, only these compareddatasets are to further that of presented gas chromatography–mass and illustrated. The spec- trometrychromatographically (GC–MS) and distinct nuclear base magnetic peak intensity resonance (BPI) (NMR),chromatograms has been of advantageousleaf and root in detectingextracts (Figure a wide 2A,B) range provide of secondary a visual presenta metabolitestion/description with higher of sensitivitythe similarities and and selectivity dif- ferences between the respective cultivars and reflect the complexity of their metabolic profiles. Although chromatography is extremely useful in separating the components based on their polarity, and high-definition mass spectrometry enables accurate mass de- termination in order to generate empirical formulae to aid in compound annotation, fur- ther chemometric analyses were performed to obtain biologically useful information. Metabolites 2021, 11, 165 3 of 23 (compared to NMR) and has the ability to detect and identify a broader range of com- pounds whilst being less time-consuming in the preparation of samples (compared to GC–MS which requires derivatisation) [13–15]. In the past, metabolomics has proven crucial for studying plant x environment interac- tions (e.g., adaptive responses towards biotic and abiotic stresses) and
Load more

Recommended publications
  • Technical Considerations and Protocol Optimization for Neonatal Salivary Biomarker Discovery and Analysis
    PERSPECTIVE published: 26 January 2021 doi: 10.3389/fped.2020.618553 Technical Considerations and Protocol Optimization for Neonatal Salivary Biomarker Discovery and Analysis Elizabeth Yen 1,2, Tomoko Kaneko-Tarui 1 and Jill L. Maron 1,2* 1 Mother Infant Research Institute at Tufts Medical Center, Boston, MA, United States, 2 Division of Newborn Medicine, Tufts Children’s Hospital, Boston, MA, United States Non-invasive techniques to monitor and diagnose neonates, particularly those born prematurely, are a long-sought out goal of Newborn Medicine. In recent years, technical advances, combined with increased assay sensitivity, have permitted the high-throughput analysis of multiple biomarkers simultaneously from a single sample source. Multiplexed transcriptomic and proteomic platforms, along with more comprehensive assays such as RNASeq, allow for interrogation of ongoing physiology and pathology in unprecedented ways. In the fragile neonatal population, saliva is an ideal biofluid to assess clinical status serially and offers many advantages over more Edited by: invasively obtained blood samples. Importantly, saliva samples are amenable to analysis Diego Gazzolo, SS Annunziata Polyclinic Hospital, on emerging proteomic and transcriptomic platforms, even at quantitatively limited Chieti, Italy volumes. However, biomarker targets are often degraded in human saliva, and as a mixed Reviewed by: source biofluid containing both human and microbial targets, saliva presents unique Anne Lee Solevåg, challenges for the investigator. Here, we provide insight into technical considerations Akershus University Hospital, Norway Trent E. Tipple, and protocol optimizations developed in our laboratory to quantify and discover neonatal University of Oklahoma Health salivary biomarkers with improved reproducibility and reliability. We will detail insights Sciences Center, United States learned from years of experimentation on neonatal saliva within our laboratory ranging *Correspondence: Jill L.
    [Show full text]
  • Exploring the Transcriptome for Novel Biomarker Discovery AMP-AD Biomarker Pilot Study
    Exploring the transcriptome for novel biomarker discovery AMP-AD Biomarker Pilot Study Nilüfer Ertekin-Taner, MD, PhD Professor of Neurology and Neuroscience Mayo Clinic Florida Spring ADC Meeting May 2nd, 2019 ©2016 MFMER | slide-1 AMP-AD Team Mayo Clinic Florida Banner Sun Health Nilüfer Ertekin Taner, MD, PhD Tom Beach, MD Steven G. Younkin, MD, PhD Dennis Dickson, MD New York Genomics Center (WGS) Minerva Carrasquillo, PhD Mariet Allen, PhD Mayo Clinic Genomics Core Joseph Reddy, PhD Bruce Eckloff (RNASeq) Xue Wang, PhD Julie Cunningham, PhD (GWAS) Kim Malphrus Thuy Nguyen Mayo Clinic Bioinformatics Core Sarah Lincoln Asha Nair, PhD University of Florida Mayo Clinic Epigenomics Development Todd Golde, MD, PhD. Laboratory Jada Lewis, Ph.D. Tamas Ordog, MD Paramita Chakrabarty, PhD Jeong-Hong Lee, PhD Yona Levites, PhD Mayo Clinic IT Institute for Systems Biology Andy Cook Nathan Price, PhD Curt Younkin Cory Funk, PhD Hongdong Li, PhD Mayo Clinic Study of Aging Paul Shannon Ronald Petersen, MD, PhD *AMP-AD consortium* ©2016 MFMER | slide-2 Overarching Goal A System Approach to Targeting Innate Immunity in AD (U01 AG046193) To identify and validate targets within innate immune signaling, and other pathways that can provide disease- modifying effects in AD using a multifaceted systems level approach. ©2016 MFMER | slide-3 AMP-AD Phase I Original Aim 1: To detect Original Aim 2: To assess AD Original Aim 3: To Original Aim 4: To transcript alterations in innate risk conferred by variants in manipulate innate determine outcome of immunity genes in mice and innate immunity genes from immune states in gene manipulation in humans.
    [Show full text]
  • Emerging Role and Recent Applications of Metabolomics Biomarkers in Obesity Disease Cite This: RSC Adv.,2017,7, 14966 Research
    RSC Advances View Article Online REVIEW View Journal | View Issue Emerging role and recent applications of metabolomics biomarkers in obesity disease Cite this: RSC Adv.,2017,7, 14966 research Aihua Zhang,a Hui Suna and Xijun Wang*ab Metabolomics is a promising approach for the identification of metabolites which serve for early diagnosis, prediction of therapeutic response and prognosis of disease. Obesity is becoming a major health concern in the world. The mechanisms underlying obesity have not been well characterized; obviously, more sensitive biomarkers for obesity diseases are urgently needed. Fortunately, metabolomics – the systematic study of metabolites, which are small molecules generated by the process of metabolism – has been important in elucidating the pathways underlying obesity-associated co-morbidities. The endogenous metabolites have key roles in biological systems and represent attractive candidates to understand obesity phenotypes. Novel metabolite markers are crucial to develop diagnostics for obesity related metabolic disorders. Received 26th December 2016 Creative Commons Attribution 3.0 Unported Licence. Metabolomics allows unparalleled opportunities to seize the molecular mechanisms of obesity and Accepted 28th February 2017 obesity-related diseases. In this review, we discuss the current state of metabolomic analysis of obesity DOI: 10.1039/c6ra28715h diseases, and also highlight the potential role of key metabolites in assessing obesity disease and explore rsc.li/rsc-advances the interrelated pathways. 1. Introduction
    [Show full text]
  • Apply Proteomic Approaches to Biomarker Discovery Proteomics for Biomarker Discovery
    Apply Proteomic Approaches to Biomarker Discovery Proteomics for Biomarker Discovery Why is it important to discover biomarkers? Biomarkers are biological substances that can be measured and quantified as indicators for objective assessment of physiological processes, therapeutic outcomes, environmental exposure, or pharmacologic responses to a certain drug. Biomarker discovery has many excellent outcomes: ◆ Provides specific information about the ◆ Allows clinicians to predict or monitor presence of a certain disease or disease stage. drug efficacy. ◆ Allows researchers to evaluate the safety or ◆ Confirms a drug’s pharmacological or efficacy of a particular drug in development. biological mechanism of action and helps minimize the safety risks. Figure 1. Potential use of biomarkers. Proteomics in biomarker discovery Typical molecular biomarkers include proteins, genetic mutations, aberrant methylation patterns, abnormal transcripts, miRNAs, and other biological molecules. Protein biomarkers are considered to be reliable indicators of the disease state and clinical outcome as they are the endpoint of biological processes. Remarkable innovations in proteomic technologies in the last years have greatly accelerated the process of biomarker discovery. 45-1 Ramsey Road, Shirley, NY 11967, USA www.creative-proteomics.com Tel: 1-631-275-3058 Fax: 1-631-614-7828 Email: [email protected] Proteomics for Biomarker Discovery ◆ Proteomes and proteomics Proteomes represent the network of interactions between genetic background and environmental factors. They may be considered as molecular signatures of disease, involving small circulating proteins or peptide chains from degraded molecules in various disease states. Proteomics is the study of the proteome including protein identification and quantification, and detection of protein-protein or protein-nucleic acid interactions, and post-translational modifications.
    [Show full text]
  • Metabolomics to Provide Biomarkers and Mechanistic Insights
    RTI International Metabolomics to Provide Biomarkers and Mechanistic Insights Susan Sumner, PhD Director NIH Eastern Regional Comprehensive Metabolomics Resource Core Systems and Translational Sciences Program RTI International [email protected] www.rti.org\rcmrc 919-541-7479 RTI International is a trade name of Research Triangle Institute. www.rti.org RTI International About RTI International . RTI is an independent not-for-profit research institute established in 1958 in Research Triangle Park, NC. RTI’s mission is to improve the human condition by turning knowledge into practice. RTI has 9 offices in the United States, 8 offices worldwide, and has projects in more than 40 countries. RTI is staffed with more than 4,000 employees working in health and pharmaceuticals, laboratory and chemistry services, advanced technology, statistics, international development, energy and the environment, education and training, and surveys. RTI has more than 800,000 square feet (ft2) of laboratory and office facilities in RTP, NC. The metabolomics facility in the Research Triangle Park consists of ~22,000 ft2 laboratory space. RTI International Metabolomics . Metabolomics involves the broad spectrum analysis of the low molecular weight complement of cells, tissues, or biological fluids. Metabolomics makes it feasible to uniquely profile the biochemistry of an individual, or system, apart from, or in addition to, the genome. – Metabon(l)omics is used to determine the pattern of changes (and related metabolites) arising from disease, dysfunction, disorder, or from the therapeutic or adverse effects of xenobiotics; including applications in plant and mammalian studies. This leading-edge method is now coming to the fore to reveal biomarkers for the early detection and diagnosis of disease, to monitor therapeutic treatments, and to provide insights into biological mechanisms.
    [Show full text]
  • Biomarker Discovery Comprehensive Crownbio’S Programs
    Biomarker Discovery Increase your success rate by bridging discovery knowledge to clinical results Gain in-depth biological insights and make RATE data-informed trial decisions through Biomarker haracolo stud to Discovery. De-risk therapeutic development by assess and confir oA identifying robust and sensitive biomarkers early in drug development. Maximize your clinical success rate by incorporating biomarkers into your drug development programs. CrownBio’s comprehensive Biomarker Discovery enables you to: BUILD • Corroborate clinical-preclinical data. Statistical odels to interret haracolo data • Evaluate the predictive value of potential biomarkers. • Identify genomic and proteomic signatures corresponding to treatment response. • Rescue previously ‘unsuccessful’ drugs. • Improve patient stratification. Discover and validate biomarkers through our integrated platform encompassing: SCR AATE • Portfolio of well-characterized in vivo, ex vivo, and in vitro models as Hothesis ree ioarer discovery reliable, clinically relevant test systems for functional and efficacy evaluation. • Comprehensive menu of validated genomic and proteomic assays to understand drug MoA. • Extensive datasets collected over decades of research covering thousands of models, including growth curves, sequencing data, and pharmacological data including mouse clinical trials. • Proprietary bioinformatics solutions using in-house and public datasets OPTIMIZE enabling systematic analysis of genomics and proteomics. Clinical trial desin • Expert in-house team to assist with experimental design, high complexity analyses, and result interpretation. Contact Sales Schedule Scientific Consultation Additional Resources 1.0 Version US: +1.855.827.6968 Request a consultation to discuss Read supporting publications, white UK: +44 (0)870 166 6234 your project. papers, watch presentations, and more. [email protected] [email protected] crownbio.com/resources +1.855.827.6968 | [email protected] | www.crownbio.com.
    [Show full text]
  • Proteomic and Genomic Technologies for Biomarker Discovery Where Are the Biomarkers? Vathany Kulasingam and Eleftherios P
    02_Diamandis_Editorial_1.qxd 11/21/06 3:06 PM Page 5 Clinical Proteomics Copyright © 2006 Humana Press Inc. All rights of any nature whatsoever are reserved. ISSN 1542-6416/06/02:05–12/$30.00 (Online) Editorial Proteomic and Genomic Technologies for Biomarker Discovery Where Are the Biomarkers? Vathany Kulasingam and Eleftherios P. Diamandis* Laboratory Medicine and Pathobiology, University of Toronto,Toronto, ON, Canada and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave.,Toronto, ON M5G 1X5, Canada Introduction cancer, as it is a model disease for studying such applications. Recently, we have witnessed the emer- gence of the “-omics” era with proteomics, Current Cancer Biomarkers peptidomics, degradomics, metabolomics, fractionomics, transcriptomics, interactomics, Despite tremendous progress in our under- and so forth. However, the only “-omics” standing of the molecular basis of many dis- other than genomics to become a “buzz- eases, cancer continues to be a major cause of word” is proteomics, a term used for studying morbidity and mortality among men and the proteome of an organism. With the com- women. There is convincing evidence that early pletion of the Human Genome Project, opti- detection of cancer can lead to better patient mistic views were expressed that novel outcomes through early administration of disease-specific biomarkers will be discov- therapy (1). Also, better clinical outcomes can ered through various high-throughput tech- be achieved with individualized treatments, niques, such as microarrays and mass which are more effective in subgroups of spectrometry (MS). Did the current technolo- patients, rather than in the total patient popu- gies deliver the goods? In the following, we lation.
    [Show full text]
  • Natural Products (Secondary Metabolites)
    Biochemistry & Molecular Biology of Plants, B. Buchanan, W. Gruissem, R. Jones, Eds. © 2000, American Society of Plant Physiologists CHAPTER 24 Natural Products (Secondary Metabolites) Rodney Croteau Toni M. Kutchan Norman G. Lewis CHAPTER OUTLINE Introduction Introduction Natural products have primary ecological functions. 24.1 Terpenoids 24.2 Synthesis of IPP Plants produce a vast and diverse assortment of organic compounds, 24.3 Prenyltransferase and terpene the great majority of which do not appear to participate directly in synthase reactions growth and development. These substances, traditionally referred to 24.4 Modification of terpenoid as secondary metabolites, often are differentially distributed among skeletons limited taxonomic groups within the plant kingdom. Their functions, 24.5 Toward transgenic terpenoid many of which remain unknown, are being elucidated with increas- production ing frequency. The primary metabolites, in contrast, such as phyto- 24.6 Alkaloids sterols, acyl lipids, nucleotides, amino acids, and organic acids, are 24.7 Alkaloid biosynthesis found in all plants and perform metabolic roles that are essential 24.8 Biotechnological application and usually evident. of alkaloid biosynthesis Although noted for the complexity of their chemical structures research and biosynthetic pathways, natural products have been widely per- 24.9 Phenylpropanoid and ceived as biologically insignificant and have historically received lit- phenylpropanoid-acetate tle attention from most plant biologists. Organic chemists, however, pathway metabolites have long been interested in these novel phytochemicals and have 24.10 Phenylpropanoid and investigated their chemical properties extensively since the 1850s. phenylpropanoid-acetate Studies of natural products stimulated development of the separa- biosynthesis tion techniques, spectroscopic approaches to structure elucidation, and synthetic methodologies that now constitute the foundation of 24.11 Biosynthesis of lignans, lignins, contemporary organic chemistry.
    [Show full text]
  • Primary and Secondary Metabolites
    PRIMARY AND SECONDARY METABOLITES INRODUCTION Metabolism-Metabolism constituents all the chemical transformations occurring in the cells of living organisms and these transformations are essential for life of an organism. Metabolites-End product of metabolic processes and intermediates formed during metabolic processes is called metabolites. Types of Metabolites Primary Secondary metabolites metabolites Primary metabolites A primary metabolite is a kind of metabolite that is directly involved in normal growth, development, and reproduction. It usually performs a physiological function in the organism (i.e. an intrinsic function). A primary metabolite is typically present in many organisms or cells. It is also referred to as a central metabolite, which has an even more restricted meaning (present in any autonomously growing cell or organism). Some common examples of primary metabolites include: ethanol, lactic acid, and certain amino acids. In higher plants such compounds are often concentrated in seeds and vegetative storage organs and are needed for physiological development because of their role in basic cell metabolism. As a general rule, primary metabolites obtained from higher plants for commercial use are high volume-low value bulk chemicals. They are mainly used as industrial raw materials, foods, or food additives and include products such as vegetable oils, fatty acids (used for making soaps and detergents), and carbohydrates (for example, sucrose, starch, pectin, and cellulose). However, there are exceptions to this rule. For example, myoinositol and ß-carotene are expensive primary metabolites because their extraction, isolation, and purification are difficult. carbohydr -ates hormones proteins Examples Nucleic lipids acids A plant produces primary metabolites that are involved in growth and metabolism.
    [Show full text]
  • A Case Study of Pansteatitis Outbreak in South Africa
    Metabolomics (2019) 15:38 https://doi.org/10.1007/s11306-019-1490-9 ORIGINAL ARTICLE Lipidomics for wildlife disease etiology and biomarker discovery: a case study of pansteatitis outbreak in South Africa Jeremy P. Koelmel1 · Candice Z. Ulmer2 · Susan Fogelson3 · Christina M. Jones4 · Hannes Botha5,6 · Jacqueline T. Bangma7 · Theresa C. Guillette8 · Wilmien J. Luus‑Powell6 · Joseph R. Sara6 · Willem J. Smit6 · Korin Albert9 · Harmony A. Miller10 · Matthew P. Guillette11 · Berkley C. Olsen12 · Jason A. Cochran13 · Timothy J. Garrett1,14 · Richard A. Yost1,14 · John A. Bowden2,15 Received: 8 October 2018 / Accepted: 13 February 2019 / Published online: 5 March 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Introduction Lipidomics is an emerging field with great promise for biomarker and mechanistic studies due to lipids diverse biological roles. Clinical research applying lipidomics is drastically increasing, with research methods and tools developed for clinical applications equally promising for wildlife studies. Objectives Limited research to date has applied lipidomics, especially of the intact lipidome, to wildlife studies. Therefore, we examine the application of lipidomics for in situ studies on Mozambique tilapia (Oreochromis mossambicus) in Loskop Dam, South Africa. Wide-scale mortality events of aquatic life associated with an environmentally-derived inflammatory disease, pansteatitis, have occurred in this area. Methods The lipidome of adipose tissue (n = 31) and plasma (n = 51) from tilapia collected from Loskop Dam were char- acterized using state of the art liquid chromatography coupled to high-resolution tandem mass spectrometry. Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s1130 6-019-1490-9) contains supplementary material, which is available to authorized users.
    [Show full text]
  • Machine Learning Tools for Biomarker Discovery Chloé-Agathe Azencott
    Machine learning tools for biomarker discovery Chloé-Agathe Azencott To cite this version: Chloé-Agathe Azencott. Machine learning tools for biomarker discovery. Machine Learning [stat.ML]. Sorbonne Université UPMC, 2020. tel-02354924v2 HAL Id: tel-02354924 https://hal.archives-ouvertes.fr/tel-02354924v2 Submitted on 24 Jan 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. MACHINE LEARNING TOOLS FOR BIOMARKER DISCOVERY Chloé-Agathe Azencott Habilitation à Diriger des Recherches Déposée à l’UFR Ingénierie de Sorbonne Université Spécialité Informatique January 30, 2020 Membres du jury M. Mario Marchand (Université Laval, Canada) Rapporteur Mme Nataša Pržulj (University College London, UK, and Barcelona Supercomputing Center, Spain) Rapporteuse M. Bertrand Thirion (Inria Saclay, France) Rapporteur M. Michel Blum (Université Grenoble Alpes, France) Examinateur M. Grégory Nuel (Sorbonne Université, France) Examinateur Mme Marylyn Ritchie (University of Pennsylvania, USA) Examinatrice RÉSUMÉ Mes travaux de recherche s’inscrivent dans le cadre du développement de techniques d’apprentissage statistique (« machine learning ») pour la recherche thérapeutique. Ils visent en particulier à proposer des outils informatiques permettant d’exploiter des jeux de données pour en extraire des hypothèses biologiques expliquant au niveau génomique ou moléculaire les différences entre échantillons observées à un niveau macroscopique.
    [Show full text]
  • Applications of Metabolomics - a Systematic Study of the Unique Chemical Fingerprints: an Overview
    Volume 3, Issue 1, July – August 2010; Article 019 ISSN 0976 – 044X APPLICATIONS OF METABOLOMICS - A SYSTEMATIC STUDY OF THE UNIQUE CHEMICAL FINGERPRINTS: AN OVERVIEW Satyanand Tyagi1*, Raghvendra2, Usha Singh3, Taruna Kalra4, Kavita Munjal4 1 Department of Pharmaceutical Chemistry, K.N.G.D Modi Institute of Pharmaceutical Education & Research, Modinagar, Ghaziabad (dt), U.P, India-201204. 2 Department of Pharmaceutics, Aligarh College of Pharmacy, Aligarh (dt), U.P, India-202001. 3 Pharmacist, Max Neeman International Ltd, Okhla Phase - 3, New Delhi, India-110020. 4 Department of Pharmacy, B.S.Anangpuria Educational Institutes, Faridabad (dt), Haryana, India-121004. *Email: [email protected] ABSRTACT Metabolomics is a newborn cousin to genomics and proteomics. Specifically, metabolomics involves the rapid, high throughput characterization of the small molecule metabolites found in an organism. Since the metabolome is closely tied to the genotype of an organism, its physiology and its environment, metabolomics offers a unique opportunity to look at genotype-phenotype as well as genotype-envirotype relationships. Metabolomics is increasingly being used in a variety of health applications including pharmacology, pre-clinical drug trials, toxicology, transplant monitoring, newborn screening and clinical chemistry. However, a key limitation to metabolomics is the fact that the human metabolome is not at all well characterized. The growing field called Metabolomics detects and quantifies the low molecular weight molecules, known as metabolites (constituents of the metabolome), produced by active, living cells under different conditions and times in their life cycles. NMR is playing an important role in metabolomics because of its ability to observe mixtures of small molecules in living cells or in cell extracts.
    [Show full text]