From Samples to Insights into Metabolism: Uncovering Biologically Relevant Information in LC-HRMS Metabolomics Data

Metabolites
Julijana Ivanisevic, Elizabeth J Want

Abstract

Untargeted metabolomics (including lipidomics) is a holistic approach to biomarker discovery and mechanistic insights into disease onset and progression, and response to intervention. Each step of the analytical and statistical pipeline is crucial for the generation of high-quality, robust data. Metabolite identification remains the bottleneck in these studies; therefore, confidence in the data produced is paramount in order to maximize the biological output. Here, we outline the key steps of the metabolomics workflow and provide details on important parameters and considerations. Studies should be designed carefully to ensure appropriate statistical power and adequate controls. Subsequent sample handling and preparation should avoid the introduction of bias, which can significantly affect downstream data interpretation. It is not possible to cover the entire metabolome with a single platform; therefore, the analytical platform should reflect the biological sample under investigation and the question(s) under consideration. The large, complex datasets produced need to be pre-processed in order to extract meaningful information. Finally, the most time-consuming steps are metabolite identification, as well as metabolic pathway an...Continue Reading

References

Dec 25, 2003·Bioinformatics·Jelle J GoemanHans C van Houwelingen
Jul 1, 2006·Analytical Chemistry·Orla TeahanHector C Keun
Feb 3, 2007·Journal of Proteome Research·Elizabeth J WantGary Siuzdak
Oct 28, 2008·Nucleic Acids Research·David S WishartIan Forsythe
Dec 2, 2008·BMC Bioinformatics·Ralf TautenhahnSteffen Neumann
Aug 26, 2009·Analytical Chemistry·Roman MylonasFrederique Lisacek
May 7, 2010·Nucleic Acids Research·Ludovic CottretFabien Jourdan
May 8, 2010·Nature Protocols·Elizabeth J WantJeremy K Nicholson
Jul 14, 2010·Journal of Mass Spectrometry : JMS·Hisayuki HoraiTakaaki Nishioka
Feb 19, 2011·Analytical Chemistry·Oscar YanesGary Siuzdak
Mar 19, 2011·Bioinformatics·Arnald AlonsoSara Marsal
May 7, 2011·Nucleic Acids Research·Takuji YamadaPeer Bork
Oct 6, 2011·Journal of Separation Science·Gary J Patti
Feb 22, 2012·Nature Protocols·Gary J PattiGary Siuzdak
Mar 23, 2012·Nature Reviews. Molecular Cell Biology·Gary J PattiGary Siuzdak
Apr 27, 2012·Analytical Chemistry·Ralf TautenhahnGary Siuzdak
Sep 12, 2012·Nature Biotechnology·Ralf TautenhahnGary Siuzdak
Oct 13, 2012·Metabolomics : Official Journal of the Metabolomic Society·Christoph SteinbeckJulian L Griffin
Dec 12, 2012·Nature Protocols·Elizabeth J WantJeremy K Nicholson
Feb 26, 2013·Electrophoresis·Zacarías LeónAgustín Lahoz
Jul 19, 2013·PLoS Computational Biology·Shuzhao LiBali Pulendran
Jan 1, 2006·Metabolomics : Official Journal of the Metabolomic Society·Carina M RubinghAge K Smilde
Jun 10, 2014·Nature Biotechnology·Duane RinehartGary Siuzdak
Jun 27, 2014·American Journal of Epidemiology·Ioanna TzoulakiJohn P A Ioannidis
Oct 14, 2014·Trends in Analytical Chemistry : TRAC·Tomas Cajka, Oliver Fiehn
Dec 17, 2014·Analytical Chemistry·H Paul BentonGary Siuzdak
Feb 24, 2015·PLoS Computational Biology·Martina KutmonChris T Evelo
May 6, 2015·Nature Methods·Hiroshi TsugawaMasanori Arita
May 23, 2015·Nature Protocols·Jarrett D EgertsonMichael J MacCoss
May 23, 2015·Molecular Cell·Nicola ZamboniGary J Patti
Jan 1, 2013·Current Metabolomics·Bradley Worley, Robert Powers
Sep 8, 2015·Archives of Biochemistry and Biophysics·Ning LiYulan Wang
Oct 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ricardo R da SilvaRobert A Quinn
Feb 3, 2016·Journal of Cheminformatics·Christoph RuttkiesSteffen Neumann
Feb 19, 2016·Metabolites·Arthur S EdisonMark R Viant
Mar 17, 2016·Nature Reviews. Molecular Cell Biology·Caroline H JohnsonGary Siuzdak
Apr 27, 2016·Analytical Chemistry·Benjamin J BlaiseTimothy M D Ebbels
May 21, 2016·PLoS Computational Biology·Anwesha BohlerChris T Evelo
Jul 3, 2016·Analytical and Bioanalytical Chemistry·Stefanie Wernisch, Subramaniam Pennathur
Jul 18, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Olga DedaHelen G Gika
Oct 4, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Małgorzata PatejkoMichał J Markuszewski
Nov 20, 2016·Proceedings of the National Academy of Sciences of the United States of America·Justin J J van der HooftSimon Rogers
Dec 2, 2016·Nucleic Acids Research·Minoru KanehisaKanae Morishima
Dec 21, 2016·Bioinformatics·Alberto NoronhaRonan M T Fleming
Dec 28, 2016·Current Opinion in Chemical Biology·Laura K ReedArthur S Edison
Jan 16, 2017·Current Opinion in Chemical Biology·L Safak Yilmaz, Albertha Jm Walhout
Jan 31, 2017·Advances in Experimental Medicine and Biology·Andrew J ChetwyndGiovanny Rodriguez-Blanco
Mar 8, 2017·Journal of the American Society for Mass Spectrometry·Jeremy P KoelmelTimothy J Garrett
Mar 17, 2017·Nature Protocols·Giuseppe Paglia, Giuseppe Astarita
Apr 28, 2017·Nature Methods·Tao HuanGary Siuzdak
May 26, 2017·Electrophoresis·Vinicius Veri HernandesDanuta Dudzik
Jun 21, 2017·Critical Reviews in Analytical Chemistry·Zhi-Gang GongYong-Jiang Xu
Jun 28, 2017·Annual Review of Biochemistry·Wenyun LuJoshua D Rabinowitz
Jul 3, 2017·Cellular and Molecular Life Sciences : CMLS·Sarah HaytonRobert D Trengove
Aug 22, 2017·Journal of Pharmaceutical and Biomedical Analysis·Danuta DudzikCoral Barbas
Oct 19, 2017·Analytical Chemistry·Xavier Domingo-AlmenaraGary Siuzdak
Nov 15, 2017·Nucleic Acids Research·Denise N SlenterEgon Willighagen
Nov 16, 2017·Nucleic Acids Research·David S WishartAugustin Scalbert
Dec 8, 2017·The Analyst·Nicolas DrouinJulie Schappler
Dec 21, 2017·Journal of Bioscience and Bioengineering·Shin NishiumiMasaru Yoshida
Jan 30, 2018·PLoS Computational Biology·Antonio FabregatHenning Hermjakob
Jan 31, 2018·Analytical Chemistry·Carlos GuijasGary Siuzdak
Mar 6, 2018·Metabolomics : Official Journal of the Metabolomic Society·Antonio RosatoEdoardo Saccenti
Apr 6, 2018·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Shanchita R KhanRachel E Neale
May 3, 2018·Nucleic Acids Research·Ludovic CottretFabien Jourdan
May 16, 2018·Methods in Molecular Biology·Marina C M MartinsLuis Guilherme Furlan de Abreu
May 16, 2018·Nucleic Acids Research·Jasmine ChongJianguo Xia
Jul 20, 2018·Nature·Evanna L MillsEdward T Chouchani
Oct 12, 2018·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Hulda S JonasdottirMartin Giera
Nov 24, 2018·Journal of Pharmaceutical and Biomedical Analysis·Julia JacynaMichał J Markuszewski
Dec 7, 2018·Metabolites·Charmion Cruickshank-QuinnNichole Reisdorph
Dec 28, 2018·Journal of Pharmaceutical and Biomedical Analysis·Michał KazaPiotr J Rudzki
Jan 5, 2019·Analytical Chemistry·Ivana BlaženovićOliver Fiehn
Jan 27, 2019·Analytical Chemistry·Xavier Domingo-AlmenaraGary Siuzdak
Mar 5, 2019·Metabolomics : Official Journal of the Metabolomic Society·Kieu Trinh DoJan Krumsiek
Mar 5, 2019·Metabolomics : Official Journal of the Metabolomic Society·Michael R La FranoJohn W Newman
Mar 5, 2019·Metabolomics : Official Journal of the Metabolomic Society·Richard D BegerKrista A Zanetti
Mar 31, 2019·Analytica Chimica Acta·Jianing WangXianlin Han
Apr 5, 2019·Nature Communications·Xiaotao ShenZheng-Jiang Zhu
May 30, 2019·GigaScience·Martijn R MolenaarJ Bernd Helms
Jul 7, 2019·BMC Bioinformatics·Christoph RuttkiesStefan Posch
Jul 11, 2019·Proteomics·Changfeng HuXianlin Han
Sep 25, 2019·Metabolites·Jan StanstrupSteffen Neumann
Oct 6, 2019·Nucleic Acids Research·Ron CaspiPeter D Karp
Oct 12, 2019·Nucleic Acids Research·David S WishartMiguel Ramirez-Gaona
Nov 23, 2019·Current Protocols in Bioinformatics·Jasmine ChongJianguo Xia

Citations

May 13, 2020·Journal of Refractive Surgery·Min LiJun Zou
Jun 18, 2020·Metabolites·Ulf W LiebalLars M Blank
Oct 22, 2020·Metabolites·Gabriel RiquelmeMaría Eugenia Monge
Nov 25, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hector Gallart-AyalaJulijana Ivanisevic
Feb 20, 2021·The Analyst·Eulalia OlestiSerge Rudaz
Mar 30, 2021·Early Intervention in Psychiatry·Shusuke UekusaTakeshi Fukushima

Methods Mentioned

BETA
gastric bypass
serum collection
Nuclear Magnetic Resonance
Reversed-Phase Liquid Chromatography
PCA
NMR

Related Concepts

Biological Markers
Metabolism
Signal Pathways
Consideration
Metabolite
Metabolomics
Study

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells. It also follows CRISPR-Cas9 approaches to generating genetic mutants as a means of understanding the effect of genetics on phenotype.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Pediculosis pubis

Pediculosis pubis is a disease caused by a parasitic insect known as Pthirus pubis, which infests human pubic hair, as well as other areas with hair including eye lashes. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Rh Isoimmunization

Rh isoimmunization is a potentially preventable condition that occasionally is associated with significant perinatal morbidity or mortality. Discover the latest research on Rh Isoimmunization here.

Pharmacology of Proteinopathies

This feed focuses on the pharmacology of proteinopathies - diseases in which proteins abnormally aggregate (i.e. Alzheimer’s, Parkinson’s, etc.). Discover the latest research in this field with this feed.

Enzyme Evolution

This feed focuses on molecular models of enzyme evolution and new approaches (such as adaptive laboratory evolution) to metabolic engineering of microorganisms. Here is the latest research.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Related Papers

Methods in Molecular Biology
Samantha Riccadonna, Pietro Franceschi
Scandinavian Journal of Clinical and Laboratory Investigation
Leslie R EucedaTone F Bathen
Journal of Pharmaceutical and Biomedical Analysis
Yoric GagnebinRudaz Serge
Journal of Chromatography. a
Mikko Katajamaa, Matej Oresic
© 2021 Meta ULC. All rights reserved