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

Julijana Ivanisevic, Elizabeth J Want


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


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


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

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