A View from Above: Cloud Plots to Visualize Global Metabolomic Data

Patti, Gary J.; Tautenhahn, Ralf; Rinehart, Duane; Cho, Kevin; Shriver, Leah P.; Manchester, Marianne; Nikolskiy, Igor; Johnson, Caroline H.; Mahieu, Nathaniel G.; Siuzdak, Gary

doi:10.1021/ac3029745

A View from Above: Cloud Plots to Visualize Global Metabolomic Data

Journal Article · Mon Dec 03 00:00:00 EST 2012 · Analytical Chemistry

DOI:https://doi.org/10.1021/ac3029745· OSTI ID:1788445

Patti, Gary J. ^[1]; Tautenhahn, Ralf ^[2]; Rinehart, Duane ^[2]; Cho, Kevin ^[1]; Shriver, Leah P. ^[3]; Manchester, Marianne ^[4]; Nikolskiy, Igor ^[1]; Johnson, Caroline H. ^[2]; Mahieu, Nathaniel G. ^[1]; Siuzdak, Gary ^[2]

Washington Univ., St. Louis, MO (United States). Departments of Chemistry, Genetics, and Medicine
The Scripps Research Inst., La Jolla, CA (United States). Departments of Chemistry, Molecular Biology, and Center for Metabolomics
Univ. of Akron, OH (United States). Departments of Chemistry and Biology; Univ. of California, San Diego, CA (United States). Skaggs School of Pharmacy and Pharmaceutical Sciences
Univ. of California, San Diego, CA (United States). Skaggs School of Pharmacy and Pharmaceutical Sciences

Global metabolomics describes the comprehensive analysis of small molecules in a biological system without bias. With mass spectrometry-based methods, global metabolomic data sets typically comprise thousands of peaks, each of which is associated with a mass-to-charge ratio, retention time, fold change, p-value, and relative intensity. Although several visualization schemes have been used for metabolomic data, most commonly used representations exclude important data dimensions and therefore limit interpretation of global data sets. Given that metabolite identification through tandem mass spectrometry data acquisition is a time-limiting step of the untargeted metabolomic workflow, simultaneous visualization of these parameters from large sets of data could facilitate compound identification and data interpretation. Here, we present such a visualization scheme of global metabolomic data using a so-called “cloud plot” to represent multidimensional data from septic mice. While much attention has been dedicated to lipid compounds as potential biomarkers for sepsis, the cloud plot shows that alterations in hydrophilic metabolites may provide an early signature of the disease prior to the onset of clinical symptoms. The cloud plot is an effective representation of global mass spectrometry-based metabolomic data, and we describe how to extract it as standard output from our XCMS metabolomic software.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1788445

Journal Information:: Analytical Chemistry, Journal Name: Analytical Chemistry Journal Issue: 2 Vol. 85; ISSN 0003-2700

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

References (28)

Suitability of silica hydride stationary phase, aqueous normal phase chromatography for untargeted metabolomic profiling of Enterococcus faecium and Staphylococcus aureus Weisenberg, Scott A.; Butterfield, Tiffany R.; Fischer, Steven M. Journal of Separation Science, Vol. 32, Issue 13 https://doi.org/10.1002/jssc.200900256	journal	June 2009
Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: Involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB Sun, Qi; Chen, Ling; Gao, Mengyu International Immunopharmacology, Vol. 12, Issue 1 https://doi.org/10.1016/j.intimp.2011.10.018	journal	January 2012
The inflammatory response in sepsis Bosmann, Markus; Ward, Peter A. Trends in Immunology, Vol. 34, Issue 3 https://doi.org/10.1016/j.it.2012.09.004	journal	March 2013
Opening up the "Black Box": Metabolic phenotyping and metabolome-wide association studies in epidemiology Bictash, Magda; Ebbels, Timothy M.; Chan, Queenie Journal of Clinical Epidemiology, Vol. 63, Issue 9 https://doi.org/10.1016/j.jclinepi.2009.10.001	journal	September 2010
XCMS: Processing Mass Spectrometry Data for Metabolite Profiling Using Nonlinear Peak Alignment, Matching, and Identification Smith, Colin A.; Want, Elizabeth J.; O'Maille, Grace Analytical Chemistry, Vol. 78, Issue 3 https://doi.org/10.1021/ac051437y	journal	February 2006
Expanding Coverage of the Metabolome for Global Metabolite Profiling Yanes, Oscar; Tautenhahn, Ralf; Patti, Gary J. Analytical Chemistry, Vol. 83, Issue 6 https://doi.org/10.1021/ac102981k	journal	March 2011
XCMS Online: A Web-Based Platform to Process Untargeted Metabolomic Data Tautenhahn, Ralf; Patti, Gary J.; Rinehart, Duane Analytical Chemistry, Vol. 84, Issue 11 https://doi.org/10.1021/ac300698c	journal	June 2012
Bayesian Independent Component Analysis Recovers Pathway Signatures from Blood Metabolomics Data Krumsiek, Jan; Suhre, Karsten; Illig, Thomas Journal of Proteome Research, Vol. 11, Issue 8 https://doi.org/10.1021/pr300231n	journal	June 2012
Model‐driven multi‐omic data analysis elucidates metabolic immunomodulators of macrophage activation Bordbar, Aarash; Mo, Monica L.; Nakayasu, Ernesto S. Molecular Systems Biology, Vol. 8, Issue 1 https://doi.org/10.1038/msb.2012.21	journal	January 2012
Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression Sreekumar, Arun; Poisson, Laila M.; Rajendiran, Thekkelnaycke M. Nature, Vol. 457, Issue 7231 https://doi.org/10.1038/nature07762	journal	February 2009
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease Wang, Zeneng; Klipfell, Elizabeth; Bennett, Brian J. Nature, Vol. 472, Issue 7341 https://doi.org/10.1038/nature09922	journal	April 2011
An accelerated workflow for untargeted metabolomics using the METLIN database Tautenhahn, Ralf; Cho, Kevin; Uritboonthai, Winnie Nature Biotechnology, Vol. 30, Issue 9 https://doi.org/10.1038/nbt.2348	journal	September 2012
Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin Patti, Gary J.; Yanes, Oscar; Shriver, Leah P. Nature Chemical Biology, Vol. 8, Issue 3 https://doi.org/10.1038/nchembio.767	journal	January 2012
PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide Göggel, Rolf; Winoto-Morbach, Supandi; Vielhaber, Gabriele Nature Medicine, Vol. 10, Issue 2 https://doi.org/10.1038/nm977	journal	January 2004
Metabolomics: from small molecules to big ideas Baker, Monya Nature Methods, Vol. 8, Issue 2 https://doi.org/10.1038/nmeth0211-117	journal	January 2011
Metabolomics: the apogee of the omics trilogy Patti, Gary J.; Yanes, Oscar; Siuzdak, Gary Nature Reviews Molecular Cell Biology, Vol. 13, Issue 4 https://doi.org/10.1038/nrm3314	journal	March 2012
Torbafylline (HWA 448) inhibits enhanced skeletal muscle ubiquitin–proteasome-dependent proteolysis in cancer and septic rats Combaret, Lydie; Tilignac, Thomas; Claustre, Agnès Biochemical Journal, Vol. 361, Issue 2 https://doi.org/10.1042/bj3610185	journal	January 2002
Activated platelets mediate inflammatory signaling by regulated interleukin 1β synthesis Lindemann, Stephan; Tolley, Neal D.; Dixon, Dan A. Journal of Cell Biology, Vol. 154, Issue 3 https://doi.org/10.1083/jcb.200105058	journal	August 2001
Passive immunization of mice against D factor blocks lethality and cytokine release during endotoxemia. Block, M. I.; Berg, M.; McNamara, M. J. Journal of Experimental Medicine, Vol. 178, Issue 3 https://doi.org/10.1084/jem.178.3.1085	journal	September 1993
Lipopolysaccharide and sepsis-associated myocardial dysfunction Balija, Tara M.; Lowry, Stephen F. Current Opinion in Infectious Diseases, Vol. 24, Issue 3 https://doi.org/10.1097/QCO.0b013e32834536ce	journal	January 2011
The Cinderella story of metabolic profiling: does metabolomics get to go to the functional genomics ball? Griffin, Julian L. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 361, Issue 1465 https://doi.org/10.1098/rstb.2005.1734	journal	November 2005
Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates Yost, Christian C.; Cody, Mark J.; Harris, Estelle S. Blood, Vol. 113, Issue 25 https://doi.org/10.1182/blood-2008-07-171629	journal	June 2009
Gram-Negative Infection Increases Noninsulin-Mediated Glucose Disposal* Lang, Charles H.; Dobrescu, Cornel Endocrinology, Vol. 128, Issue 2 https://doi.org/10.1210/endo-128-2-645	journal	February 1991
Metabolomic Profiling in LRRK2-Related Parkinson's Disease Johansen, Krisztina K.; Wang, Lei; Aasly, Jan O. PLoS ONE, Vol. 4, Issue 10 https://doi.org/10.1371/journal.pone.0007551	journal	October 2009
Autophagy and Skeletal Muscles in Sepsis Mofarrahi, Mahroo; Sigala, Ioanna; Guo, Yeting PLoS ONE, Vol. 7, Issue 10 https://doi.org/10.1371/journal.pone.0047265	journal	October 2012
Adrenal Insufficiency in Sepsis Annane, Djillali Current Pharmaceutical Design, Vol. 14, Issue 19 https://doi.org/10.2174/138161208784980626	journal	July 2008
Spectrum of sepsis mediators source control and management of bundles Gullo, Antonino Frontiers in Bioscience, Vol. E2, Issue 3 https://doi.org/10.2741/e150	journal	January 2010
Serum Protein-Bound Carbohydrates and Lipids in Cholera Banerjee, S.; Bhaduri, J. N. Experimental Biology and Medicine, Vol. 101, Issue 2 https://doi.org/10.3181/00379727-101-24931	journal	June 1959

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Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity Breit, Marc; Netzer, Michael; Weinberger, Klaus M. PLOS Computational Biology, Vol. 11, Issue 8 https://doi.org/10.1371/journal.pcbi.1004454	journal	August 2015
The Lipopolysaccharide-Induced Metabolome Signature in Arabidopsis thaliana Reveals Dynamic Reprogramming of Phytoalexin and Phytoanticipin Pathways Finnegan, Tarryn; Steenkamp, Paul A.; Piater, Lizelle A. PLOS ONE, Vol. 11, Issue 9 https://doi.org/10.1371/journal.pone.0163572	journal	September 2016
The proteomic and metabolomic characterization of exercise-induced sweat for human performance monitoring: A pilot investigation Harshman, Sean W.; Pitsch, Rhonda L.; Smith, Zachary K. PLOS ONE, Vol. 13, Issue 11 https://doi.org/10.1371/journal.pone.0203133	journal	November 2018
An improved method for extraction of polar and charged metabolites from cyanobacteria Prasannan, Charulata B.; Jaiswal, Damini; Davis, Rose PLOS ONE, Vol. 13, Issue 10 https://doi.org/10.1371/journal.pone.0204273	journal	October 2018
A Novel Role for Triglyceride Metabolism in Foxp3 Expression Howie, Duncan; Ten Bokum, Annemieke; Cobbold, Stephen Paul Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.01860	journal	August 2019
Using “Omics” and Integrated Multi-Omics Approaches to Guide Probiotic Selection to Mitigate Chytridiomycosis and Other Emerging Infectious Diseases Rebollar, Eria A.; Antwis, Rachael E.; Becker, Matthew H. Frontiers in Microbiology, Vol. 7 https://doi.org/10.3389/fmicb.2016.00068	journal	February 2016
Intriguing Interaction of Bacteriophage-Host Association: An Understanding in the Era of Omics Parmar, Krupa M.; Gaikwad, Saurabh L.; Dhakephalkar, Prashant K. Frontiers in Microbiology, Vol. 8 https://doi.org/10.3389/fmicb.2017.00559	journal	April 2017
Profiling of Altered Metabolomic States in Nicotiana tabacum Cells Induced by Priming Agents Mhlongo, Msizi I.; Steenkamp, Paul A.; Piater, Lizelle A. Frontiers in Plant Science, Vol. 7 https://doi.org/10.3389/fpls.2016.01527	journal	October 2016
Metabolomic analysis of human oral cancer cells with adenylate kinase 2 or phosphorylate glycerol kinase 1 inhibition Ji, Eoon Hye; Cui, Li; Yuan, Xiaoqing Journal of Cancer, Vol. 8, Issue 2 https://doi.org/10.7150/jca.17521	journal	January 2017
Metabolomics in Stem Cell Biology Research Sun, Zhen; Zhao, Jing; Yu, Hua Computational Stem Cell Biology https://doi.org/10.1007/978-1-4939-9224-9_15	book	January 2019
Metabolome changes are induced in the arbuscular mycorrhizal fungus Gigaspora margarita by germination and by its bacterial endosymbiont Dearth, Stephen P.; Castro, Hector F.; Venice, Francesco Mycorrhiza, Vol. 28, Issue 5-6 https://doi.org/10.1007/s00572-018-0838-8	journal	June 2018
Screening of Microbial Volatile Organic Compounds for Detection of Disease in Cattle: Development of Lab-scale Method Maurer, Devin L.; Ellis, Christine K.; Thacker, Tyler C. Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-47907-w	journal	August 2019
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Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition Ballinger, Elaine; Mosior, John; Hartman, Travis Science, Vol. 363, Issue 6426 https://doi.org/10.1126/science.aau8959	journal	January 2019
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