Chapter 1 Introduction

Information in living organism commuicates along the Genomics, Transcriptomics, Proteomics and Metabolomics in Central dogma. Following such stream, we might answer certain problems in different scales from individual, population, community to ecosystem. Metabolomics (i.e., the profiling and quantitation of metabolites in body fluids) is a relatively new field of “omics” studies. Different from other omics studies, metabolomics always focused on small moleculars with much lower mass than polypeptide with single or doubled charged ions. Metabolomics studies are always performed in GC-MS, GC*GC-MS(Tian et al. 2016), LC-MS, LC-MS/MS or NMR. This workflow would only cover mass spectrometry based metabolomics or XC-MS based research.

1.1 History

1.1.1 History of Mass Spectrometry

  • 1913, Sir Joseph John Thomson “Rays of Positive Electricity and Their Application to Chemical Analyses.”
Sir Joseph John Thomson "Rays of Positive Electricity and Their Application to Chemical Analyses."

Figure 1.1: Sir Joseph John Thomson “Rays of Positive Electricity and Their Application to Chemical Analyses.”

  • Petroleum industry bring mass spectrometry from physics to chemistry

  • The first commercial mass spectrometer is from Consolidated Engineering Corp to analysis simple gas mixtures from petroleum

  • In World War II, U.S. use mass spectrometer to separate and enrich isotopes of uranium in Manhattan Project

  • U.S. also use mass spectrometer for organic compounds during wartime and extend the application of mass spectrometer

  • 1946, TOF, William E. Stephens

  • 1970s, quadrupole mass analyzer

  • 1970s, R. Graham Cooks developed mass-analyzed ion kinetic energy spectrometry, or MIKES to make MRM analysis for multi-stage mass sepctrometry

  • 1980s, MALDI rescue TOF and mass spectrometry move into biological application

  • 1990s, Orbitrap mass spectrometry

  • 2010s, Aperture Coding mass spectrometry

1.1.2 History of Metabolomcis

According to this book section(Kusonmano, Vongsangnak, and Chumnanpuen 2016):

Metabolomics timeline during pre- and post-metabolomics era

Figure 1.2: Metabolomics timeline during pre- and post-metabolomics era

  • 2000-1500 BC some traditional Chinese doctors who began to evaluate the glucose level in urine of diabetic patients using ants

  • 300 BC ancient Egypt and Greece that traditionally determine the urine taste to diagnose human diseases

  • 1913 Joseph John Thomson and Francis William Aston mass spectrometry

  • 1946 Felix Bloch and Edward Purcell Nuclear magnetic resonance

  • late 1960s chromatographic separation technique

  • 1971 Pauling’s research team “Quantitative Analysis of Urine Vapor and Breath by Gas–Liquid Partition Chromatography”

  • Willmitzer and his research team pioneer group in metabolomics which suggested the promotion of the metabolomics field and its potential applications from agriculture to medicine and other related areas in the biological sciences

  • 2007 Human Metabolome Project consists of databases of approximately 2500 metabolites, 1200 drugs, and 3500 food components

  • post-metabolomics era high-throughput analytical techniques

1.2 Reviews and tutorials

Some new reviews and tutorials related to this workflow could be found in those papers(Alonso, Marsal, and Julià 2015; Cajka and Fiehn 2016; Lu and Xu 2008; Schrimpe-Rutledge et al. 2016; Townsend et al. 2016; Barnes et al. 2016b; Barnes et al. 2016a).

Also I noticed more and more papers showed a bunch of data process methods as strategy for metabolomics(Watrous et al. 2017; Robbat Jr. et al. 2017). If you only need metabolomics as tools to tell your story, such stratrgy could be a quick start for you.

For software, check this review(Misra and family=Hooft 2016).

Here is the slides for metabolomics data analysis workshop and I have made presentations twice in UWaterloo and UC Irvine. Such slides would be updated silent.

1.4 Workflow


Tian, Tze-Feng, San-Yuan Wang, Tien-Chueh Kuo, Cheng-En Tan, Guan-Yuan Chen, Ching-Hua Kuo, Chi-Hsin Sally Chen, Chang-Chuan Chan, Olivia A. Lin, and Y. Jane Tseng. 2016. “Web Server for Peak Detection, Baseline Correction, and Alignment in Two-Dimensional Gas Chromatography Mass Spectrometry-Based Metabolomics Data.” Anal. Chem. 88 (21): 10395–10403. doi:10.1021/acs.analchem.6b00755.

Kusonmano, Kanthida, Wanwipa Vongsangnak, and Pramote Chumnanpuen. 2016. “Informatics for Metabolomics.” In Translational Biomedical Informatics, 91–115. Advances in Experimental Medicine and Biology. Springer, Singapore. doi:10.1007/978-981-10-1503-8_5.

Alonso, Arnald, Sara Marsal, and Antonio Julià. 2015. “Analytical Methods in Untargeted Metabolomics: State of the Art in 2015.” Front Bioeng Biotechnol 3 (March). doi:10.3389/fbioe.2015.00023.

Cajka, Tomas, and Oliver Fiehn. 2016. “Toward Merging Untargeted and Targeted Methods in Mass Spectrometry-Based Metabolomics and Lipidomics.” Anal. Chem. 88 (1): 524–45. doi:10.1021/acs.analchem.5b04491.

Lu, Xin, and Guowang Xu. 2008. “LC-MS Metabonomics Methodology in Biomarker Discovery.” In Biomarker Methods in Drug Discovery and Development, edited by Feng Wang, 291–315. Methods in Pharmacology and Toxicology. Humana Press. doi:10.1007/978-1-59745-463-6_14.

Schrimpe-Rutledge, Alexandra C., Simona G. Codreanu, Stacy D. Sherrod, and John A. McLean. 2016. “Untargeted Metabolomics StrategiesChallenges and Emerging Directions.” J. Am. Soc. Mass Spectrom. 27 (12): 1897–1905. doi:10.1007/s13361-016-1469-y.

Townsend, Mary K., Hugues Aschard, Immaculata De Vivo, Karin B. Michels, and Peter Kraft. 2016. “Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses’ Health Studies.” Am J Public Health 106 (9): 1663–8. doi:10.2105/AJPH.2016.303344.

Barnes, Stephen, H. 2016b. “Training in Metabolomics Research. II. Processing and Statistical Analysis of Metabolomics Data, Metabolite Identification, Pathway Analysis, Applications of Metabolomics and Its Future.” J. Mass Spectrom. 51 (8): 535–48. doi:10.1002/jms.3780.

Barnes, Stephen, H. Paul Benton, Krista Casazza, Sara J. Cooper, Xiangqin Cui, Xiuxia Du, Jeffrey Engler, et al. 2016a. “Training in Metabolomics Research. I. Designing the Experiment, Collecting and Extracting Samples and Generating Metabolomics Data.” J. Mass Spectrom. 51 (7): 461–75. doi:10.1002/jms.3782.

Watrous, Jeramie D., Mir Henglin, Brian Claggett, Kim A. Lehmann, Martin G. Larson, Susan Cheng, and Mohit Jain. 2017. “Visualization, Quantification, and Alignment of Spectral Drift in Population Scale Untargeted Metabolomics Data.” Anal. Chem. 89 (3): 1399–1404. doi:10.1021/acs.analchem.6b04337.

Robbat Jr., Albert, Nicole Kfoury, Eugene Baydakov, and Yuriy Gankin. 2017. “Optimizing Targeted/Untargeted Metabolomics by Automating Gas Chromatography/Mass Spectrometry Workflows.” Journal of Chromatography A 1505 (July): 96–105. doi:10.1016/j.chroma.2017.05.017.

Misra, Biswapriya B., and prefix=van der family=Hooft given=Justin J. J. 2016. “Updates in Metabolomics Tools and Resources: 20142015.” ELECTROPHORESIS 37 (1): 86–110. doi:10.1002/elps.201500417.

Kapoore, Rahul Vijay, and Seetharaman Vaidyanathan. 2016. “Towards Quantitative Mass Spectrometry-Based Metabolomics in Microbial and Mammalian Systems.” Phil. Trans. R. Soc. A 374 (2079): 20150363. doi:10.1098/rsta.2015.0363.

Jorge, Tiago F., Ana T. Mata, and Carla António. 2016. “Mass Spectrometry as a Quantitative Tool in Plant Metabolomics.” Phil. Trans. R. Soc. A 374 (2079): 20150370. doi:10.1098/rsta.2015.0370.

Zampieri, Mattia, Karthik Sekar, Nicola Zamboni, and Uwe Sauer. 2017. “Frontiers of High-Throughput Metabolomics.” Current Opinion in Chemical Biology, Omics, 36 (February): 15–23. doi:10.1016/j.cbpa.2016.12.006.