Metabolomics

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‘Omics Family Tree

W. M. Claudino, et al., Journal of Clinical Oncology, 2007, 25(19), pp. 2840-28465/2/2014

Metabolomicsmɪˈtabəlɒmɪks/

Noun BIOCHEMISTRY

noun: metabolomics

1. The scientific study of the set of metabolites present within an organism, cell, or tissue.

The Oxford Dictionary

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How are metabolites influenced?

W. M. Claudino, et al., Journal of Clinical Oncology, 2007, 25(19), pp. 2840-28465/2/2014

Instrumental Analysis

• Gas Chromatography Mass Spectrometry (GC-MS)

• High Performance Liquid Chromatography (HPLC)

• Nanostructure Initiator Mass Spectrometry (NIMS)

• Secondary Ion Mass Spectrometry (SIMS)

• Nuclear Magnetic Resonance (NMR)5/2/2014

Image : www.metabolomics.biozentrum.uni-wuerzburg.de/research1/5/2/2014

Metabolic Fingerprinting

• Generally a no a priori approach

• Diagnostic based upon correlation of metabolites

• Qualitative analysis

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Metabolic Fingerprinting

H. Wang, et al., Molecular Cancer, 2013, 12(121). DOI: 10.1186/1476-4598-12-121

600 MHz representative 1H NMR spectra of tissue samples.

A normal controlB stage I of rectal cancerC stage II of rectal cancerD stage III of rectal cancerE stage IV of rectal cancer.

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Principal Component Analysis

Principal Component Analysis (PCA) scores plot showing discriminate metabolites from cancer tissues, versus normal controls

H. Wang, et al., Molecular Cancer, 2013, 12(121). DOI: 10.1186/1476-4598-12-121

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Orthogonal Projections to Latent Structures

What in X is related to Y – PredictiveWhat in X is not related to Y – Orthogonal(J. Trygg 2010)

H. Wang, et al., Molecular Cancer, 2013, 12(121). DOI: 10.1186/1476-4598-12-121

Image:

Positive region – Cancerous tissues

Negative region – Normal tissues

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Statistical Validation of Multivariate Models

H. Wang, et al., Molecular Cancer, 2013, 12(121). DOI: 10.1186/1476-4598-12-121

R2 = Explained Variance

Q2 = Predictable ability of the model

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Metabolite Screening and Targeted Analysis

• Requires some prior knowledge

• Identification of metabolites

• Quantitative approach

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1. Human Metabolome Database (www.hmdb.ca)

2. Pubchem (http://pubchem.ncbi.nlm.nih.gov)

3. Metabolights (www.ebi.ac.uk/metabolights)

4. Kegg (www.genome.jp/kegg)

5. Metlin (http://metlin.scripps.edu)

6. Massbank (www.massbank.jp)

Metabolite Screening and Targeted Analysis

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Mestrelab : Mnova

• Predicts NMR spectra of compounds

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http://www.hmdb.ca/metabolites/HMDB00190

Example

http://www.frontiersin.org/Journal/10.3389/fncel.2013.00179/full

Fetal Bovine Serum (FBS) - 1H NMR spectrum acquired on 300MHz Oxford Instrument – 04/02/2014

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Recommended Reading

1. D. I. Broadhurst and D. B. Kell, Metabolomics, 2007, 2(4), pp. 171-196. DOI: 10.1007-511306-006-0037-z

2. R. Goodacre, et al., Trends in Biotechnol., 2004, 22(5), pp. 245-252.

3. R. Zenobi, Science, 2013, 342, pp. 1201-1212. DOI: 10.1126/science.1243259

4. N. V. Reo, Drug Chem. Toxicol., 2002, 25(4), pp. 375-382.

5. W. M. Claudino, et al., Journal of Clinical Oncology, 2007, 25(19), pp. 2840-2846.

6. H. Wang, et al., Molecular Cancer, 2013, 12(121).

7. D. L. Massart et al., Chemometrics : A Textbook, Elsevier, New York, 1988.

8. J. Trygg and S. Wold, J. Chemom., 2002, 16(3), pp. 119-128.5/2/2014