Analysis at the Metabolomic Scale
Dmitry Grapov, PhD
Tools for Metabolomic Data Analysis and Visualization
1. Visualization (how does it look?)
• histograms, density plots, box plots, line plots, scatter plots, networks, etc.
2. Statistical Analysis (what is statistically significant?)
• summary tables, ANOVA, FDR adjustment, power analysis, etc.
3. Exploration (what are the major patterns/trends?)
• clustering, PCA, ICA, etc.
4. Predictive Modeling (what explains my hypothesis?)
• mixed effects, partial least squares (O-/PLS/-DA), etc.
5. Network Analysis (how are things related?)
• Pathway Enrichment
• Biochemical, mass spectral, empirical, etc.
6. Network Mapping
Common Data Analysis Tasks
Featured Tools
Data Analysis and Visualization• DeviumWeb- Dynamic multivariate data analysis and visualization
platformurl: https://github.com/dgrapov/DeviumWeb
• imDEV- Microsoft Excel add-in for multivariate analysisurl: http://sourceforge.net/projects/imdev/
Network Analysis• MetaMapR- Network analysis tools for metabolomics
url: https://github.com/dgrapov/MetaMapR
Network Mapping• MetaMapR + DeviumWeb + Cytoscape
DeviumWebhttps://github.com/dgrapov/DeviumWeb
Network Mapping
Visualization and analysis of statistical and multivariate results within a biochemical and/or empirical context.
Conduct Data Analysis
Generate Network
Map Results to Network
Grapov D., Fiehn O., Multivariate and network tools for analysis and visualization of metabolomic data, ASMS, June 08, 2013, Minneapolis, MN
Network Generation
Biochemical • enzymatic transformations
Structural Similarity• structural fingerprints • mass spectra
Empirical (dependency)• correlation• partial-correlation
BMC Bioinformatics 2012, 13:99 doi:10.1186/1471-2105-13-99
Metabolic Perturbations in Tumorigenesis
Biochemical and chemical similarity network comparing changes in metabolites between tumor and control tissue
Mappings:• direction of change • statistical significance • multivariate importance• molecular biochemical
domain
Biochemical Relationships
http://www.genome.jp/dbget-bin/www_bget?rn:R00975
Structural Similarity
http://pubchem.ncbi.nlm.nih.gov//score_matrix/score_matrix.cgi
Empirical NetworksExperiment specific data driven relationships can offer novel insight into biochemical perturbations urea cycle
nucleotide
synthesis
protein
glycosylation
Mass Spectral NetworksUse mass spectra as a proxy for structure to help make sense of unknown compounds’ biochemical identities.
Mix and match different relationships to help narrow down structures of unknowns
Partial derivatization products of glucose
MetaMapRhttps://github.com/dgrapov/MetaMapR
Data visualization as form of data analysis
DM
Liver CYP2D6
Dextromethorphan = additives in
dextrorphan
• high fructose corn syrup
• antioxidants
• flavor
Identification of treatment effects
Differential metabolic responses
Treatment 1 Treatment 2
Other Resources
• TeachingDemos- Tutorials and Demonstrations in R• url: http://sourceforge.net/projects/teachingdemos/?source=directory• url: https://github.com/dgrapov/TeachingDemos
• CDS Blog- Data analysis Case Studies and Tutorialsurl: http://imdevsoftware.wordpress.com/
[email protected] metabolomics.ucdavis.edu
This research was supported in part by NIH 1 U24 DK097154