metabolomic analysis during glucose infusion
DESCRIPTION
Metabolomics (GC/TOF, mass spectrometry) and informatics (PCA, PLS, networks)TRANSCRIPT
Identification of OGGT associated changes
in primary metabolism
Dmitry Grapov, et al.
Study Design
•Overweight women (12-15, obese sedentary)
–14 week diet and exercise intervention
–Weight management and exercise (4 days/week, 30-40 min)
•Endpoints: pre and post intervention
–During Exercise
–During oral glucose tolerance test (OGTT)
•Primary metabolites (n > 300) by GC/TOF
•Clinical panel: insulin, glucose, lipids
•0, 30, 60, 90, 120 minutes
Goals: Identify and Interpret
•Effect on primary metabolite levels by:
–diet and exercise intervention
–exercise
–OGTT (talking about next)
•Analysis/Tools
–ANCOVA
–PCA
–Covariate adjusted PLS modeling
–Mapped Chemical Similarity Network
Exploratory Data Analysis: PCA
no scaling or centering
PCA: Scores and Loadings
no scaling or centering
glucose
219021
PCA: Interpretation
PCA: Data Scaling effect on perceived complexity
no scaling or centering autoscaling
PCA: autoscaled
Goal: Identify OGTT associated changes
•PLS model for time during OGTT
–NIPALS
–LOO cross-validation
•Data pre-treatment:
–Covariate adjustment for intervention effects
–Autoscaled
•Model validation
–Permutation tests
–Training/testing
Intervention adjusted PLS model: Scores
How can we interpret the model within a
biochemical context? (hint: mapped network)
Time 0 – 120 minutes
USE: Chemical Similarity Network (CSN)
•Vertices/nodes =
metabolites
•Edges =
chemical similarity
based on Tanimoto
distances
Mapping results:•Vertex
•Size = importance, |PLS coefficient|
•Color = direction of change, sign of coeff.
•Border = p-value < 0.05 (ANCOVA)
•Edges
•similarity > 70
pink (↑)
cyan (↓)
Making a CSN layout
1. Use pubchem CIDs to get chemical similarity indices
• http://pubchem.ncbi.nlm.nih.gov//score_matrix/score_matrix.cgi
2. Convert square symmetric matrix to edge list
(Metamapp or R)
• Visualize connections (Cytoscape)
To encode results using vertex aesthetics:
3. Make vertex attributes file
4. Map attributes to vertex visual properties
NOW A DEMO