Interpreting Metabolomic Profiles using Unbiased Pathway ...
Metabolomic analysis during glucose infusion
description
Transcript of Metabolomic analysis during glucose infusion
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