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