Glioblastoma Multiforme (GBM)

1
Glioblastoma Multiforme (GBM) Subtype Analysis

• Lance Parsons

2
Introduction

• Clinicians (meat readers) determine histological
  categorization Astrocytoma, Oligodendrocytoma,
  Mixed, or Glioblastoma multiforme (GBM)
• GBM patients have poor prognosis, but some surive
  unexpectly long.
• Molecularly and clinically distinct subtypes of
  GBMs

3
Incorporating Biological Knowledge

• Tiers of classification can assist with
  discovery of downstream groups
• Glioma Classification
• Histological Level
• Clinical Level (Survival, Age, etc)
• Transcriptiome (Gene Expression Level)
• Gene Classification
• GO Hierarchy
• Pathway Databases
• Expression Level (Microarray Data)

4
Age and Survival

• Young patients show greater variability in
  survival
• Use this level of the hierarchy to assist in
  downstream analysis.
• Very simple method is to use only the Young
  samples and find the groups within that set of
  samples.

5
Normalization

• Making the numbers comparable
• Log Transform Equalize variance, lineraize data
• Median Center Arrays Correct for differences
  between arrays
• Standardize to unit variance?

6
Noise Filter

• Removing noise from the dataset
• Affymetrix software does some of this with
  Present/Absent calls
• Fold-change filter?
• Other methods?

7
Feature (Gene) Selection

• Find genes highly correlated with patient
  survival, within young sample group.
• Cox Proportional Hazards model
• Regression model that accounts for censored
  data
• Permutation test can improve robustness
• Simple Cox selects 39 genes (permutation pending)

8
Exploration of Results

• The genes we select are statistically significant
  (as dictated by our Cox testing methodology), but
  they may not be biologically or clinically
  significant.
• Initial exploration through hierarchical
  clustering.

9
Clinical Validation

• Kaplan-Meier curves fit the two groups to a
  survival model

10
Biological Validation

• file///C/Documents20and20Settings/Lance/My20D
  ocuments/Research/projects/HenryFord/HFAnalysis-GB
  M-Young_annotations.html