Glioblastoma Multiforme (GBM) – Subtype Analysis Lance Parsons

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

Tumor Type AstroMixedOligoGBM Age YoungMediumOld 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) Survival ShortLong Glioma Subtypes ABC Gene Subset Expression XYX

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.

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

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

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)

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.

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

Biological Validation file:///C:/Documents%20and%20Settings/L ance/My%20Documents/Research/project s/HenryFord/HFAnalysis-GBM- Young_annotations.htmlfile:///C:/Documents%20and%20Settings/L ance/My%20Documents/Research/project s/HenryFord/HFAnalysis-GBM- Young_annotations.html