Analysis Overview for Glioblastoma Multiforme
Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/Harvard Medical School)
Overview
Introduction

This is the analysis overview for Firehose run "25 August 2012".

Summary

Note: These results are offered to the community as an additional reference point, enabling a wide range of cancer biologists, clinical investigators, and genome and computational scientists to easily incorporate TCGA into the backdrop of ongoing research. While every effort is made to ensure that Firehose input data and algorithms are of the highest possible quality, these analyses have not been reviewed by domain experts.

Results

- Sequence and Copy Number Analyses

- Copy number analysis (GISTIC2)
  View Report | There were 563 tumor samples used in this analysis: 22 significant arm-level results, 23 significant focal amplifications, and 51 significant focal deletions were found.

- Mutation Analysis (MutSig)
  View Report | MAF used for this analysis: GBM.final_analysis_set.maf

- Clustering Analyses

- Clustering of copy number data: consensus NMF
  View Report | The most robust consensus NMF clustering of 563 samples using the 74 copy number focal regions was identified for k = 4 clusters. We computed the clustering for k = 2 to k = 8 and used the cophenetic correlation coefficient to determine the best solution.

- Clustering of Methylation: consensus NMF
  View Report | The 1146 most variable methylated genes were selected based on variation. The variation cutoff are set for each tumor type empirically by fitting a bimodal distriution. For genes with multiple methylation probes, we chose the most variable one to represent the gene. Consensus NMF clustering of 287 samples and 1146 genes identified 3 subtypes with the stability of the clustering increasing for k = 2 to k = 8 and the average silhouette width calculation for selecting the robust clusters.

- Clustering of RPPA data: consensus NMF
  View Report | The most robust consensus NMF clustering of 214 samples using the 150 most variable proteins was identified for k = 4 clusters. We computed the clustering for k = 2 to k = 8 and used the cophenetic correlation coefficient to determine the best solution.

- Clustering of RPPA data: consensus hierarchical
  View Report | The 150 most variable proteins were selected. Consensus average linkage hierarchical clustering of 214 samples and 150 proteins identified 3 subtypes with the stability of the clustering increasing for k = 2 to k = 8 and the average silhouette width calculation for selecting the robust clusters.

- Clustering of mRNA expression: consensus NMF
  View Report | The most robust consensus NMF clustering of 529 samples using the 1500 most variable genes was identified for k = 3 clusters. We computed the clustering for k = 2 to k = 8 and used the cophenetic correlation coefficient to determine the best solution.

- Clustering of mRNA expression: consensus hierarchical
  View Report | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 529 samples and 1500 genes identified 3 subtypes with the stability of the clustering increasing for k = 2 to k = 8 and the average silhouette width calculation for selecting the robust clusters.

- Clustering of miR expression: consensus NMF
  View Report | We filtered the data to 150 most variable miRs. Consensus NMF clustering of 491 samples and 150 miRs identified 4 subtypes with the stability of the clustering increasing for k = 2 to k = 8 and the average silhouette width calculation for selecting the robust clusters.

- Clustering of miR expression: consensus hierarchical
  View Report | We filtered the data to 150 most variable miRs. Consensus average linkage hierarchical clustering of 491 samples and 150 miRs identified 3 subtypes with the stability of the clustering increasing for k = 2 to k = 8 and the average silhouette width calculation for selecting the robust clusters.

- Correlation Analyses

- Correlation between copy number variations of arm-level result and selected clinical features
  View Report | Testing the association between copy number variation 79 arm-level results and 6 clinical features across 544 patients, 10 significant findings detected with Q value < 0.25.

- Correlation between copy number variation genes and selected clinical features
  View Report | Testing the association between copy number variation of 74 peak regions and 6 clinical features across 544 patients, 15 significant findings detected with Q value < 0.25.

- Correlation between gene methylation status and clinical features
  View Report | Testing the association between 12759 genes and 6 clinical features across 280 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

- Correlation between molecular cancer subtypes and selected clinical features
  View Report | Testing the association between subtypes identified by 5 different clustering approaches and 6 clinical features across 527 patients, 7 significant findings detected with P value < 0.05.

- Correlation between gene mutation status and selected clinical features
  View Report | Testing the association between mutation status of 338 genes and 6 clinical features across 269 patients, 39 significant findings detected with Q value < 0.25.

- Correlation between RPPA expression and clinical features
  View Report | Testing the association between 171 genes and 6 clinical features across 210 samples, statistically thresholded by Q value < 0.05, 1 clinical feature related to at least one genes.

- Correlation between mRNA expression and clinical features
  View Report | Testing the association between 12042 genes and 6 clinical features across 519 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

- Correlation between miR expression and clinical features
  View Report | Testing the association between 534 miRs and 6 clinical features across 482 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one miRs.

- Correlations between copy number and mRNA expression
  View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.02419, 0.0155, 0.05483, 0.1036, 0.1552, 0.20396, 0.25117, 0.30294, 0.37249, respectively.

- Correlations between copy number and miR expression
  View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.0553, -0.0142, 0.00515, 0.02166, 0.0401, 0.07766, 0.13265, 0.2091, 0.2699, respectively.

- Correlation between mRNA expression and DNA methylation
  View Report | The top 25 correlated methylation probes per gene are displayed. Total number of matched samples = 279. Number of gene expression samples = 529. Number of methylation samples = 287.

- Other Analyses

- Association of mutation, copy number alteration, and subtype markers with pathways
  View Report | There are 222 genes with significant mutation (Q value <= 0.1) and 159 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 2000 for subtype 1, 2000 for subtype 2, 2000 for subtype 3. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

- PARADIGM pathway analysis of mRNA expression data
  View Report | There were 69 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNA expression and copy number data
  View Report | There were 99 significant pathways identified in this analysis.

- Identification of putative miR direct targets
  View Report | This pipeline use a relevance network approach to infer putative miR:mRNA regulatory connections. All miR:mRNA pairs that have correlations < -0.3 and have predicted interactions in three sequence prediction databases (Miranda, Pictar, Targetscan) define the final network.

Methods & Data
Input

- Run Prefix = analyses__2012_08_25

- Summary Report Date = Thu Sep 27 11:59:01 2012

- Protection = FALSE

Copyright © 2012 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle