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 April 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

    • Mutation Analysis (MutSig)
      View Report | Significantly mutated genes (q ≤ 0.1): 251

    • Copy number analysis (GISTIC2)
      View Report | There were 537 tumor samples used in this analysis: 25 significant arm-level results, 14 significant focal amplifications, and 51 significant focal deletions were found.

  • Clustering Analyses

    • 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 Methylation: consensus NMF
      View Report | The 1139 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 1139 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

    • Correlations between copy number and mRNA expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.0046, 0.0335, 0.0702, 0.11046, 0.1566, 0.2039, 0.251, 0.30614, 0.38091, 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 -0.05784, -0.02672, -0.00676, 0.01442, 0.0362, 0.0664, 0.11348, 0.19932, 0.27524, respectively.

    • Correlation between mRNA expression and DNA methylation
      View Report | The top 25 correlated methylation probe(s) per gene are displayed. Total number of matched samples = 279 Number of gene expression samples = 289 Number of methylation samples = 529

  • Other Analyses

    • 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.

    • Association of mutation, copy number alteration, and subtype markers with pathways
      View Report | There are 250 genes with significant mutation (Q value <= 0.1) and 156 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 71 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNA expression and copy number data
      View Report | There were 98 significant pathways identified in this analysis.

Methods & Data
Input

  • Firehose Directory = /local/cga-fh/tcga-gdac

  • Run Prefix = analyses__2012_04_25

  • Summary Report Date = Thu May 24 07:26:18 2012

  • Protection = FALSE

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