Analysis Overview
Glioblastoma Multiforme (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C19P2ZP2
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Analysis Overview for Glioblastoma Multiforme (Primary solid tumor cohort) - 23 May 2013. Broad Institute of MIT and Harvard. doi:10.7908/C19P2ZP2
Overview
Introduction

This is an overview of Glioblastoma Multiforme analysis pipelines from Firehose run "23 May 2013".

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: 23 significant arm-level results, 24 significant focal amplifications, and 46 significant focal deletions were found.

    • Mutation Analysis (MutSig v1.5)
      View Report | 

    • Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result)
      View Report | 

    • Mutation Analysis (MutSig v2.0)
      View Report | 

    • Mutation Analysis (MutSigCV v0.9)
      View Report | 

  • Correlations to Clinical Parameters

    • Correlation between aggregated molecular cancer subtypes and selected clinical features
      View Report | Testing the association between subtypes identified by 10 different clustering approaches and 6 clinical features across 573 patients, 2 significant findings detected with P value < 0.05 and Q value < 0.25.

    • Correlation between copy number variation genes (focal) and selected clinical features
      View Report | Testing the association between copy number variation 70 arm-level results and 6 clinical features across 552 patients, 15 significant findings detected with Q value < 0.25.

    • 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 552 patients, 10 significant findings detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 20198 genes and 5 clinical features across 106 samples, statistically thresholded by Q value < 0.05, 1 clinical feature related to at least one genes.

    • Correlation between gene mutation status and selected clinical features
      View Report | Testing the association between mutation status of 13 genes and 6 clinical features across 275 patients, 3 significant findings detected with Q value < 0.25.

    • Correlation between miR expression and clinical features
      View Report | Testing the association between 534 miRs and 6 clinical features across 488 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one miRs.

    • Correlation between mRNA expression and clinical features
      View Report | Testing the association between 12042 genes and 6 clinical features across 523 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 18210 genes and 5 clinical features across 151 samples, statistically thresholded by Q value < 0.05, 1 clinical feature related to at least one genes.

    • 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.

  • Clustering Analyses

    • Clustering of copy number data by focal peak region with log2 ratio: consensus NMF
      View Report | The most robust consensus NMF clustering of 563 samples using the 70 copy number focal regions 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 Methylation: consensus NMF
      View Report | The 8266 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 112 samples and 8266 genes 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.

    • 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 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 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 = 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 mRNAseq gene expression: consensus hierarchical
      View Report | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 153 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 mRNAseq gene expression: consensus NMF
      View Report | The most robust consensus NMF clustering of 153 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 RPPA data: consensus hierarchical
      View Report | 171 proteins were selected. Consensus average linkage hierarchical clustering of 214 samples and 171 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 RPPA data: consensus NMF
      View Report | The most robust consensus NMF clustering of 214 samples using 171 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.

  • 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.

  • Pathway Analyses

    • Association of mutation, copy number alteration, and subtype markers with pathways
      View Report | There are 12 genes with significant mutation (Q value <= 0.1) and 181 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 :

    • HotNet pathway analysis of mutation and copy number data
      View Report | There were 12 significant subnetworks identified in HotNet analysis.

    • PARADIGM pathway analysis of mRNA expression and copy number data
      View Report | There were 31 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNA expression data
      View Report | There were 48 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression and copy number data
      View Report | There were 39 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression data
      View Report | There were 50 significant pathways identified in this analysis.

  • Other Correlation Analyses

    • Correlation between copy number variation genes and molecular subtypes
      View Report | Testing the association between copy number variation of 70 peak regions and 10 molecular subtypes across 563 patients, 117 significant findings detected with Q value < 0.25.

    • Correlation between copy number variations of arm-level result and molecular subtypes
      View Report | Testing the association between copy number variation 79 arm-level results and 10 molecular subtypes across 563 patients, 63 significant findings detected with Q value < 0.25.

    • Correlation between gene mutation status and molecular subtypes
      View Report | Testing the association between mutation status of 13 genes and 10 molecular subtypes across 284 patients, 17 significant findings detected with P value < 0.05 and Q value < 0.25.

    • Correlation between mRNA expression and DNA methylation
      View Report | The top 25 correlated methylation probes per gene are displayed. Total number of matched samples = 47. Number of gene expression samples = 153. Number of methylation samples = 112.

    • Correlations between copy number and miR expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.04754, -0.02288, -0.0027, 0.01812, 0.0408, 0.06424, 0.10074, 0.17386, 0.25122, respectively.

    • Correlations between copy number and mRNA expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.01275, 0.0252, 0.0603, 0.0977, 0.1367, 0.1772, 0.21895, 0.2661, 0.3357, respectively.

    • Correlations between copy number and mRNAseq expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are 933, 1829.8, 2377, 2893, 3399, 3949, 4541, 5221, 6055.6, respectively.

Methods & Data
Input

  • Summary Report Date = Wed Jun 26 16:33:22 2013

  • Protection = FALSE

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