Analysis Overview
Brain Lower Grade Glioma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1VM49H0
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 Brain Lower Grade Glioma (Primary solid tumor cohort) - 22 February 2013. Broad Institute of MIT and Harvard. doi:10.7908/C1VM49H0
Overview
Introduction

This is an overview of Brain Lower Grade Glioma analysis pipelines from Firehose run "22 February 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 220 tumor samples used in this analysis: 21 significant arm-level results, 15 significant focal amplifications, and 28 significant focal deletions were found.

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

    • Mutation Analysis (MutSig vS2N)
      View Report | 

    • Mutation Analysis (MutSigCV v0.6)
      View Report | 

  • Correlations to Clinical Parameters

    • Correlation between copy number variation genes (focal) and selected clinical features
      View Report | Testing the association between subtypes identified by 43 different clustering approaches and 6 clinical features across 207 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 subtypes identified by 50 different clustering approaches and 6 clinical features across 207 patients, 17 significant findings detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 17401 genes and 6 clinical features across 169 samples, statistically thresholded by Q value < 0.05, 4 clinical features related to at least one genes.

    • Correlation between gene mutation status and selected clinical features
      View Report | Testing the association between mutation status of 33 genes and 6 clinical features across 168 patients, 9 significant findings detected with Q value < 0.25.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 564 genes and 6 clinical features across 207 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

    • Correlation between mRNA expression and clinical features
      View Report | Testing the association between 17814 genes and 6 clinical features across 27 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one genes.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 18364 genes and 6 clinical features across 206 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

  • Clustering Analyses

    • Clustering of copy number data: consensus NMF
      View Report | The most robust consensus NMF clustering of 220 samples using the 43 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 8481 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 176 samples and 8481 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 miRseq expression: consensus hierarchical
      View Report | We filtered the data to 150 most variable miRs. Consensus average linkage hierarchical clustering of 221 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 miRseq expression: consensus NMF
      View Report | We filtered the data to 150 most variable miRs. Consensus NMF clustering of 221 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 27 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 27 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 mRNAseq gene expression: consensus hierarchical
      View Report | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 220 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 220 samples using the 1500 most variable genes was identified for k = 5 clusters. We computed the clustering for k = 2 to k = 8 and used the cophenetic correlation coefficient to determine the best solution.

  • Other Analyses

    • Correlate_Clinical_vs_Molecular_Signatures
      View Report | Testing the association between subtypes identified by 8 different clustering approaches and 6 clinical features across 208 patients, 14 significant findings detected with P value < 0.05 and Q value < 0.25.

  • Pathway Analyses

    • Association of mutation, copy number alteration, and subtype markers with pathways
      View Report | There are 14 genes with significant mutation (Q value <= 0.1) and 470 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 245 for subtype 1, 245 for subtype 2, 245 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 45 significant subnetworks identified in HotNet analysis.

    • PARADIGM pathway analysis of mRNA expression and copy number data
      View Report | There were 25 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNA expression data
      View Report | There were 37 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 60 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 43 peak regions and 8 molecular subtypes across 220 patients, 62 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 51 arm-level results and 8 molecular subtypes across 220 patients, 49 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 33 genes and 8 molecular subtypes across 170 patients, 36 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 = 174. Number of gene expression samples = 220. Number of methylation samples = 174.

    • Correlations between copy number and mRNA expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.1572, -0.0457, 0.0402, 0.1179, 0.19345, 0.2741, 0.36144, 0.46754, 0.6038, 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 720.6, 1695, 2187, 2648, 3118, 3659, 4275, 4988.8, 5960.4, respectively.

Methods & Data
Input

  • Summary Report Date = Mon Aug 5 20:01:43 2013

  • Protection = FALSE

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