Analysis Overview
Brain Lower Grade Glioma (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1MG7MSW
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) - 23 September 2013. Broad Institute of MIT and Harvard. doi:10.7908/C1MG7MSW
Overview
Introduction

This is an overview of Brain Lower Grade Glioma analysis pipelines from Firehose run "23 September 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

- Mutation Analysis (MutSig v1.5)
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- Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result)
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- Mutation Analysis (MutSig v2.0)
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- Mutation Analysis (MutSigCV v0.9)
  View Report |

- Mutation Assessor
  View Report |

- SNP6 Copy number analysis (GISTIC2)
  View Report | There were 269 tumor samples used in this analysis: 21 significant arm-level results, 20 significant focal amplifications, and 28 significant focal deletions were found.

- Correlations to Clinical Parameters

- Correlation between aggregated molecular cancer subtypes and selected clinical features
  View Report | Testing the association between subtypes identified by 12 different clustering approaches and 6 clinical features across 241 patients, 21 significant findings detected with P value < 0.05 and Q value < 0.25.

- Correlation between copy number variation genes (focal events) and selected clinical features
  View Report | Testing the association between copy number variation 48 focal events and 6 clinical features across 229 patients, 14 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 71 arm-level events and 6 clinical features across 229 patients, 19 significant findings detected with Q value < 0.25.

- Correlation between gene methylation status and clinical features
  View Report | Testing the association between 20103 genes and 6 clinical features across 233 samples, statistically thresholded by Q value < 0.05, 5 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 18 genes and 6 clinical features across 210 patients, 9 significant findings detected with Q value < 0.25.

- Correlation between miRseq expression and clinical features
  View Report | Testing the association between 542 genes and 6 clinical features across 240 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 18324 genes and 6 clinical features across 231 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

- Correlation between RPPA expression and clinical features
  View Report | Testing the association between 189 genes and 6 clinical features across 222 samples, statistically thresholded by Q value < 0.05, 4 clinical features 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 269 samples using the 48 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 8446 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 291 samples and 8446 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 mature expression: consensus hierarchical
  View Report | We filtered the data to 247 most variable miRs. Consensus average linkage hierarchical clustering of 295 samples and 247 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 mature expression: consensus NMF
  View Report | We filtered the data to 247 most variable miRs. Consensus NMF clustering of 295 samples and 247 miRs identified 8 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 precursor expression: consensus hierarchical
  View Report | We filtered the data to 150 most variable miRs. Consensus average linkage hierarchical clustering of 295 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 precursor expression: consensus NMF
  View Report | We filtered the data to 150 most variable miRs. Consensus NMF clustering of 295 samples and 150 miRs identified 5 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 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 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 271 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 271 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 | 189 proteins were selected. Consensus average linkage hierarchical clustering of 258 samples and 189 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 258 samples using 189 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.

- Pathway Analyses

- Association of mutation, copy number alteration, and subtype markers with pathways
  View Report | There are 19 genes with significant mutation (Q value <= 0.1) and 497 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 713 for subtype 1, 713 for subtype 2, 713 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 117 significant subnetworks identified in HotNet analysis.

- PARADIGM pathway analysis of mRNA expression and copy number data
  View Report | There were 32 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNA expression data
  View Report | There were 39 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNASeq expression and copy number data
  View Report | There were 56 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNASeq expression data
  View Report | There were 65 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 48 peak regions and 12 molecular subtypes across 269 patients, 116 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 60 arm-level results and 12 molecular subtypes across 269 patients, 98 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 18 genes and 12 molecular subtypes across 220 patients, 38 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 = 266. Number of gene expression samples = 271. Number of methylation samples = 291.

- Correlations between copy number and mRNA expression
  View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.15789, -0.04678, 0.0404, 0.1187, 0.19565, 0.2784, 0.36877, 0.4771, 0.6207, 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 763, 1738, 2223, 2691, 3158.5, 3702, 4315, 5024, 5960, respectively.

Methods & Data
Input

- Summary Report Date = Mon Oct 21 15:07:42 2013

- Protection = FALSE

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