Analysis Overview
Breast Invasive Carcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1GT5K3Z
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 Breast Invasive Carcinoma (Primary solid tumor cohort) - 21 April 2013. Broad Institute of MIT and Harvard. doi:10.7908/C1GT5K3Z
Overview
Introduction

This is an overview of Breast Invasive Carcinoma analysis pipelines from Firehose run "21 April 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 913 tumor samples used in this analysis: 26 significant arm-level results, 27 significant focal amplifications, and 37 significant focal deletions were found.

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

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

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

  • 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 913 samples using the 64 copy number focal regions 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.

    • Clustering of Methylation: consensus NMF
      View Report | The 4836 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 615 samples and 4836 genes identified 6 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 408 samples using 142 proteins 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 | 142 proteins were selected. Consensus average linkage hierarchical clustering of 408 samples and 142 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 526 samples using the 1500 most variable genes was identified for k = 8 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 526 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 842 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 842 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 miRseq precursor expression: consensus NMF
      View Report | We filtered the data to 150 most variable miRs. Consensus NMF clustering of 896 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 hierarchical
      View Report | We filtered the data to 150 most variable miRs. Consensus average linkage hierarchical clustering of 896 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 80 arm-level results and 9 clinical features across 857 patients, 3 significant findings detected with Q value < 0.25.

    • Correlation between copy number variation genes (focal) and selected clinical features
      View Report | Testing the association between copy number variation 64 arm-level results and 9 clinical features across 857 patients, 3 significant findings detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 17320 genes and 8 clinical features across 530 samples, statistically thresholded by Q value < 0.05, 7 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 10 different clustering approaches and 9 clinical features across 873 patients, 7 significant findings detected with P value < 0.05 and Q value < 0.25.

    • Correlation between gene mutation status and selected clinical features
      View Report | Testing the association between mutation status of 91 genes and 9 clinical features across 772 patients, 16 significant findings detected with Q value < 0.25.

    • Correlation between RPPA expression and clinical features
      View Report | Testing the association between 142 genes and 8 clinical features across 408 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one genes.

    • Correlation between mRNA expression and clinical features
      View Report | Testing the association between 17814 genes and 8 clinical features across 526 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 18256 genes and 8 clinical features across 837 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 496 genes and 8 clinical features across 852 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

    • Correlations between copy number and mRNA expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.0076, 0.0407, 0.0933, 0.15704, 0.23725, 0.32466, 0.4075, 0.48208, 0.56678, 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 1015.9, 1613, 2154, 2757, 3446, 4201, 4955, 5651.2, 6410.1, 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 = 537. Number of gene expression samples = 842. Number of methylation samples = 537.

    • Correlation between copy number variations of arm-level result and molecular subtypes
      View Report | Testing the association between copy number variation 80 arm-level results and 10 molecular subtypes across 913 patients, 374 significant findings detected with Q value < 0.25.

    • Correlation between copy number variation genes and molecular subtypes
      View Report | Testing the association between copy number variation of 64 peak regions and 10 molecular subtypes across 913 patients, 463 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 91 genes and 10 molecular subtypes across 772 patients, 44 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 43 genes with significant mutation (Q value <= 0.1) and 195 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

    • PARADIGM pathway analysis of mRNASeq 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 53 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNA expression data
      View Report | There were 54 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNA expression and copy number data
      View Report | There were 53 significant pathways identified in this analysis.

Methods & Data
Input

  • Summary Report Date = Sat May 25 13:12:19 2013

  • Protection = FALSE

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