Analysis Overview
Breast Invasive Carcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1028PX5
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Analysis Overview for Breast Invasive Carcinoma (Primary solid tumor cohort) - 15 January 2014. Broad Institute of MIT and Harvard. doi:10.7908/C1028PX5
Overview
Introduction

This is an overview of Breast Invasive Carcinoma analysis pipelines from Firehose run "15 January 2014".

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

    • LowPass Copy number analysis (GISTIC2)
      View Report | There were 19 tumor samples used in this analysis: 15 significant arm-level results, 2 significant focal amplifications, and 2 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 | 

    • Mutation Assessor
      View Report | 

    • SNP6 Copy number analysis (GISTIC2)
      View Report | There were 1007 tumor samples used in this analysis: 28 significant arm-level results, 28 significant focal amplifications, and 40 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 10 clinical features across 975 patients, 43 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 68 focal events and 10 clinical features across 957 patients, 39 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 80 arm-level events and 10 clinical features across 957 patients, 21 significant findings detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 19956 genes and 10 clinical features across 652 samples, statistically thresholded by Q value < 0.05, 8 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 73 genes and 10 clinical features across 943 patients, 20 significant findings detected with Q value < 0.25.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 497 miRs and 10 clinical features across 954 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one miRs.

    • Correlation between mRNA expression and clinical features
      View Report | Testing the association between 17814 genes and 10 clinical features across 526 samples, statistically thresholded by Q value < 0.05, 8 clinical features related to at least one genes.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 18284 genes and 10 clinical features across 969 samples, statistically thresholded by Q value < 0.05, 9 clinical features related to at least one genes.

    • Correlation between RPPA expression and clinical features
      View Report | Testing the association between 142 genes and 10 clinical features across 408 samples, statistically thresholded by Q value < 0.05, 6 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 1007 samples using the 68 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 copy number data by peak region with threshold value: consensus NMF
      View Report | The most robust consensus NMF clustering of 1007 samples using the 68 copy number focal regions was identified for k = 7 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 5015 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 711 samples and 5015 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 miRseq mature expression: consensus hierarchical
      View Report | We filtered the data to 258 most variable miRs. Consensus average linkage hierarchical clustering of 673 samples and 258 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 258 most variable miRs. Consensus NMF clustering of 673 samples and 258 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 995 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 995 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 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 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 mRNAseq gene expression: consensus hierarchical
      View Report | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 1019 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 1019 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 | 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 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.

  • Pathway Analyses

    • Association of mutation, copy number alteration, and subtype markers with pathways
      View Report | There are 53 genes with significant mutation (Q value <= 0.1) and 230 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 mRNA expression and copy number data
      View Report | There were 52 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 mRNASeq expression and copy number data
      View Report | There were 57 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression data
      View Report | There were 55 significant pathways identified in this analysis.

  • Other Correlation Analyses

    • Correlation between copy number variation genes (focal events) and molecular subtypes
      View Report | Testing the association between copy number variation 40 focal events and 12 molecular subtypes across 1007 patients, 414 significant findings detected with P value < 0.05 and 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 80 arm-level events and 12 molecular subtypes across 1007 patients, 555 significant findings detected with P value < 0.05 and Q value < 0.25.

    • Correlation between gene mutation status and molecular subtypes
      View Report | Testing the association between mutation status of 73 genes and 12 molecular subtypes across 975 patients, 53 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 = 691. Number of gene expression samples = 1019. Number of methylation samples = 711.

    • Correlations between copy number and mRNA expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.0067, 0.04192, 0.0935, 0.1584, 0.2402, 0.32916, 0.41387, 0.48948, 0.5751, 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 1040, 1614.4, 2144, 2728, 3367.5, 4072, 4773.9, 5465.6, 6258, respectively.

Methods & Data
Input

  • Summary Report Date = Fri Feb 28 11:56:47 2014

  • Protection = FALSE

Copyright © 2014 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle