Analysis Overview
Colon/Rectal Adenocarcinoma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1N58JJH
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 Colon/Rectal Adenocarcinoma (Primary solid tumor cohort) - 22 February 2013. Broad Institute of MIT and Harvard. doi:10.7908/C1N58JJH
Overview
Introduction

This is an overview of Colon/Rectal Adenocarcinoma 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 575 tumor samples used in this analysis: 24 significant arm-level results, 28 significant focal amplifications, and 47 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 75 different clustering approaches and 10 clinical features across 575 patients, 53 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 78 different clustering approaches and 10 clinical features across 575 patients, 25 significant findings detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 16969 genes and 9 clinical features across 35 samples, statistically thresholded by Q value < 0.05, 3 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 209 genes and 9 clinical features across 224 patients, 2 significant findings detected with Q value < 0.25.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 420 genes and 10 clinical features across 550 samples, statistically thresholded by Q value < 0.05, 8 clinical features related to at least one genes.

    • Correlation between mRNA expression and clinical features
      View Report | Testing the association between 17814 genes and 9 clinical features across 224 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 17880 genes and 9 clinical features across 264 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

    • Correlation between RPPA expression and clinical features
      View Report | Testing the association between 171 genes and 10 clinical features across 399 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 575 samples using the 75 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 6372 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 350 samples and 6372 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 expression: consensus hierarchical
      View Report | We filtered the data to 150 most variable miRs. Consensus average linkage hierarchical clustering of 551 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 551 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 224 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 224 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 264 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 264 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 RPPA data: consensus hierarchical
      View Report | The 150 most variable proteins were selected. Consensus average linkage hierarchical clustering of 399 samples and 150 proteins 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 RPPA data: consensus NMF
      View Report | The most robust consensus NMF clustering of 399 samples using the 150 most variable 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

    • Correlate_Clinical_vs_Molecular_Signatures
      View Report | Testing the association between subtypes identified by 10 different clustering approaches and 10 clinical features across 588 patients, 15 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 120 genes with significant mutation (Q value <= 0.1) and 555 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 81 significant subnetworks identified in HotNet analysis.

    • PARADIGM pathway analysis of mRNA expression and copy number data
      View Report | There were 30 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNA expression data
      View Report | There were 46 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression and copy number data
      View Report | There were 30 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression data
      View Report | There were 44 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 75 peak regions and 10 molecular subtypes across 575 patients, 151 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 78 arm-level results and 10 molecular subtypes across 575 patients, 86 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 209 genes and 10 molecular subtypes across 224 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 = 37. Number of gene expression samples = 264. Number of methylation samples = 37.

    • Correlations between copy number and mRNA expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.035, 0.01662, 0.0669, 0.1233, 0.1906, 0.2619, 0.33107, 0.40528, 0.4924, 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 848, 1562, 2073, 2590.2, 3090.5, 3581.8, 4086, 4664, 5422.7, respectively.

Methods & Data
Input

  • Summary Report Date = Mon Aug 5 19:19:59 2013

  • Protection = FALSE

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