Analysis Overview
Colon Adenocarcinoma (Primary solid tumor)
21 April 2013 | analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1GH9FVK
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 Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013. Broad Institute of MIT and Harvard. doi:10.7908/C1GH9FVK
Overview
Introduction

This is an overview of Colon Adenocarcinoma 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 413 tumor samples used in this analysis: 23 significant arm-level results, 24 significant focal amplifications, and 44 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 413 samples using the 68 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 6192 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 255 samples and 6192 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 RPPA data: consensus NMF
  View Report | The most robust consensus NMF clustering of 331 samples using 171 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.

- Clustering of RPPA data: consensus hierarchical
  View Report | 171 proteins were selected. Consensus average linkage hierarchical clustering of 331 samples and 171 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 mRNA expression: consensus NMF
  View Report | The most robust consensus NMF clustering of 153 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 mRNA expression: consensus hierarchical
  View Report | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 153 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 192 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 192 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 408 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 408 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 76 arm-level results and 11 clinical features across 413 patients, 18 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 68 arm-level results and 11 clinical features across 413 patients, 34 significant findings detected with Q value < 0.25.

- Correlation between gene methylation status and clinical features
  View Report | Testing the association between 17130 genes and 10 clinical features across 189 samples, statistically thresholded by Q value < 0.05, 6 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 11 clinical features across 422 patients, 12 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 120 genes and 10 clinical features across 155 patients, 23 significant findings detected with Q value < 0.25.

- Correlation between RPPA expression and clinical features
  View Report | Testing the association between 171 genes and 11 clinical features across 331 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

- Correlation between mRNA expression and clinical features
  View Report | Testing the association between 17814 genes and 10 clinical features across 153 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 18041 genes and 10 clinical features across 192 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

- Correlation between miRseq expression and clinical features
  View Report | Testing the association between 417 genes and 11 clinical features across 407 samples, statistically thresholded by Q value < 0.05, 6 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 -0.05139, 0.0114, 0.06453, 0.1214, 0.18545, 0.2609, 0.33347, 0.41328, 0.50719, 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 753.5, 1650, 2241, 2871, 3532, 4213, 4870, 5551, 6410.5, 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 = 189. Number of gene expression samples = 192. Number of methylation samples = 189.

- Correlation between copy number variations of arm-level result and molecular subtypes
  View Report | Testing the association between copy number variation 76 arm-level results and 10 molecular subtypes across 413 patients, 78 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 68 peak regions and 10 molecular subtypes across 413 patients, 150 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 120 genes and 7 molecular subtypes across 155 patients, 12 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 61 genes with significant mutation (Q value <= 0.1) and 360 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 35 significant subnetworks identified in HotNet analysis.

- PARADIGM pathway analysis of mRNASeq expression data
  View Report | There were 51 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNASeq expression and copy number data
  View Report | There were 50 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNA expression data
  View Report | There were 48 significant pathways identified in this analysis.

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

Methods & Data
Input

- Summary Report Date = Sat May 25 13:17:48 2013

- Protection = FALSE

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