Analysis Overview for Colon/Rectal Adenocarcinoma
Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/Harvard Medical School)
Overview
Introduction

This is the analysis overview for Firehose run "21 March 2012".

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)
  View Report | Significantly mutated genes (q ≤ 0.1): 471

- Copy number analysis (GISTIC2)
  View Report | There were 564 tumor samples used in this analysis: 22 significant arm-level results, 29 significant focal amplifications, and 47 significant focal deletions were found.

- Clustering Analyses

- 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 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 mRNAseq gene expression: consensus NMF
  View Report | The most robust consensus NMF clustering of 83 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 83 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 Methylation: consensus NMF
  View Report | The 1100 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 236 samples and 1100 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 NMF
  View Report | We filtered the data to 150 most variable miRs. Consensus NMF clustering of 255 samples and 150 miRs 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 expression: consensus hierarchical
  View Report | We filtered the data to 150 most variable miRs. Consensus average linkage hierarchical clustering of 255 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.

- Correlation Analyses

- Correlations between copy number and mRNA expression
  View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.0361, 0.0211, 0.07188, 0.1326, 0.2056, 0.28476, 0.3556, 0.4269, 0.51814, respectively.

- Correlation between mRNA expression and DNA methylation
  View Report | The top 25 correlated methylation probe(s) per gene are displayed. Total number of matched samples = 223 Number of gene expression samples = 238 Number of methylation samples = 224

- Other Analyses

- Association of mutation, copy number alteration, and subtype markers with pathways
  View Report | There are 439 genes with significant mutation (Q value <= 0.1) and 362 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 :

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

- PARADIGM pathway analysis of mRNA expression and copy number data
  View Report | There were 45 significant pathways identified in this analysis.

Methods & Data
Input

- Firehose Directory = /xchip/cga1/tcga_gdac_firehose_output

- Run Prefix = analyses__2012_03_21

- Summary Report Date = Fri Apr 20 10:44:33 2012

- Protection = FALSE

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