Analysis Overview
Skin Cutaneous Melanoma (Metastatic)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
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 Skin Cutaneous Melanoma (Metastatic cohort) - 23 May 2013. Broad Institute of MIT and Harvard. doi:10.7908/C16H4FHQ
Overview
Introduction

This is an overview of Skin Cutaneous Melanoma analysis pipelines from Firehose run "23 May 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 260 tumor samples used in this analysis: 22 significant arm-level results, 22 significant focal amplifications, and 32 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 | 

  • Correlations to Clinical Parameters

    • Correlation between aggregated molecular cancer subtypes and selected clinical features
      View Report | Testing the association between subtypes identified by 10 different clustering approaches and 8 clinical features across 180 patients, 4 significant findings detected with P value < 0.05 and Q value < 0.25.

    • Correlation between copy number variation genes (focal) and selected clinical features
      View Report | Testing the association between copy number variation 54 arm-level results and 8 clinical features across 180 patients, no significant finding 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 77 arm-level results and 8 clinical features across 180 patients, 2 significant findings detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 19639 genes and 7 clinical features across 177 samples, statistically thresholded by Q value < 0.05, 6 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 87 genes and 8 clinical features across 161 patients, 9 significant findings detected with Q value < 0.25.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 602 genes and 7 clinical features across 169 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 18090 genes and 7 clinical features across 171 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 175 genes and 7 clinical features across 109 samples, statistically thresholded by Q value < 0.05, 3 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 260 samples using the 54 copy number focal regions 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 Methylation: consensus NMF
      View Report | The 11484 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 260 samples and 11484 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 mature expression: consensus hierarchical
      View Report | We filtered the data to 178 most variable miRs. Consensus average linkage hierarchical clustering of 239 samples and 178 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 178 most variable miRs. Consensus NMF clustering of 239 samples and 178 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 239 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 239 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 mRNAseq gene expression: consensus hierarchical
      View Report | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 241 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 241 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 | 175 proteins were selected. Consensus average linkage hierarchical clustering of 143 samples and 175 proteins 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.

    • Clustering of RPPA data: consensus NMF
      View Report | The most robust consensus NMF clustering of 143 samples using 175 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.

  • Pathway Analyses

    • HotNet pathway analysis of mutation and copy number data
      View Report | There were 47 significant subnetworks identified in HotNet analysis.

    • PARADIGM pathway analysis of mRNASeq expression and copy number data
      View Report | There were 62 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression data
      View Report | There were 61 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 54 peak regions and 10 molecular subtypes across 260 patients, 33 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 260 patients, 40 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 89 genes and 10 molecular subtypes across 228 patients, one significant finding 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 = 241. Number of gene expression samples = 241. Number of methylation samples = 260.

    • Correlations between copy number and mRNAseq expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are 971.8, 1685, 2238, 2826, 3432, 4069, 4732, 5409.4, 6169, respectively.

Methods & Data
Input
  • Summary Report Date = Wed Jun 26 18:37:32 2013

  • Protection = FALSE