Analysis Overview
Liver Hepatocellular Carcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
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 Liver Hepatocellular Carcinoma (Primary solid tumor cohort) - 21 April 2013. Broad Institute of MIT and Harvard. doi:10.7908/C1Z60M08
Overview
Introduction

This is an overview of Liver Hepatocellular Carcinoma 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 97 tumor samples used in this analysis: 23 significant arm-level results, 26 significant focal amplifications, and 27 significant focal deletions were found.

  • 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 97 samples using the 53 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 11627 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 98 samples and 11627 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 69 samples using the 1500 most variable genes was identified for k = 9 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 69 samples and 1500 genes identified 2 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 96 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 96 samples and 150 miRs identified 2 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 65 arm-level results and 4 clinical features across 72 patients, no significant finding 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 53 arm-level results and 4 clinical features across 72 patients, no significant finding detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 16900 genes and 4 clinical features across 56 samples, statistically thresholded by Q value < 0.05, 3 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 6 different clustering approaches and 4 clinical features across 73 patients, no significant finding detected with P value < 0.05 and Q value < 0.25.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 17848 genes and 4 clinical features across 60 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one genes.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 561 genes and 4 clinical features across 71 samples, statistically thresholded by Q value < 0.05, no clinical feature related to at least one genes.

    • Correlations between copy number and mRNAseq expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are 883, 1995, 2664.1, 3269, 3905, 4548, 5221.9, 5951, 6795, 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 = 68. Number of gene expression samples = 69. Number of methylation samples = 68.

    • Correlation between copy number variations of arm-level result and molecular subtypes
      View Report | Testing the association between copy number variation 71 arm-level results and 6 molecular subtypes across 97 patients, 4 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 53 peak regions and 6 molecular subtypes across 97 patients, 10 significant findings detected with Q value < 0.25.

  • Pathway Analyses

    • PARADIGM pathway analysis of mRNASeq expression data
      View Report | There were 58 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression and copy number data
      View Report | There were 60 significant pathways identified in this analysis.

Methods & Data
Input
  • Summary Report Date = Sat May 25 13:41:42 2013

  • Protection = FALSE