Analysis Overview
Liver Hepatocellular Carcinoma (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1DV1H74
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) - 23 September 2013. Broad Institute of MIT and Harvard. doi:10.7908/C1DV1H74
Overview
Introduction

This is an overview of Liver Hepatocellular Carcinoma analysis pipelines from Firehose run "23 September 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

- SNP6 Copy number analysis (GISTIC2)
  View Report | There were 139 tumor samples used in this analysis: 25 significant arm-level results, 25 significant focal amplifications, and 28 significant focal deletions were found.

- Correlations to Clinical Parameters

- Correlation between aggregated molecular cancer subtypes and selected clinical features
  View Report | Testing the association between subtypes identified by 8 different clustering approaches and 8 clinical features across 119 patients, 4 significant findings detected with P value < 0.05 and Q value < 0.25.

- Correlation between copy number variation genes (focal events) and selected clinical features
  View Report | Testing the association between copy number variation 53 focal events and 8 clinical features across 117 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 80 arm-level events and 8 clinical features across 117 patients, one significant finding detected with Q value < 0.25.

- Correlation between gene methylation status and clinical features
  View Report | Testing the association between 19657 genes and 8 clinical features across 107 samples, statistically thresholded by Q value < 0.05, 8 clinical features related to at least one genes.

- Correlation between miRseq expression and clinical features
  View Report | Testing the association between 551 genes and 8 clinical features across 114 samples, statistically thresholded by Q value < 0.05, 1 clinical feature related to at least one genes.

- Correlation between mRNAseq expression and clinical features
  View Report | Testing the association between 17758 genes and 8 clinical features across 115 samples, statistically thresholded by Q value < 0.05, 7 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 139 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 11825 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 125 samples and 11825 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 246 most variable miRs. Consensus average linkage hierarchical clustering of 136 samples and 246 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 246 most variable miRs. Consensus NMF clustering of 136 samples and 246 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 136 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 136 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.

- Clustering of mRNAseq gene expression: consensus hierarchical
  View Report | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 134 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 134 samples using the 1500 most variable genes was identified for k = 5 clusters. We computed the clustering for k = 2 to k = 8 and used the cophenetic correlation coefficient to determine the best solution.

- Pathway Analyses

- PARADIGM pathway analysis of mRNASeq expression and copy number data
  View Report | There were 66 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNASeq expression data
  View Report | There were 64 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 53 peak regions and 8 molecular subtypes across 139 patients, 20 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 77 arm-level results and 8 molecular subtypes across 139 patients, 5 significant findings detected with 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 = 121. Number of gene expression samples = 134. Number of methylation samples = 125.

- 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, 1847, 2414, 2965, 3510.5, 4123, 4789, 5521, 6335.5, respectively.

Methods & Data
Input

- Summary Report Date = Mon Oct 21 15:09:39 2013

- Protection = FALSE

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