Analysis Overview
Kidney Renal Clear Cell Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1G44P68
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Analysis Overview for Kidney Renal Clear Cell Carcinoma (Primary solid tumor cohort) - 17 October 2014. Broad Institute of MIT and Harvard. doi:10.7908/C1G44P68
Overview
Introduction

This is an overview of Kidney Renal Clear Cell Carcinoma analysis pipelines from Firehose run "17 October 2014".

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

    • Analysis of mutagenesis by APOBEC cytidine deaminases (P-MACD).
      View Report | There are 491 tumor samples in this analysis. The Benjamini-Hochberg-corrected p-value for enrichment of the APOBEC mutation signature in 0 samples is <=0.05. Out of these, 0 have enrichment values >2, which implies that in such samples at least 50% of APOBEC signature mutations have been in fact made by APOBEC enzyme(s).

    • CHASM 1.0.5 (Cancer-Specific High-throughput Annotation of Somatic Mutations)
      View Report | There are 16743 mutations identified by MuTect and 1359 mutations with significant functional impact at BHFDR <= 0.25.

    • Mutation Analysis (MutSig 2CV v3.1)
      View Report | 

    • Mutation Analysis (MutSig v1.5)
      View Report | 

    • Mutation Analysis (MutSig v2.0)
      View Report | 

    • Mutation Analysis (MutSigCV v0.9)
      View Report | 

    • Mutation Assessor
      View Report | 

    • SNP6 Copy number analysis (GISTIC2)
      View Report | There were 528 tumor samples used in this analysis: 28 significant arm-level results, 12 significant focal amplifications, and 18 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 12 different clustering approaches and 11 clinical features across 525 patients, 39 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 30 focal events and 11 clinical features across 516 patients, 21 significant findings 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 79 arm-level events and 11 clinical features across 516 patients, 21 significant findings detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 20123 genes and 11 clinical features across 307 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 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 29 genes and 10 clinical features across 417 patients, 2 significant findings detected with Q value < 0.25.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 462 miRs and 11 clinical features across 504 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one miRs.

    • Correlation between mRNA expression and clinical features
      View Report | Testing the association between 17814 genes and 9 clinical features across 72 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 4 clinical features related to at least one genes.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 18273 genes and 11 clinical features across 519 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

    • Correlation between mutation rate and clinical features
      View Report | Testing the association between 2 variables and 11 clinical features across 417 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 4 clinical features related to at least one variables.

    • Correlation between RPPA expression and clinical features
      View Report | Testing the association between 155 genes and 10 clinical features across 454 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 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 528 samples using the 30 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 copy number data by peak region with threshold value: consensus NMF
      View Report | The most robust consensus NMF clustering of 528 samples using the 30 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 1997 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 319 samples and 1997 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 | Median absolute deviation (MAD) was used to select 647 most variable miRs. Consensus ward linkage hierarchical clustering of 144 samples and 647 miRs identified 3 subtypes with the stability of the clustering increasing for k = 2 to k = 10.

    • Clustering of miRseq mature expression: consensus NMF
      View Report | We filtered the data to 647 most variable miRs. Consensus NMF clustering of 144 samples and 647 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 precursor expression: consensus hierarchical
      View Report | Median absolute deviation (MAD) was used to select 115 most variable miRs. Consensus ward linkage hierarchical clustering of 516 samples and 115 miRs identified 4 subtypes with the stability of the clustering increasing for k = 2 to k = 10.

    • Clustering of miRseq precursor expression: consensus NMF
      View Report | We filtered the data to 150 most variable miRs. Consensus NMF clustering of 516 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 mRNA expression: consensus hierarchical
      View Report | Median absolute deviation (MAD) was used to select 1500 most variable genes. Consensus ward linkage hierarchical clustering of 72 samples and 1500 genes identified 7 subtypes with the stability of the clustering increasing for k = 2 to k = 10.

    • Clustering of mRNA expression: consensus NMF
      View Report | The most robust consensus NMF clustering of 72 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 mRNAseq gene expression: consensus hierarchical
      View Report | Median absolute deviation (MAD) was used to select 1500 most variable genes. Consensus ward linkage hierarchical clustering of 531 samples and 1500 genes identified 3 subtypes with the stability of the clustering increasing for k = 2 to k = 10.

    • Clustering of mRNAseq gene expression: consensus NMF
      View Report | The most robust consensus NMF clustering of 531 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 | Median absolute deviation (MAD) was used to select 155 most variable proteins. Consensus ward linkage hierarchical clustering of 454 samples and 155 proteins identified 3 subtypes with the stability of the clustering increasing for k = 2 to k = 10.

    • Clustering of RPPA data: consensus NMF
      View Report | The most robust consensus NMF clustering of 454 samples using 155 proteins was identified for k = 6 clusters. We computed the clustering for k = 2 to k = 8 and used the cophenetic correlation coefficient to determine the best solution.

  • Other Analyses

    • Aggregate Analysis Features
      View Report | 537 samples and 615 features are included in this feature table. The figures below show which genomic pair events are co-occurring and which are mutually-exclusive.

  • Pathway Analyses

    • Association of mutation, copy number alteration, and subtype markers with pathways
      View Report | There are 21 genes with significant mutation (Q value <= 0.1) and 405 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 and copy number data
      View Report | There were 63 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNA expression data
      View Report | There were 70 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression and copy number data
      View Report | There were 42 significant pathways identified in this analysis.

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

  • Other Correlation Analyses

    • Correlation between copy number variation genes (focal events) and molecular subtypes
      View Report | Testing the association between copy number variation 30 focal events and 12 molecular subtypes across 528 patients, 126 significant findings detected with P value < 0.05 and 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 80 arm-level events and 12 molecular subtypes across 528 patients, 215 significant findings detected with P value < 0.05 and Q value < 0.25.

    • Correlation between gene mutation status and molecular subtypes
      View Report | Testing the association between mutation status of 29 genes and 12 molecular subtypes across 417 patients, 15 significant findings 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 = 316. Number of gene expression samples = 531. Number of methylation samples = 319.

    • Correlations between copy number and mRNA expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.17886, -0.0654, 0.0119, 0.0796, 0.1426, 0.2086, 0.27948, 0.36446, 0.4792, 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 781.1, 1496, 1929.3, 2345, 2766.5, 3231, 3736.7, 4289.8, 4973, respectively.

Methods & Data
Input

  • Summary Report Date = Wed Jan 21 16:47:09 2015

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