Analysis Overview
Bladder Urothelial Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1HT2N9N
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Analysis Overview for Bladder Urothelial Carcinoma (Primary solid tumor cohort) - 02 April 2015. Broad Institute of MIT and Harvard. doi:10.7908/C1HT2N9N
Overview
Introduction

This is an overview of Bladder Urothelial Carcinoma analysis pipelines from Firehose run "02 April 2015".

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 395 tumor samples in this analysis. The Benjamini-Hochberg-corrected p-value for enrichment of the APOBEC mutation signature in 347 samples is <=0.05. Out of these, 329 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 75496 mutations identified by MuTect and 2241 mutations with significant functional impact at BHFDR <= 0.25.

    • LowPass Copy number analysis (GISTIC2)
      View Report | There were 112 tumor samples used in this analysis: 22 significant arm-level results, 20 significant focal amplifications, and 13 significant focal deletions were found.

    • 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 408 tumor samples used in this analysis: 29 significant arm-level results, 33 significant focal amplifications, and 36 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 10 different clustering approaches and 12 clinical features across 393 patients, 52 significant findings detected with P value < 0.05 and Q value < 0.25.

    • Correlation between APOBEC groups and selected clinical features
      View Report | Testing the association between APOBEC groups identified by 2 different apobec score and 12 clinical features across 376 patients, 5 significant findings detected with Q value < 0.25.

    • Correlation between APOBEC signature variables and clinical features
      View Report | Testing the association between 3 variables and 12 clinical features across 376 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 3 clinical features related to at least one variables.

    • Correlation between copy number variation genes (focal events) and selected clinical features
      View Report | Testing the association between copy number variation 69 focal events and 12 clinical features across 389 patients, 24 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 82 arm-level events and 12 clinical features across 389 patients, 14 significant findings detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 19914 genes and 12 clinical features across 393 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 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 118 genes and 12 clinical features across 376 patients, no significant finding detected with Q value < 0.25.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 572 miRs and 12 clinical features across 391 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one miRs.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 18215 genes and 12 clinical features across 389 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

    • Correlation between mutation rate and clinical features
      View Report | Testing the association between 2 variables and 13 clinical features across 376 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 179 genes and 12 clinical features across 127 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 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 408 samples using the 69 copy number focal regions 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 copy number data by peak region with threshold value: consensus NMF
      View Report | The most robust consensus NMF clustering of 408 samples using the 69 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 10451 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 412 samples and 10451 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 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 398 samples and 647 miRs identified 6 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 398 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 143 most variable miRs. Consensus ward linkage hierarchical clustering of 409 samples and 143 miRs identified 5 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 409 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 | Median absolute deviation (MAD) was used to select 1500 most variable genes. Consensus ward linkage hierarchical clustering of 408 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 408 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 179 most variable proteins. Consensus ward linkage hierarchical clustering of 127 samples and 179 proteins identified 4 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 127 samples using 179 proteins 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.

  • Other Analyses

    • Aggregate Analysis Features
      View Report | 411 samples and 721 features are included in this feature table. The figures below show which genomic pair events are co-occurring and which are mutually-exclusive.

    • Identification of putative miR direct targets by sequencing data
      View Report | The CLR algorithm was applied on 806 miRs and 18215 mRNAs across 405 samples. After 2 filtering steps, the number of 126 miR:genes pairs were detected.

  • Pathway Analyses

    • GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in BLCA-TP
      View Report | basic data info

    • PARADIGM pathway analysis of mRNASeq expression and copy number data
      View Report | There were 63 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression data
      View Report | There were 63 significant pathways identified in this analysis.

    • Significant over-representaion of pathway genesets for a given gene list
      View Report | For a given gene list, a hypergeometric test was tried to find significant overlapping canonical pathway gene sets. In terms of FDR adjusted p.values, top 5 significant overlapping gene sets are listed as below.

  • Other Correlation Analyses

    • Correlation between copy number variation genes (focal events) and molecular subtypes
      View Report | Testing the association between copy number variation 69 focal events and 10 molecular subtypes across 408 patients, 328 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 82 arm-level events and 10 molecular subtypes across 408 patients, 281 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 118 genes and 10 molecular subtypes across 395 patients, 34 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 = 408. Number of gene expression samples = 408. Number of methylation samples = 412.

    • Correlations between APOBEC_MutLoad_MinEstimate and mRNAseq expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.088, -0.0567, -0.0344, -0.01474, 0.0046, 0.0235, 0.0446, 0.069, 0.10216, 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 931, 1483, 2002.9, 2537.2, 3153.5, 3818, 4501, 5155, 5877.7, respectively.

Methods & Data
Input

  • Summary Report Date = Sat Aug 15 11:36:26 2015

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