Analysis Overview
Pancreatic Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1RV0MM1
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 Pancreatic Adenocarcinoma (Primary solid tumor cohort) - 17 October 2014. Broad Institute of MIT and Harvard. doi:10.7908/C1RV0MM1
Overview
Introduction

This is an overview of Pancreatic Adenocarcinoma 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 41 tumor samples in this analysis. The Benjamini-Hochberg-corrected p-value for enrichment of the APOBEC mutation signature in 2 samples is <=0.05. Out of these, 2 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 15951 mutations identified by MuTect and 597 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 184 tumor samples used in this analysis: 21 significant arm-level results, 25 significant focal amplifications, and 38 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 133 patients, no significant finding 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 63 focal events and 12 clinical features across 132 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 events and 12 clinical features across 132 patients, no significant finding detected with Q value < 0.25.

    • Correlation between gene methylation status and clinical features
      View Report | Testing the association between 20446 genes and 12 clinical features across 111 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 2 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 138 genes and 12 clinical features across 35 patients, no significant finding detected with Q value < 0.25.

    • Correlation between miRseq expression and clinical features
      View Report | Testing the association between 507 miRs and 12 clinical features across 130 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 1 clinical feature related to at least one miRs.

    • Correlation between mRNAseq expression and clinical features
      View Report | Testing the association between 18475 genes and 12 clinical features across 130 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 3 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 81 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, no clinical feature related to at least one variables.

    • Correlation between RPPA expression and clinical features
      View Report | Testing the association between 193 genes and 12 clinical features across 86 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 1 clinical feature 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 184 samples using the 63 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 184 samples using the 63 copy number focal regions 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.

    • Clustering of Methylation: consensus NMF
      View Report | The 1607 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 146 samples and 1607 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 174 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 174 samples and 647 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 | Median absolute deviation (MAD) was used to select 126 most variable miRs. Consensus ward linkage hierarchical clustering of 178 samples and 126 miRs identified 3 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 178 samples and 150 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 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 178 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 178 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 193 most variable proteins. Consensus ward linkage hierarchical clustering of 106 samples and 193 proteins identified 5 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 106 samples using 193 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 | 184 samples and 1917 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

    • PARADIGM pathway analysis of mRNASeq expression and copy number data
      View Report | There were 45 significant pathways identified in this analysis.

    • PARADIGM pathway analysis of mRNASeq expression data
      View Report | There were 46 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 63 focal events and 10 molecular subtypes across 184 patients, 91 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 79 arm-level events and 10 molecular subtypes across 184 patients, 49 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 148 genes and 10 molecular subtypes across 41 patients, no 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 = 140. Number of gene expression samples = 178. Number of methylation samples = 146.

    • Correlations between copy number and mRNAseq expression
      View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are 843, 1821.4, 2423.6, 2982, 3530, 4088, 4676, 5306.6, 6049.8, respectively.

Methods & Data
Input

  • Summary Report Date = Wed Jan 21 17:22:34 2015

  • Protection = FALSE

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