Analysis Overview
Ovarian Serous Cystadenocarcinoma (Primary solid tumor)
16 April 2014 | analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1CR5S1X
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 Ovarian Serous Cystadenocarcinoma (Primary solid tumor cohort) - 16 April 2014. Broad Institute of MIT and Harvard. doi:10.7908/C1CR5S1X
Overview
Introduction

This is an overview of Ovarian Serous Cystadenocarcinoma analysis pipelines from Firehose run "16 April 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

- CHASM 1.0.5 (Cancer-Specific High-throughput Annotation of Somatic Mutations)
  View Report | There are 90 mutations identified by MuTect and 1 mutations with significant functional impact at BHFDR <= 0.25.

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

- Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result)
  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 569 tumor samples used in this analysis: 32 significant arm-level results, 32 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 14 different clustering approaches and 6 clinical features across 578 patients, 3 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 68 focal events and 6 clinical features across 562 patients, 9 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 80 arm-level events and 6 clinical features across 562 patients, 15 significant findings detected with Q value < 0.25.

- Correlation between gene methylation status and clinical features
  View Report | Testing the association between 14047 genes and 6 clinical features across 574 samples, statistically thresholded by Q value < 0.05, 4 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 3 genes and 3 clinical features across 316 patients, no significant finding detected with Q value < 0.25.

- Correlation between miR expression and clinical features
  View Report | Testing the association between 817 miRs and 6 clinical features across 560 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one miRs.

- Correlation between miRseq expression and clinical features
  View Report | Testing the association between 415 miRs and 5 clinical features across 453 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one miRs.

- Correlation between mRNA expression and clinical features
  View Report | Testing the association between 18632 genes and 6 clinical features across 562 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.

- Correlation between mRNAseq expression and clinical features
  View Report | Testing the association between 18555 genes and 3 clinical features across 261 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one genes.

- Correlation between RPPA expression and clinical features
  View Report | Testing the association between 165 genes and 5 clinical features across 407 samples, statistically thresholded by Q value < 0.05, 3 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 569 samples using the 68 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 569 samples using the 68 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 2419 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 582 samples and 2419 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 miR expression: consensus hierarchical
  View Report | We filtered the data to 150 most variable miRs. Consensus average linkage hierarchical clustering of 568 samples and 150 miRs identified 6 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 miR expression: consensus NMF
  View Report | We filtered the data to 150 most variable miRs. Consensus NMF clustering of 568 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 mature expression: consensus hierarchical
  View Report | We filtered the data to 189 most variable miRs. Consensus average linkage hierarchical clustering of 453 samples and 189 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 189 most variable miRs. Consensus NMF clustering of 453 samples and 189 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 453 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 453 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 | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 569 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 mRNA expression: consensus NMF
  View Report | The most robust consensus NMF clustering of 569 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 | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 261 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 261 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 | 165 proteins were selected. Consensus average linkage hierarchical clustering of 412 samples and 165 proteins 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 RPPA data: consensus NMF
  View Report | The most robust consensus NMF clustering of 412 samples using 165 proteins 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.

- Other Analyses

- Identification of putative miR direct targets
  View Report | This pipeline use a relevance network approach to infer putative miR:mRNA regulatory connections. All miR:mRNA pairs that have correlations < -0.3 and have predicted interactions in three sequence prediction databases (Miranda, Pictar, Targetscan) define the final network.

- Pathway Analyses

- Association of mutation, copy number alteration, and subtype markers with pathways
  View Report | There are 2 genes with significant mutation (Q value <= 0.1) and 231 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 :

- HotNet pathway analysis of mutation and copy number data
  View Report

- PARADIGM pathway analysis of mRNA expression and copy number data
  View Report | There were 77 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNA expression data
  View Report | There were 65 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNASeq expression and copy number data
  View Report | There were 31 significant pathways identified in this analysis.

- PARADIGM pathway analysis of mRNASeq expression data
  View Report | There were 40 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 68 focal events and 14 molecular subtypes across 569 patients, 74 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 14 molecular subtypes across 569 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 3 genes and 14 molecular subtypes across 316 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 = 261. Number of gene expression samples = 261. Number of methylation samples = 582.

- Correlations between copy number and miR expression
  View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are -0.0361, -0.01828, 0.00444, 0.01676, 0.0393, 0.07706, 0.13056, 0.23136, 0.35344, respectively.

- Correlations between copy number and mRNA expression
  View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are 0.0155, 0.0651, 0.1219, 0.2006, 0.2915, 0.3837, 0.4583, 0.531, 0.6006, 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 1088, 1799, 2426, 3130, 3902, 4703, 5448, 6127, 6795, respectively.

Methods & Data
Input

- Summary Report Date = Sat May 10 11:24:48 2014

- Protection = FALSE

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