Analysis Overview
Thyroid Adenocarcinoma (Primary solid tumor)
21 April 2013 | analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C11J97R2
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 Thyroid Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013. Broad Institute of MIT and Harvard. doi:10.7908/C11J97R2
Overview
Introduction

This is an overview of Thyroid Adenocarcinoma analysis pipelines from Firehose run "21 April 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

- Copy number analysis (GISTIC2)
  View Report | There were 497 tumor samples used in this analysis: 18 significant arm-level results, 1 significant focal amplifications, and 32 significant focal deletions were found.

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

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

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

- 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 497 samples using the 35 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 5143 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 500 samples and 5143 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 RPPA data: consensus NMF
  View Report | The most robust consensus NMF clustering of 224 samples using 175 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.

- Clustering of RPPA data: consensus hierarchical
  View Report | 175 proteins were selected. Consensus average linkage hierarchical clustering of 224 samples and 175 proteins 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 461 samples using the 1500 most variable genes 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 mRNAseq gene expression: consensus hierarchical
  View Report | The 1500 most variable genes were selected. Consensus average linkage hierarchical clustering of 461 samples and 1500 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 precursor expression: consensus NMF
  View Report | We filtered the data to 150 most variable miRs. Consensus NMF clustering of 427 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 hierarchical
  View Report | We filtered the data to 150 most variable miRs. Consensus average linkage hierarchical clustering of 427 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.

- Correlation Analyses

- Correlation between copy number variations of arm-level result and selected clinical features
  View Report | Testing the association between copy number variation 42 arm-level results and 15 clinical features across 421 patients, 42 significant findings detected with Q value < 0.25.

- Correlation between copy number variation genes (focal) and selected clinical features
  View Report | Testing the association between copy number variation 26 arm-level results and 15 clinical features across 421 patients, 13 significant findings detected with Q value < 0.25.

- Correlation between gene methylation status and clinical features
  View Report | Testing the association between 17071 genes and 14 clinical features across 394 samples, statistically thresholded by Q value < 0.05, 12 clinical features related to at least one genes.

- Correlation between molecular cancer subtypes and selected clinical features
  View Report | Testing the association between subtypes identified by 8 different clustering approaches and 15 clinical features across 424 patients, 34 significant findings detected with P value < 0.05 and Q value < 0.25.

- Correlation between gene mutation status and selected clinical features
  View Report | Testing the association between mutation status of 33 genes and 15 clinical features across 289 patients, 5 significant findings detected with Q value < 0.25.

- Correlation between RPPA expression and clinical features
  View Report | Testing the association between 175 genes and 14 clinical features across 198 samples, statistically thresholded by Q value < 0.05, 10 clinical features related to at least one genes.

- Correlation between mRNAseq expression and clinical features
  View Report | Testing the association between 18001 genes and 14 clinical features across 397 samples, statistically thresholded by Q value < 0.05, 12 clinical features related to at least one genes.

- Correlation between miRseq expression and clinical features
  View Report | Testing the association between 517 genes and 14 clinical features across 373 samples, statistically thresholded by Q value < 0.05, 13 clinical features related to at least one genes.

- Correlations between copy number and mRNAseq expression
  View Report | The correlation coefficients in 10, 20, 30, 40, 50, 60, 70, 80, 90 percentiles are 431, 1192.8, 1781, 2101, 2410, 2750.4, 3127, 3612, 4270.6, respectively.

- Correlation between mRNA expression and DNA methylation
  View Report | The top 25 correlated methylation probes per gene are displayed. Total number of matched samples = 461. Number of gene expression samples = 461. Number of methylation samples = 461.

- Correlation between copy number variations of arm-level result and molecular subtypes
  View Report | Testing the association between copy number variation 45 arm-level results and 8 molecular subtypes across 497 patients, 102 significant findings detected with Q value < 0.25.

- Correlation between copy number variation genes and molecular subtypes
  View Report | Testing the association between copy number variation of 29 peak regions and 8 molecular subtypes across 497 patients, 53 significant findings detected with Q value < 0.25.

- Correlation between gene mutation status and molecular subtypes
  View Report | Testing the association between mutation status of 41 genes and 8 molecular subtypes across 323 patients, 20 significant findings detected with P value < 0.05 and Q value < 0.25.

- Pathway Analyses

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

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

- PARADIGM pathway analysis of mRNASeq expression and copy number data
  View Report | There were 39 significant pathways identified in this analysis.

Methods & Data
Input

- Summary Report Date = Sat May 25 14:04:28 2013

- Protection = FALSE

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