Association of mutation, copy number alteration, and subtype markers with pathways
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
22 February 2013 | analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1WW7FVB
Maintained by Spring Yingchun Liu (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Association of mutation, copy number alteration, and subtype markers with pathways. Broad Institute of MIT and Harvard. doi:10.7908/C1WW7FVB
Overview
Introduction

This pipeline maps genes, with mutation or copy number alteration AND this alteration is highly correlated with mRNA expression, to pathways curated in the KEGG and BIOCARTA databases. It identifies pathways significantly enriched with these genes. The pipeline also identifies pathways significantly enriched with marker genes of each expression subtype of cancer.

genes with mutation: identified by the Mutation_Significance pipeline

genes with copy number alteration: identified by the CopyNumber_Gistic2 pipeline

correlation between copy number and mRNA expression: identified by the Correlate_CopyNumber_vs_mRNA pipeline

marker genes and expression subtypes: identified by the mRNAConsensusClustering pipeline

Summary

There are 4 genes with significant mutation (Q value <= 0.1) and 341 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 0 for subtype 1. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

0 pathways significantly enriched with genes with copy number alteration or mutation.

0 pathways significantly enriched with marker genes of gene expression subtype 1

Results
The top five pathways enriched with genes with copy number alteration or mutation

Table 1. Get Full Table Top Pathways enriched with genes with copy number alteration or mutation. Nof Genes : No. of genes in this pathway. Nof CNV_Mut : No. of genes with copy number alteration or mutation in this pathway. Enrichment , P value and Q value : See Methods & Data below. CNV_Mut Genes in Pathway: genes with copy number alteration or mutation in this pathway.

Pathway | Nof Genes | Nof CNV_Mut | Enrichment | P value | Q value
--- | --- | --- | --- | --- | ---
KEGG_SPLICEOSOME | 126 | 9 | 2.3 | 0.0001 | 0.021
KEGG_P53_SIGNALING_PATHWAY | 69 | 7 | 2.6 | 0.0001 | 0.021
BIOCARTA_CTCF_PATHWAY | 23 | 4 | 3.4 | 0.0005 | 0.054
KEGG_RNA_DEGRADATION | 55 | 5 | 2.4 | 0.0021 | 0.17
KEGG_OXIDATIVE_PHOSPHORYLATION | 133 | 7 | 1.9 | 0.0028 | 0.18

List of CNV_Mut genes in this pathway

ACIN1,SLU7,SNRPG,SNW1,PLRG1,EIF4A3,THOC3,USP39,RBM25

List of CNV_Mut genes in this pathway

STEAP3,RPRM,PTEN,CDKN2A,PPM1D,RRM2,CCNG1

List of CNV_Mut genes in this pathway

RPS6KB1,PTEN,CDKN2A,CD79B

List of CNV_Mut genes in this pathway

CNOT8,CNOT6,C1D,PNPT1,PAPOLG

List of CNV_Mut genes in this pathway

COX5B,COX11,ATP6V0E1,ATP5H,ATP6V1D,ATP6V1C2,NDUFA3

The top five pathways enriched with marker genes of gene expression subtype 1

Table 2. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 1 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 1 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 1 in this pathway

Pathway | Nof Genes | Nof Marker | Enrichment | P value | Q value
--- | --- | --- | --- | --- | ---
BIOCARTA_RELA_PATHWAY | 16 | 0 | NaN | 1 | 1
BIOCARTA_NO1_PATHWAY | 31 | 0 | NaN | 1 | 1
BIOCARTA_CSK_PATHWAY | 24 | 0 | NaN | 1 | 1
BIOCARTA_AMI_PATHWAY | 20 | 0 | NaN | 1 | 1
BIOCARTA_ARAP_PATHWAY | 18 | 0 | NaN | 1 | 1

List of marker genes for gene expression subtype 1 in this pathway

List of marker genes for gene expression subtype 1 in this pathway

List of marker genes for gene expression subtype 1 in this pathway

List of marker genes for gene expression subtype 1 in this pathway

List of marker genes for gene expression subtype 1 in this pathway

Methods & Data
Enrichment

Let genes with copy number alteration or mutation be query genes. Let marker genes of specific identified subtypes be query genes. The Enrichment is calculated as:

- Enrichment = log2 (# of query genes in the pathway/# No of query genes) - log2 (# of genes in the pathway/# of human genes)

P value

The statistical signficance of the pathways that are enriched with genes with copy number alteration or mutation, and the pathways that are enriched with markers genes of specific identified subtypes is measured by P value.

- P value = Fisher exact P value

Q value

The Q value is for adjusting P value for multiple testing. A public available R package is used to calculate the Q value.

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

References
[1] Qi Zheng, GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis, Nucleic Acids Res. 36(issue suppl 2):W358-W363 (2008)
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