Association of mutation, copy number alteration, and subtype markers with pathways
Kidney Renal Clear Cell Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
Maintained by Spring Yingchun Liu (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Association of mutation, copy number alteration, and subtype markers with pathways. Broad Institute of MIT and Harvard. doi:10.7908/C1NV9H97
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 27 genes with significant mutation (Q value <= 0.1) and 405 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 852 for subtype 1, 852 for subtype 2, 852 for subtype 3, 852 for subtype 4, 852 for subtype 5, 852 for subtype 6. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

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

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

0 pathways significantly enriched with marker genes of gene expression subtype 2

0 pathways significantly enriched with marker genes of gene expression subtype 3

0 pathways significantly enriched with marker genes of gene expression subtype 4

0 pathways significantly enriched with marker genes of gene expression subtype 5

0 pathways significantly enriched with marker genes of gene expression subtype 6

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_PATHWAYS_IN_CANCER 325 21 1.7 0 0.001
KEGG_ENDOMETRIAL_CANCER 52 8 2.9 0 0.0015
BIOCARTA_IGF1MTOR_PATHWAY 20 5 3.6 0 0.0033
KEGG_NOTCH_SIGNALING_PATHWAY 47 7 2.9 0 0.0033
BIOCARTA_CHEMICAL_PATHWAY 22 5 3.5 0.0001 0.0043
List of CNV_Mut genes in this pathway

PIK3CA,PIK3CD,DVL1,MITF,MLH1,PTEN,TP53,TFG,GSK3B,PTCH1,WNT2,EGFR,FGFR3,ARNT,MET,HDAC2,MTOR,CASP9,TPR,EGLN1,VHL

List of CNV_Mut genes in this pathway

MLH1,PTEN,CASP9,PIK3CA,EGFR,PIK3CD,TP53,GSK3B

List of CNV_Mut genes in this pathway

PTEN,GSK3B,EIF2S1,PIK3CA,MTOR

List of CNV_Mut genes in this pathway

NUMB,DLL1,SNW1,DVL1,NCSTN,NOTCH2,HDAC2

List of CNV_Mut genes in this pathway

TP53,ATM,CASP9,EIF2S1,PARP1

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

The top five pathways enriched with marker genes of gene expression subtype 2

Table 3.  Get Full Table Top Pathways enriched with marker genes of gene expression subtype 2 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 2 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 2 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 2 in this pathway

List of marker genes for gene expression subtype 2 in this pathway

List of marker genes for gene expression subtype 2 in this pathway

List of marker genes for gene expression subtype 2 in this pathway

List of marker genes for gene expression subtype 2 in this pathway

The top five pathways enriched with marker genes of gene expression subtype 3

Table 4.  Get Full Table Top Pathways enriched with marker genes of gene expression subtype 3 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 3 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 3 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 3 in this pathway

List of marker genes for gene expression subtype 3 in this pathway

List of marker genes for gene expression subtype 3 in this pathway

List of marker genes for gene expression subtype 3 in this pathway

List of marker genes for gene expression subtype 3 in this pathway

The top five pathways enriched with marker genes of gene expression subtype 4

Table 5.  Get Full Table Top Pathways enriched with marker genes of gene expression subtype 4 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 4 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 4 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 4 in this pathway

List of marker genes for gene expression subtype 4 in this pathway

List of marker genes for gene expression subtype 4 in this pathway

List of marker genes for gene expression subtype 4 in this pathway

List of marker genes for gene expression subtype 4 in this pathway

The top five pathways enriched with marker genes of gene expression subtype 5

Table 6.  Get Full Table Top Pathways enriched with marker genes of gene expression subtype 5 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 5 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 5 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 5 in this pathway

List of marker genes for gene expression subtype 5 in this pathway

List of marker genes for gene expression subtype 5 in this pathway

List of marker genes for gene expression subtype 5 in this pathway

List of marker genes for gene expression subtype 5 in this pathway

The top five pathways enriched with marker genes of gene expression subtype 6

Table 7.  Get Full Table Top Pathways enriched with marker genes of gene expression subtype 6 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 6 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 6 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 6 in this pathway

List of marker genes for gene expression subtype 6 in this pathway

List of marker genes for gene expression subtype 6 in this pathway

List of marker genes for gene expression subtype 6 in this pathway

List of marker genes for gene expression subtype 6 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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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)