HotNet pathway analysis of mutation and copy number data
Bladder Urothelial Carcinoma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
Maintained by Hailei Zhang (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): HotNet pathway analysis of mutation and copy number data. Broad Institute of MIT and Harvard. doi:10.7908/C1VD6WM2
Overview
Introduction

HotNet is an algrithom for finding altered subnetworks in a large protein-protein interaction network conatinning a significant number of mutations and copy number alterations (CNAs).

Summary

There were 18 significant subnetworks identified in HotNet analysis.

Results
Significant subnetworks

HotNet identifies 18 altered subnetworks based on the matched somatic mutation and copy number alterations data. Table 1 showes the top 10 significant subnetworks.

Table 1.  Get Full Table Top 10 out of 18 subnetworks in ranked by p value. The last column of RepeatTimes shows how many times the subnetwork was picked up in differenct delta values.

Network No.ofgenes p-value RepeatTimes
DOCK3(11),PSEN1(1),APH1A(12) 3 0 1
EIF4G3(18),EIF4G2(6),EIF4A2(15) 3 0 1
HNRNPU(1),ERBB4(13),YAP1(11) 3 0 1
HRH4(1),GNA15(6),OPRD1(17) 3 0 1
KLK1(13),KNG1(15),CTSS(12) 3 0 1
LAMB3(1),LAMA3(4),COL7A1(13) 3 0 1
UBE4B(17),UBE4A(10),GZMB(1) 3 0 1
WEE1(5),FBXW11(1),BRD8(1) 3 0 1
ERBB2(16),PIK3C2A(6),MATK(6),GRB7(14) 4 0 1
F8(2),C4BPA(1),PROS1(3),F5(1) 4 0 1
Methods & Data
Input

Somatic mutation data from Mutsig pipeline, copy number alterations derived from GISTIC pipeline and influence matrix derived from Human Protein Reference Database (HPRD) provided by HotNet website ##REF##2.

HotNet Method

HotNet is an algorithm for de novo identification of significantly altered subnetworks.First, it formulates an influence measure between pairs of genes in the network using a diffusion process defined on the graph. Second, it identifies subnetworks using either a combinatorial model or an enhanced influence model. Finally, it derives a two-stage multiple hypothesis test that mitigates the testing of a large number of hypotheses in subnetwork discovery ##REF##1.

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.

References
[1] HotNet
[2] F. Vandin, E. Upfal, and B.J. Raphael., Algorithms for Detecting Significantly Mutated Pathways in Cancer, Journal of Computational Biology 18(3):507-22 (2011)