Glioblastoma Multiforme: HotNet pathway analysis of mutation and copy number data
(primary solid tumor cohort)
Maintained by Hailei Zhang (Broad Institute)
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 21 significant subnetworks identified in HotNet analysis.

Results
Significant subnetworks

HotNet identifies 21 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 21 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
--- | --- | --- | ---
IFNG(2),PDIA3(37),ERP27(38) | 3 | 0.0000 | 3
LAMA2(100),UTRN(99),DAG1(2) | 3 | 0.0005 | 2
SGCD(1),FLNC(242),MYOZ3(1) | 3 | 0.0005 | 2
CCNG1(2),CDKN2A(255),PSMC3(1),ZNF410(1),CDKN2C(238) | 5 | 0.0055 | 2
AVPR1A(1),HRH2(2),CHRM2(241) | 3 | 0.0000 | 1
AZI2(1),IRAK3(3),IRF5(241) | 3 | 0.0000 | 1
EPHA3(2),EPHB6(241),EPHA1(242) | 3 | 0.0000 | 1
RNF130(3),FGF18(1),FGFR3(29) | 3 | 0.0000 | 1
SMO(241),SHH(241),DLK1(1) | 3 | 0.0000 | 1
TNIP1(1),NVL(1),RPL5(18) | 3 | 0.0000 | 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 .

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 .

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] 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)
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