Table of Contents
ISRN Bioinformatics
Volume 2012 (2012), Article ID 381023, 11 pages
http://dx.doi.org/10.5402/2012/381023
Research Article

A Robust Topology-Based Algorithm for Gene Expression Profiling

1Department of Physics, University of Houston, Houston, TX 77204, USA
2Department of Physics, Richard Stockton College of New Jersey, Pomona, NJ 08240, USA

Received 3 August 2012; Accepted 30 August 2012

Academic Editors: B. Haubold and K. Yura

Copyright © 2012 Lars Seemann et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Early and accurate diagnoses of cancer can significantly improve the design of personalized therapy and enhance the success of therapeutic interventions. Histopathological approaches, which rely on microscopic examinations of malignant tissue, are not conducive to timely diagnoses. High throughput genomics offers a possible new classification of cancer subtypes. Unfortunately, most clustering algorithms have not been proven sufficiently robust. We propose a novel approach that relies on the use of statistical invariants and persistent homology, one of the most exciting recent developments in topology. It identifies a sufficient but compact set of genes for the analysis as well as a core group of tightly correlated patient samples for each subtype. Partitioning occurs hierarchically and allows for the identification of genetically similar subtypes. We analyzed the gene expression profiles of 202 tumors of the brain cancer glioblastoma multiforme (GBM) given at the Cancer Genome Atlas (TCGA) site. We identify core patient groups associated with the classical, mesenchymal, and proneural subtypes of GBM. In our analysis, the neural subtype consists of several small groups rather than a single component. A subtype prediction model is introduced which partitions tumors in a manner consistent with clustering algorithms but requires the genetic signature of only 59 genes.