Network signatures based on gene pair expression ratios improve classification and the analysis of muscle-invasive urothelial cancer

Ricardo De Matos Simoes, Constantine Mitsiades, Kathleen Williamson, Frank Emmert-Streib

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Urothelial cancer (UC) is highly recurrent and can progress from non-invasive (NMIUC) to a more aggressive muscle-invasive (MIUC) subtype that invades the muscle tissue layer of the bladder. We present a proof of principle study that network-based features of gene pairs can be used to improve classifier performance and the functional analysis of urothelial cancer gene expression data. In the first step of our procedure each individual sample of a UC gene expression dataset is inflated by gene pair expression ratios that are defined based on a given network structure. In the second step an elastic net feature selection procedure for network-based signatures is applied to discriminate between NMIUC and MIUC samples. We performed a repeated random subsampling cross validation in three independent datasets. The network signatures were characterized by a functional enrichment analysis and studied for the enrichment of known cancer genes. We observed that the network-based gene signatures from meta collections of proteinprotein interaction (PPI) databases such as CPDB and the PPI databases HPRD and BioGrid improved the classification performance compared to single gene based signatures. The network based signatures that were derived from PPI databases showed a prominent enrichment of cancer genes (e.g., TP53, TRIM27 and HNRNPA2Bl). We provide a novel integrative approach for large-scale gene expression analysis for the identification and development of novel diagnostical targets in bladder cancer. Further, our method allowed to link cancer gene associations to network-based expression signatures that are not observed in gene-based expression signatures.

Original languageEnglish
Title of host publicationProceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages1216-1223
Number of pages8
ISBN (Print)9781467367981
DOIs
Publication statusPublished - 16 Dec 2015
EventIEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015 - Washington, United States
Duration: 09 Nov 201512 Nov 2015

Conference

ConferenceIEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
CountryUnited States
CityWashington
Period09/11/201512/11/2015

Keywords

  • data feature space inflation
  • feature selection
  • gene pair expression ratio
  • muscle-invasive
  • non muscleinvasive
  • Urothelial cancer

ASJC Scopus subject areas

  • Software
  • Artificial Intelligence
  • Health Informatics
  • Biomedical Engineering

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