Robust selection algorithm (RSA) for multi-omic biomarker discovery; integration with functional network analysis to identify miRNA regulated pathways in multiple cancers

Vasudha Sehgal, Elena G. Seviour, Tyler J. Moss, Gordon Mills, Robert Azencott, Prahlad T. Ram

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) play a crucial role in the maintenance of cellular homeostasis by regulating the expression of their target genes. As such, the dysregulation of miRNA expression has been frequently linked to cancer. With rapidly accumulating molecular data linked to patient outcome, the need for identification of robust multi-omic molecular markers is critical in order to provide clinical impact. While previous bioinformatic tools have been developed to identify potential biomarkers in cancer, these methods do not allow for rapid classification of oncogenes versus tumor suppressors taking into account robust differential expression, cutoffs, p-values and non-normality of the data. Here, we propose a methodology, Robust Selection Algorithm (RSA) that addresses these important problems in big data omics analysis. The robustness of the survival analysis is ensured by identification of optimal cutoff values of omics expression, strengthened by p-value computed through intensive random resampling taking into account any non-normality in the data and integration into multi-omic functional networks. Here we have analyzed pan-cancer miRNA patient data to identify functional pathways involved in cancer progression that are associated with selected miRNA identified by RSA. Our approach demonstrates the way in which existing survival analysis techniques can be integrated with a functional network analysis framework to efficiently identify promising biomarkers and novel therapeutic candidates across diseases.

Original languageEnglish (US)
Article numbere0140072
JournalPLoS One
Volume10
Issue number10
DOIs
StatePublished - Oct 27 2015
Externally publishedYes

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Biomarkers
Electric network analysis
MicroRNAs
microRNA
biomarkers
neoplasms
Survival Analysis
Neoplasms
Bioelectric potentials
Bioinformatics
Tumor Biomarkers
Computational Biology
Oncogenes
oncogenes
Tumors
Homeostasis
bioinformatics
Genes
Maintenance
homeostasis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Robust selection algorithm (RSA) for multi-omic biomarker discovery; integration with functional network analysis to identify miRNA regulated pathways in multiple cancers. / Sehgal, Vasudha; Seviour, Elena G.; Moss, Tyler J.; Mills, Gordon; Azencott, Robert; Ram, Prahlad T.

In: PLoS One, Vol. 10, No. 10, e0140072, 27.10.2015.

Research output: Contribution to journalArticle

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