In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development

Ivan V. Ozerov, Ksenia V. Lezhnina, Evgeny Izumchenko, Artem V. Artemov, Sergey Medintsev, Quentin Vanhaelen, Alexander Aliper, Jan Vijg, Andreyan N. Osipov, Ivan Labat, Michael D. West, Anton Buzdin, Charles R. Cantor, Yuri Nikolsky, Nikolay Borisov, Irina Irincheeva, Edward Khokhlovich, David Sidransky, Miguel Luiz Camargo, Alex Zhavoronkov

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Abstract

Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. However, modern pathway-based methods often fail to provide stable pathway signatures of a specific phenotype or reliable disease biomarkers. In the present study, we introduce the in silico Pathway Activation Network Decomposition Analysis (iPANDA) as a scalable robust method for biomarker identification using gene expression data. The iPANDA method combines precalculated gene coexpression data with gene importance factors based on the degree of differential gene expression and pathway topology decomposition for obtaining pathway activation scores. Using Microarray Analysis Quality Control (MAQC) data sets and pretreatment data on Taxol-based neoadjuvant breast cancer therapy from multiple sources, we demonstrate that iPANDA provides significant noise reduction in transcriptomic data and identifies highly robust sets of biologically relevant pathway signatures. We successfully apply iPANDA for stratifying breast cancer patients according to their sensitivity to neoadjuvant therapy.

Original languageEnglish (US)
Article number13427
JournalNature communications
Volume7
DOIs
StatePublished - Nov 16 2016

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Ozerov, I. V., Lezhnina, K. V., Izumchenko, E., Artemov, A. V., Medintsev, S., Vanhaelen, Q., Aliper, A., Vijg, J., Osipov, A. N., Labat, I., West, M. D., Buzdin, A., Cantor, C. R., Nikolsky, Y., Borisov, N., Irincheeva, I., Khokhlovich, E., Sidransky, D., Camargo, M. L., & Zhavoronkov, A. (2016). In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development. Nature communications, 7, [13427]. https://doi.org/10.1038/ncomms13427