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 and Alex Zhavoronkov ()
Additional contact information
Ivan V. Ozerov: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Ksenia V. Lezhnina: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Evgeny Izumchenko: The Johns Hopkins University, School of Medicine, Head and Neck Cancer Research
Artem V. Artemov: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Sergey Medintsev: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Quentin Vanhaelen: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Alexander Aliper: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Jan Vijg: Albert Einstein College of Medicine
Andreyan N. Osipov: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Ivan Labat: BioTime, Inc.
Michael D. West: BioTime, Inc.
Anton Buzdin: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Charles R. Cantor: Boston University
Yuri Nikolsky: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Nikolay Borisov: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Irina Irincheeva: Nutrition and Metabolic Health group, Nestlé Institute of Health Sciences
Edward Khokhlovich: Novartis Institutes for BioMedical Research
David Sidransky: The Johns Hopkins University, School of Medicine, Head and Neck Cancer Research
Miguel Luiz Camargo: Novartis Institutes for BioMedical Research
Alex Zhavoronkov: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13427

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