1. In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development.
- Author
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Ozerov IV, Lezhnina KV, Izumchenko E, Artemov AV, Medintsev S, Vanhaelen Q, Aliper A, Vijg J, Osipov AN, Labat I, West MD, Buzdin A, Cantor CR, Nikolsky Y, Borisov N, Irincheeva I, Khokhlovich E, Sidransky D, Camargo ML, and Zhavoronkov A
- Subjects
- Area Under Curve, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Female, Gene Expression Profiling, Humans, Models, Biological, Paclitaxel pharmacology, Paclitaxel therapeutic use, ROC Curve, Reproducibility of Results, Transcriptome genetics, Algorithms, Biomarkers metabolism, Computer Simulation
- 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., Competing Interests: Ivan V. Ozerov, Ksenia V. Lezhnina, Quentin Vanhaelen, Sergey Medintsev, Alexander Aliper, Artem V. Artemov, Anton Buzdin, Nikolay Borisov and Alex Zhavoronkov are affiliated with Insilico Medicine, Inc., a company engaged in aging research, which uses and provides both paid and free services using a variety of pathway activation scoring algorithms and hence may have competing financial interests.
- Published
- 2016
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