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OncoFinder, a family of new methods for the analysis of complex intracellular signaling networks and its applications to biomedicine, drug discovery and practical anticancer therapy of glioblastoma

Alex Zhavoronkov (1,3,4), Nicolas Borisov (1), Alexander Aliper (1,3), Ksenia Lezhnina (1,3), Denis Shepelin(1,3), Michael Korzinkin (1,3), Artem Artemov (1,3), Qinsong Zhu (1), Anton Buzdin (1,2,3,4)


Analysis of the complete transcriptomes is complicated by the problems with understanding of the overall functional features basing on the observed large-scale gene expression profiles. We propose a new biomathematical method, OncoFinder, which for the first time enables performing both quantitative and qualitative analysis of the intracellular signaling pathway activation (SPA). This method is universal and may be used for the analysis of any physiological, stress, malignancy and other user-defined conditions at the molecular level. In contrast to other techniques, OncoFinder utilizes an algorithm that distinguishes the activator/repressor role of every gene product in each pathway. This unique feature enables to quantitatively characterize activation of each signaling pathway in a given biosample. We show that the relative importance of each gene product in a pathway can be assessed using kinetic models for “low-level” protein interactions. OncoFinder technique showed a strong potential to neutralize differences between the experimental data obtained using NGS and microarray hybridization, using most of the commercially available platforms. This approach also allowed us to characterize new SPA signatures as the better markers of cancer progression compared to the individual gene products. OncoFinder also enables to correlate SPA with the success of anticancer therapy of the individual patients. To facilitate using OncoFinder platform by the biomedical society, we created a software package available freely for the academic community. Some aspects of the enclosing technology were published recently: (Buzdin, http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00055/abstract); (Zhavoronkov, http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00049/abstract ); Spirin et al, Leukemia 2014; Aliper et al, Aging 2015; Makarev et al, Aging 2014; Borisov et al, Oncotarget 2014; Lezhnina et al, Oncotarget 2014; Aliper et al, Oncotarget 2014;.Zhu et al, Human Genome Variation 2015. The authors enthusiastically support building international scientific collaborations and partnerships.

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