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Front Genet. 2014 Mar 25;5:55. doi: 10.3389/fgene.2014.00055. eCollection 2014.

Oncofinder, a new method for the analysis of intracellular signaling pathway activation using transcriptomic data.

Author information

1
Pathway Pharmaceuticals, Limited Wan Chai, Hong Kong, Hong Kong ; D. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology Moscow, Russia ; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Moscow, Russia ; Biological and Medical Physics, Moscow Institute of Physics and Technology Dolgoprudny, Russia.
2
Pathway Pharmaceuticals, Limited Wan Chai, Hong Kong, Hong Kong ; D. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology Moscow, Russia ; Biological and Medical Physics, Moscow Institute of Physics and Technology Dolgoprudny, Russia.
3
Pathway Pharmaceuticals, Limited Wan Chai, Hong Kong, Hong Kong ; Burnasyan Federal Medical Biophysical Center Moscow, Russia.
4
Burnasyan Federal Medical Biophysical Center Moscow, Russia.
5
Pathway Pharmaceuticals, Limited Wan Chai, Hong Kong, Hong Kong ; Biological and Medical Physics, Moscow Institute of Physics and Technology Dolgoprudny, Russia ; Burnasyan Federal Medical Biophysical Center Moscow, Russia.

Abstract

We propose a new biomathematical method, OncoFinder, for 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 perturbed conditions at the molecular level. In contrast to the other existing techniques for aggregation and generalization of the gene expression data for individual samples, we suggest to distinguish the positive/activator and negative/repressor role of every gene product in each pathway. We show that the relative importance of each gene product in a pathway can be assessed using kinetic models for "low-level" protein interactions. Although the importance factors for the pathway members cannot be so far established for most of the signaling pathways due to the lack of the required experimental data, we showed that ignoring these factors can be sometimes acceptable and that the simplified formula for SPA evaluation may be applied for many cases. We hope that due to its universal applicability, the method OncoFinder will be widely used by the researcher community.

KEYWORDS:

expression level profiling; microchip transcriptome investigation; mitogenic signaling pathways; signalome profiling; stochastic robustness analysis; targeted anti-cancer drugs

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