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

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.

Figure 1

Values of pathway activation strength (APAS) that were calculated using the 98 random trials, each having random log-normally distributed weighting factors w_n, vs. non-perturbed PAS for the different SPs, calculated using OncoFinder method. The pathway information was extracted from the SABiosciences database. Primary data are shown on the Supplementary dataset 3. For the perturbed values (APAS), both average values (points at the plot) and standard deviation bars are shown.