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Systemic similarity analysis of compatibility drug-induced multiple pathway patterns _in vivo_

Abstract

A major challenge in post-genomic research is to understand how physiological and pathological phenotypes arise from the networks of expressed genes and to develop powerful tools for translating the information exchanged between gene and the organ system networks. Although different expression modules may contribute independently to different phenotypes, it is difficult to interpret microarray experimental results at the level of single gene associations. The global effects and response pathways of small molecules in cells have been investigated, but the quantitative details of the activation mechanisms of multiple pathways _in vivo_ are not well understood. Similar response networks indicate similar modes of action, and gene networks may appear to be similar despite differences in the behaviour of individual gene groups. Here we establish the method for assessing global effect spectra of the complex signaling forms using Global Similarity Index (GSI) in cosines vector included angle. Our approach provides quantitative multidimensional measures of genes expression profile based on drug-dependent phenotypic alteration _in vivo_. These results make a starting point for identifying relationships between GSI at the molecular level and a step toward phenotypic outcomes at a system level to predict action of unknown compounds and any combination therapy

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