Science
A gene expression signature is simply a representation of a biological state in the form of a pattern unique to that circumstance. Underlying the concept is the realization that virtually any biological condition, whether a developmental state, a cellular response to extracellular ligands, or a pathological state, is reflected in changes in gene expression.
While no one single gene would have the power to define the biological state, the ability to measure and identify patterns of gene expression provides an opportunity to develop these signatures reflecting biological phenotypes. In a sense, the expression signature becomes a surrogate representation of the biological phenotype.
To generate a signature, the gene expression levels in tumor cells representing the two biological states of interest (i.e., resistant and sensitive, or recurrent or indolent) are measured on a microarray. In order to maximize the discriminating power of the signature, tumor cell lines, which exhibit extremes of the characteristic of interest (i.e., resistance and sensitivity) are selected as a training set.
The gene expression data are normalized, and standard binary regression models combined with singular value decompositions (SVD's) and stochastic regularization using Bayesian analysis are used to identify a pattern of genes that are differentially expressed between the two states.
The power of the CancerGuide expression signature is two-fold:
First, the enormous complexity of the expression data that can be sampled provides the opportunity to identify patterns of expression that reflect very subtle distinctions in biology. The main limitation is the capacity to define the biological state of interest, whether through the generation of distinct experimental states or by taking advantage of existing biological conditions that can be used as the training opportunity.
Second, the CancerGuide expression signature is portable in the sense that it can be assayed in varied contexts. That is, a CancerGuide expression signature developed in a cell culture context can be measured in a tumor or a histological section.
As such, the CancerGuide expression signature provides the capacity to link otherwise heterologous systems. A cell culture phenotype such as pathway activation is difficult to represent in a diverse sample such as a tumor.