Cellular decision-making bias: the missing ingredient in cell functional diversity

Abstract

Cell functional diversity is a significant determinant on how biological processes unfold. Most accounts of diversity involve a search for sequence or expression differences. Perhaps there are more subtle mechanisms at work. Using the metaphor of information processing and decision-making might provide a clearer view of these subtleties. Understanding adaptive and transformative processes (such as cellular reprogramming) as a series of simple decisions allows us to use a technique called cellular signal detection theory (cellular SDT) to detect potential bias in mechanisms that favor one outcome over another. We can apply method of detecting cellular reprogramming bias to cellular reprogramming and other complex molecular processes. To demonstrate scope of this method, we will critically examine differences between cell phenotypes reprogrammed to muscle fiber and neuron phenotypes. In cases where the signature of phenotypic bias is cryptic, signatures of genomic bias (pre-existing and induced) may provide an alternative. The examination of these alternates will be explored using data from a series of fibroblast cell lines before cellular reprogramming (pre-existing) and differences between fractions of cellular RNA for individual genes after drug treatment (induced). In conclusion, the usefulness and limitations of this method and associated analogies will be discussed.