Quantitative protein profiling: determining lexotypes.

Abstract

The lexotype of a cell is defined as a set of quantitative characters of its informational macromolecular gene products, notably proteins, as observed under specified environmental conditions. This definition can be applied to cells in several ways that need to be distinguished. It can refer to the protein lexotype, to RNA lexotypes; to the steady-state lexotype, synthesis lexotype, functional protein lexotype; to the in situ lexotype and standard-environment lexotype. When used without qualification, the term lexotype may be applied to the standard-environment, steady-state protein lexotype. Some difficulties that currently limit our ability to determine lexotypes are assessed. Reasons are given why abnormal cellular states, such as states of disease, should often be characterizable by means of protein markers not themselves involved in the disease process and why one expects to find markers in tissues other than the one in which a certain pathological process may be anticipated to occur. There are three routes through which biological systems can produce secondary protein markers, namely through gene regulatory chains, through chromosomal gene linkage, and through "physiological linkage" of genes. The partly stable, partly shifting, yet defined relations between tissue lexotypes are considered. A number of potentially important fields of application of rigorous quantitative analyses of protein profiles are listed. One particular use of the technology is to investigate a hypothesis linking aging to degenerative diseases with late onset. According to this hypothesis, such diseases appear in later life as the cellular concentration of the active form of a protein passes a certain threshold in the course of the aging process.