Approaches to systems biology. Four methods to study single-cell gene expression, cell motility, antibody reactivity, and respiratory metabolism

To understand how complex systems, such as cells, function, comprehensive Measurements of their constituent parts must be made. This can be achieved by combining methods that are each optimized to measure specific parts of the system. Four such methods,each covering a different area, are presented: Transcript profiling of one cell type extracted from a complex tissue containing several cell types; observation and recording of cell motility; measurement of antibody reactivities using microarrays; and invivo measurement of free and bound NADH in mitochondria.

Detailed statistical analysis of the data from such measurements allows models of the system to be developed and tested. For each of the methods, such analysis and modelling approaches have beenapplied and are presented: Differentially regulated genes are identified and classified according to function; cell-specfic motility models are developed that can distinguish between different surfaces; a method for selecting repertoires of antigens thatseparate mice based on their response to treatment is developed; and the observed concentrations of free and bound NADH is used to build and test a basic model of respiratory metabolism.

The significance of each of the methods is exemplified by specificresults and insights into the systems analyzed. But also, it is discussed how the methods relate to high-throughput biology in general, and how they (and similar methods) may be combined to rationalize the structure and kinetics of complex networks ofinteracting parts in terms of function.