Some 60 years ago, the promise of molecular biology held that if we knew and understood the function of the molecules that comprise cells, then we could understand cells and their functions. Although this was true in principle (and in practice in a few cases), the sheer number of molecules made it very difficult to comprehend so many simultaneous functions. The simultaneous measurement of the majority of these molecules became possible over the last 10–15 years through the development of many ingenious technologies. As a result, we now have a growing number of data sets that give us the composition of particular cells and organisms under certain conditions. The chemical interactions between many of these components are now known and this knowledge gives rise to reconstructed biochemical reaction networks on a genome-scale that underlie various cellular functions. Thus, enter (molecular) systems biology.

Systems biology is not necessarily focused on the components themselves, but on the nature of the links that connect them and on the functional states of the biochemical networks that result from the collection of all such links. These functional states of networks correspond to observable physiological or homeostatic states. Completing the relationship between all the chemical components of a cell, with their genetic bases, and its physiological functions is the promise of (molecular) systems biology. This undertaking represents the de facto construction of a mechanistic genotype– phenotype relationship.

The Genotype–Phenotype Relationship

The concept Through breeding experiments, Gregor Mendel discovered that there are discrete quanta of information passed from one generation to the next that determine the form and function of an organism. These quanta, or packets, of information are now generally referred to as genes. The collection of all the genes and the particular version of them found in a genome of an individual organism is referred to as its genotype. The form and function of an organism is referred to as its phenotype. How the phenotype is related to the genotype represents the fundamental relationship of biology.