Small genome sequencing and annotations are leading to the definition of me
tabolic genotypes in an increasing number of organisms. Proteomics is begin
ning to give insights into the use of the metabolic genotype under given gr
owth conditions. These data sets give the basis for systemically studying t
he genotype-phenotype relationship. Methods of systems science need to be e
mployed to analyze, interpret, and predict this complex relationship. These
endeavors will lead to the development of a new field, tentatively named p
henomics. This article illustrates how the metabolic characteristics of ann
otated small genomes can be analyzed using flux balance analysis (FBA). A g
eneral algorithm for the formulation of in silico metabolic genotypes is de
scribed. Illustrative analyses of the in silico Escherichia coli K-12 metab
olic genotypes are used to show how FBA can be used to study the capabiliti
es of this strain.