The goal of computational biology in the early twenty-first century is to l
ink the various genome sequencing projects to a high-throughput effort in c
omplete structural and functional annotation of whole genomes or biological
pathways. If is, in fact, a logical extension of the genome effort to syst
ematically elaborate DNA (deoxyribonucleic acid) sequences into full three-
dimensional structures through to functional analysis of cellular networks.
The first level of the biological hierarchy is comparative analysis of the
rapidly emerging genomic data at the sequence level. However, knowing only
the sequence of DNA does not always tell us about the structure or functio
n of the genes, nor does it fell us about the combined action of their prot
ein products, which is the essence of higher order biological function. Com
plete annotation will include the determination of structure and function o
f proteins, and a move from analysis of these individual macromolecules to
their complex interactions that make up the processes of cellular decisions
. This paper represents an effort by a research community to define the har
d computational biology problems of the future, to define what mixture of b
asic research directions and practical algorithmic approaches will be requi
red to achieve our goals, and to outline the directions that will likely be
taken in the postgenomic era.