Back to the future: The human protein index (HPI) and the agenda for post-proteomic biology

The effort to produce an index of all human proteins (the human protein ind ex, or HPI) began twenty years ago, before the initiation of the human geno me program. Because DNA sequencing technology is inherently simpler and mor e scalable than protein analytical technology, and because the finiteness o f genomes invited a spirit of rapid conquest, the notion of genome sequenci ng has displaced that of protein databases in the minds of most molecular b iologists for the last decade. However, now that the human genome sequence is nearing completion, a major realignment is under way that brings protein s back to the center of biological thinking. Using an influx of new and imp roved protein technologies - from mass spectrometry to re-engineered two-di mensional (2-D) gel systems, the original objectives of the HPI have been e xpanded and the time frame for its execution radically shortened. Several a dditional large scale technology efforts flowing from the HPI are also desc ribed.