ABSTRACT

I. INTRODUCTION Technology and scale are themes that define all things ‘‘omic’’ and the emerging offspring of the genomics revolution variously called proteomics, functional genomics, or systems biology can be attributed an overall aim: As only a fraction of gene functions can be inferred from primary gene sequences, we need to develop strategies to define gene function that are not conducted at the level of a classical gene-by-gene approach but that aim at characterizing the totality of genes or large subsets thereof. The question then is, by what approaches do we meaningfully ascribe function to genes and, more so, address the problems that genomics has traditionally sought to address, such as establishing common and unique traits to determine phylogenic and evolutionary relationships among organisms? In the broadest and most ambitious sense, those of us working at the frontiers beyond the analysis of DNA sequence data hope that our efforts will result in a deeper appreciation of the biochemical organization of living cells and the molecular schemes that all living things share as well as those things that make individual cells and organisms unique. In this review we describe a general strategy that goes directly to the heart of this problem: physically mapping biochemical pathways in living cells.