REVIEW Integrating Genome-Scale Data for Gene Essentiality Prediction by Seth B. Roberts , Aure ´lien J. Mazurie, and Gregory A. Buck* Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia 23284-2030, USA (phone: þ 1-804-828-3897; fax: þ 1-804-828-1397; e-mail: gabuck@vcu.edu) 1. Introduction. – 1.1. Definition of Gene Essentiality and Caveats . Gene essentiality refers to the phenotypic effects of disrupting the function of a specific gene. A gene is said to be essential if such a disruption results in cell death, i.e. , inability to complete a certain number of cell divisions. In contrast, disruption of nonessential genes may slow growth or have other phenotypic effects, but the cells remain viable. This seemingly straightforward definition is subject to a number of caveats. First, essentiality is always defined relative to a specific set of environmental conditions. For example, the fruR gene of Escherichia coli is essential during growth on glycerol- supplemented minimal medium, but it is not essential during growth on glucose- supplemented minimal medium [1]. In fact, evidence suggests that a substantial fraction of E. coli genes may be regarded as either essential or nonessential, depending on the specific set of conditions [2]. Because the ability to predict gene essentiality is generally evaluated relative to experimental results using rich culture medium [3][4], we here define essential genes as those required for viability during growth under these conditions. Second, as recently highlighted by Gerdes et al. [5], there is a distinction between genes essential for survival and genes essential for fitness. When genes are experimentally disrupted to assess their essentiality, the resulting mutant cells may be propagated as clones (no competition during outgrowth) or as mixed populations (competition during outgrowth). One expects that the set of genes identified as essential in the absence of competition should be reduced compared to the set identified in competitive conditions. No competition implies that only genes perform- ing core living processes are required. This expectation has indeed been borne out experimentally [4][6]. In the experimental findings reviewed below, essentiality prediction is almost always done for the yeast Saccharomyces cerevisiae. Again, because these predictions are evaluated relative to available experimental results based on clonal propagation [3][7], (essential) in this work generally refers to essential for survival. These criteria for essential genes are potentially problematic, but necessary if essentiality predictions are to be verified using available experimental results. One concern is the possibility that genes required for viability on rich culture medium are not required in wild-type conditions. This would imply the existence of biological CHEMISTRY & BIODIVERSITY – Vol. 4 (2007) 2618 # 2007 Verlag Helvetica Chimica Acta AG, Zürich