Advances and perspectives in computational prediction of microbial gene essentiality

Abstract

The minimal subset of genes required for cellular growth, survival and viability of an organism are classified as essential genes. Knowledge of essential genes gives insight into the core structure and functioning of a cell. This might lead to more efficient antimicrobial drug discovery, to elucidation of the correlations between genotype and phenotype, and a better understanding of the minimal requirements for a (synthetic) cell. Traditionally, constructing a catalog of essential genes for a given microbe involved costly and time-consuming laboratory experiments. While experimental methods have produced abundant gene essentiality data for model organisms like Escherichia coli and Bacillus subtilis, the knowledge generated cannot automatically be extrapolated to predict essential genes in all bacteria. In addition, essential genes identified in the laboratory are by definition 'conditionally essential', as they are essential under the specified experimental conditions: these might not resemble conditions in the microorganisms' natural habitat(s). Also, large-scale experimental assaying for essential genes is not always feasible because of the time investment required to setup these assays. The ability to rapidly and precisely identify essential genes in silico is therefore important and has great potential for applications in medicine, biotechnology and basic biological research. Here, we review the advances made in the use of computational methods to predict microbial gene essentiality, perspectives for the future of these techniques and the possible practical applications of essential genes.