ABSTRACT

A central philosophy of systems biology, and even biology in general, is to study and understand complex systems/networks through perturbations. Each perturbation can be viewed as a genotypic alteration, resulting in the loss or gain of one or more reactions. A common way to deduce the function of a gene is by studying a knock-out mutant with the corresponding gene deleted. The biological unit of deletion is a gene—in laboratory experiments, genes can be silenced, knocked out or their corresponding enzyme inhibited by some chemical agent. There is no way to selectively remove a reaction from a cell per se. Beyond single gene/reaction deletions, it is also possible to perform deletions of more than one gene/reaction. Among such combinatorial deletions, of special interest are synthetic lethals, which are sets of genes, where only the simultaneous removal of the all genes in the set abrogates growth.