Beerenwinkel Niko, Eriksson Nicholas, Sturmfels Bernd
Department of Mathematics, University of California, Berkeley, CA 94720, USA.
J Theor Biol. 2006 Sep 21;242(2):409-20. doi: 10.1016/j.jtbi.2006.03.013. Epub 2006 May 2.
We consider the directed evolution of a population after an intervention that has significantly altered the underlying fitness landscape. We model the space of genotypes as a distributive lattice; the fitness landscape is a real-valued function on that lattice. The risk of escape from intervention, i.e., the probability that the population develops an escape mutant before extinction, is encoded in the risk polynomial. Tools from algebraic combinatorics are applied to compute the risk polynomial in terms of the fitness landscape. In an application to the development of drug resistance in HIV, we study the risk of viral escape from treatment with the protease inhibitors ritonavir and indinavir.
我们考虑在显著改变潜在适应度景观的干预之后种群的定向进化。我们将基因型空间建模为一个分配格；适应度景观是该格上的实值函数。干预逃逸风险，即种群在灭绝前产生逃逸突变体的概率，编码在风险多项式中。应用代数组合学的工具根据适应度景观来计算风险多项式。在一个关于HIV耐药性发展的应用中，我们研究了病毒从使用蛋白酶抑制剂利托那韦和茚地那韦治疗中逃逸的风险。
