RT Journal Article
SR Electronic
T1 Inferring Genetic Interactions From Comparative Fitness Data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 137372
DO 10.1101/137372
A1 Kristina Crona
A1 Alex Gavryushkin
A1 Devin Greene
A1 Niko Beerenwinkel
YR 2017
UL http://biorxiv.org/content/early/2017/11/22/137372.abstract
AB Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax, the fungus Aspergillus niger, and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.