Gene prioritization based on random walks with restarts and absorbing states, to define gene sets regulating drug pharmacodynamics from single-cell analyses.

ABSTRACT: Prioritizing genes for their role in drug sensitivity, is an important step in understanding drugs mechanisms of action and discovering new molecular targets for co-treatment. To formalize this problem, we consider two sets of genes X and P respectively composing the gene signature of cell sensitivity at the drug IC50 and the genes involved in its mechanism of action, as well as a protein interaction network (PPIN) containing the products of X and P as nodes. We introduce Genetrank, a method to prioritize the genes in X for their likelihood to regulate the genes in P. Genetrank uses asymmetric random walks with restarts, absorbing states, and a suitable renormalization scheme. Using novel so-called saturation indices, we show that the conjunction of absorbing states and renormalization yie

SUBMITTER: Sales de Queiroz A 

PROVIDER: S-EPMC9639845 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature