Learning signaling networks from combinatorial perturbations by exploiting siRNA off-target effects.

ABSTRACT:

Motivation

Perturbation experiments constitute the central means to study cellular networks. Several confounding factors complicate computational modeling of signaling networks from this data. First, the technique of RNA interference (RNAi), designed and commonly used to knock-down specific genes, suffers from off-target effects. As a result, each experiment is a combinatorial perturbation of multiple genes. Second, the perturbations propagate along unknown connections in the signaling network. Once the signal is blocked by perturbation, proteins downstream of the targeted proteins also become inactivated. Finally, all perturbed network members, either directly targeted by the experiment, or by propagation in the network, contribute to the observed effect, either in a positive or n

SUBMITTER: Tiuryn J 

PROVIDER: S-EPMC6612802 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature