Beyond synthetic lethality in large-scale metabolic and regulatory network models via genetic minimal intervention set.

ABSTRACT:

Motivation

The integration of genome-scale metabolic and regulatory networks has received significant interest in cancer systems biology. However, the identification of lethal genetic interventions in these integrated models remains challenging due to the combinatorial explosion of potential solutions. To address this, we developed the genetic Minimal Cut Set (gMCS) framework, which computes synthetic lethal interactions-minimal sets of gene knockouts that are lethal for cellular proliferation- in genome-scale metabolic networks with signed directed acyclic regulatory pathways. Here, we present a novel formulation to calculate genetic Minimal Intervention Sets, gMISs, which incorporate both gene knockouts and knock-ins.

Results

With our gMIS approach, we assessed the landsca

SUBMITTER: Barrena N 

PROVIDER: S-EPMC12784249 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature