Gene network modeling via TopNet reveals functional dependencies between diverse tumor-critical mediator genes.

ABSTRACT: Malignant cell transformation and the underlying reprogramming of gene expression require the cooperation of multiple oncogenic mutations. This cooperation is reflected in the synergistic regulation of non-mutant downstream genes, so-called cooperation response genes (CRGs). CRGs affect diverse hallmark features of cancer cells and are not known to be functionally connected. However, they act as critical mediators of the cancer phenotype at an unexpectedly high frequency >50%, as indicated by genetic perturbations. Here, we demonstrate that CRGs function within a network of strong genetic interdependencies that are critical to the malignant state. Our network modeling methodology, TopNet, takes the approach of incorporating uncertainty in the underlying gene perturbation data and can ident

SUBMITTER: McMurray HR 

PROVIDER: S-EPMC8803128 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature