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Abstract Synthetic lethality, the combination of two mutated genes which results in cell death, has been greatly investigated due to its therapeutic potential in cancer. Despite the common practice of experimentally detecting synthetic lethality, here we extend a computational framework that employs co-occurrence of gene mutations to infer synthetic lethality by incorporating pathways. Pathways aggregate the mutated genes into a functional unit and give power to uncover relationships containing genes of low mutation frequency e.g. in pediatric cancer, which otherwise would not be observed by testing individual gene pairs. Our proposed framework is an alternative avenue to a more focused synthetic lethality search by exploiting mutation data 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B027.
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