학술논문
ASTER: A Method to Predict Clinically Relevant Synthetic Lethal Genetic Interactions
Document Type
Periodical
Author
Source
IEEE Journal of Biomedical and Health Informatics IEEE J. Biomed. Health Inform. Biomedical and Health Informatics, IEEE Journal of. 28(3):1785-1796 Mar, 2024
Subject
Language
ISSN
2168-2194
2168-2208
2168-2208
Abstract
A Synthetic Lethal (SL) interaction is a functional relationship between two genes or functional entities where the loss of either entity is viable but the loss of both is lethal. Such pairs can be used to develop targeted anticancer therapies with fewer side effects and reduced overtreatment. However, finding clinically relevant SL interactions remains challenging. Leveraging unified gene expression data of both disease-free and cancerous samples, we design a new technique based on statistical hypothesis testing, called ASTER, to identify SL pairs. We empirically find that the patterns of mutually exclusivity ASTER finds using genomic and transcriptomic data provides a strong signal of synthetic lethality. For large-scale multiple hypothesis testing, we develop an extension called ASTER++ that can utilize additional input gene features within the hypothesis testing framework. Our computational and functional experiments demonstrate the efficacy of ASTER in identifying SL pairs with potential therapeutic benefits.