Integrative Systems Biology Lab, Biological and Environmental Sciences and Engineering Division, Computer, Electrical and Mathematical Sciences and Engineering Division, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia; Division of Medical Genetics, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 USA.
Genomics. 2013 Oct;102(4):202-8. doi: 10.1016/j.ygeno.2013.07.010. Epub 2013 Jul 25.
Genetic interaction (GI) detection impacts the understanding of human disease and the ability to design personalized treatment. The mapping of every GI in most organisms is far from complete due to the combinatorial amount of gene deletions and knockdowns required. Computational techniques to predict new interactions based only on network topology have been developed in network science but never applied to GI networks. We show that topological prediction of GIs is possible with high precision and propose a graph dissimilarity index that is able to provide robust prediction in both dense and sparse networks. Computational prediction of GIs is a strong tool to aid high-throughput GI determination. The dissimilarity index we propose in this article is able to attain precise predictions that reduce the universe of candidate GIs to test in the lab.
遗传相互作用 (GI) 的检测影响着人们对人类疾病的理解和设计个性化治疗的能力。由于需要进行大量的基因缺失和敲低实验,大多数生物体中每一个 GI 的映射都远未完成。网络科学中已经开发出了仅基于网络拓扑结构来预测新相互作用的计算技术,但从未应用于 GI 网络。我们证明了基于拓扑结构预测 GI 是可行的,并且提出了一个图相似度指数,可以在密集和稀疏网络中提供稳健的预测。GI 的计算预测是辅助高通量 GI 确定的有力工具。本文提出的相似度指数能够进行精确预测,从而将候选 GI 的测试范围缩小到实验室中。
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