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整合机器学习和生物信息学方法,以鉴定与卵巢癌化疗耐药相关的遗传相互作用。

Integration and interplay of machine learning and bioinformatics approach to identify genetic interaction related to ovarian cancer chemoresistance.

机构信息

School of Electronics Engineering and Computer Science, Peking University, 100871, Beijing, China.

Department of Biomedical Engineering, Duke University, 27708, Durham, United States.

出版信息

Brief Bioinform. 2021 Nov 5;22(6). doi: 10.1093/bib/bbab100.

Abstract

Although chemotherapy is the first-line treatment for ovarian cancer (OCa) patients, chemoresistance (CR) decreases their progression-free survival. This paper investigates the genetic interaction (GI) related to OCa-CR. To decrease the complexity of establishing gene networks, individual signature genes related to OCa-CR are identified using a gradient boosting decision tree algorithm. Additionally, the genetic interaction coefficient (GIC) is proposed to measure the correlation of two signature genes quantitatively and explain their joint influence on OCa-CR. Gene pair that possesses high GIC is identified as signature pair. A total of 24 signature gene pairs are selected that include 10 individual signature genes and the influence of signature gene pairs on OCa-CR is explored. Finally, a signature gene pair-based prediction of OCa-CR is identified. The area under curve (AUC) is a widely used performance measure for machine learning prediction. The AUC of signature gene pair reaches 0.9658, whereas the AUC of individual signature gene-based prediction is 0.6823 only. The identified signature gene pairs not only build an efficient GI network of OCa-CR but also provide an interesting way for OCa-CR prediction. This improvement shows that our proposed method is a useful tool to investigate GI related to OCa-CR.

摘要

虽然化疗是卵巢癌 (OCa) 患者的一线治疗方法,但化疗耐药性 (CR) 降低了他们的无进展生存期。本文研究了与 OCa-CR 相关的遗传相互作用 (GI)。为了降低建立基因网络的复杂性,使用梯度提升决策树算法识别与 OCa-CR 相关的个体特征基因。此外,还提出了遗传相互作用系数 (GIC),以定量衡量两个特征基因的相关性,并解释它们对 OCa-CR 的共同影响。具有高 GIC 的基因对被确定为特征对。总共选择了 24 对特征基因,其中包括 10 个个体特征基因,并探讨了特征基因对 OCa-CR 的影响。最后,确定了基于特征基因对的 OCa-CR 预测。曲线下面积 (AUC) 是机器学习预测中广泛使用的性能度量。特征基因对的 AUC 达到 0.9658,而基于个体特征基因的预测的 AUC 仅为 0.6823。所鉴定的特征基因对不仅构建了 OCa-CR 的有效 GI 网络,而且为 OCa-CR 预测提供了一种有趣的方法。这种改进表明,我们提出的方法是研究与 OCa-CR 相关的 GI 的有用工具。

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