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A Hybrid Interpolation Weighted Collaborative Filtering Method for Anti-cancer Drug Response Prediction

机译:混合插值加权协同滤波方法在抗癌药物反应预测中的应用

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摘要

Individualized therapies ask for the most effective regimen for each patient, while the patients' response may differ from each other. However, it is impossible to clinically evaluate each patient's response due to the large population. Human cell lines have harbored most of the same genetic changes found in patients' tumors, thus are widely used to help understand initial responses of drugs. Based on the more credible assumption that similar cell lines and similar drugs exhibit similar responses, we formulated drug response prediction as a recommender system problem, and then adopted a hybrid interpolation weighted collaborative filtering (HIWCF) method to predict anti-cancer drug responses of cell lines by incorporating cell line similarity and drug similarity shown from gene expression profiles, drug chemical structure as well as drug response similarity. Specifically, we estimated the baseline based on the available responses and shrunk the similarity score for each cell line pair as well as each drug pair. The similarity scores were then shrunk and weighted by the correlation coefficients drawn from the know response between each pair. Before used to find the K most similar neighbors for further prediction, they went through the case amplification strategy to emphasize high similarity and neglect low similarity. In the last step for prediction, cell line-oriented and drug-oriented collaborative filtering models were carried out, and the average of predicted values from both models was used as the final predicted sensitivity. Through 10-fold cross validation, this approach was shown to reach accurate and reproducible outcome for those missing drug sensitivities. We also found that the drug response similarity between cell lines or drugs may play important role in the prediction. Finally, we discussed the biological outcomes based on the newly predicted response values in GDSC dataset.
机译:个体化治疗要求每个患者最有效的治疗方案,而患者的反应可能彼此不同。但是,由于人口众多,不可能在临床上评估每个患者的反应。人类细胞系具有与患者肿瘤中发现的大多数相同的遗传变化,因此被广泛用于帮助理解药物的初始反应。基于更可靠的假设,即相似的细胞系和相似的药物表现出相似的反应,我们将药物反应预测公式化为推荐系统问题,然后采用混合插值加权协同过滤(HIWCF)方法预测细胞的抗癌药物反应通过整合从基因表达图谱,药物化学结构以及药物反应相似性中显示的细胞系相似性和药物相似性来构建细胞系。具体来说,我们根据可用的响应估算基线,并缩小每个细胞系对以及每个药物对的相似性评分。然后将相似度分数缩小,并根据从每对之间的已知响应得出的相关系数进行加权。在用来找到K个最相似的邻居进行进一步预测之前,他们经历了案例放大策略来强调高相似度而忽略了低相似度。在预测的最后一步中,进行了面向细胞系和面向药物的协同过滤模型,并将这两个模型的预测值的平均值用作最终的预测灵敏度。通过10倍交叉验证,对于缺少药物敏感性的患者,该方法已显示出准确且可重复的结果。我们还发现,细胞系或药物之间的药物反应相似性可能在预测中起重要作用。最后,我们根据GDSC数据集中新预测的响应值讨论了生物学结果。

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