School of Statistics, University of Minnesota, Minneapolis, Minnesota, USA.
Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA.
Stat Med. 2022 Sep 10;41(20):4034-4056. doi: 10.1002/sim.9491. Epub 2022 Jun 18.
In precision medicine, the ultimate goal is to recommend the most effective treatment to an individual patient based on patient-specific molecular and clinical profiles, possibly high-dimensional. To advance cancer treatment, large-scale screenings of cancer cell lines against chemical compounds have been performed to help better understand the relationship between genomic features and drug response; existing machine learning approaches use exclusively supervised learning, including penalized regression and recommender systems. However, it would be more efficient to apply reinforcement learning to sequentially learn as data accrue, including selecting the most promising therapy for a patient given individual molecular and clinical features and then collecting and learning from the corresponding data. In this article, we propose a novel personalized ranking system called Proximal Policy Optimization Ranking (PPORank), which ranks the drugs based on their predicted effects per cell line (or patient) in the framework of deep reinforcement learning (DRL). Modeled as a Markov decision process, the proposed method learns to recommend the most suitable drugs sequentially and continuously over time. As a proof-of-concept, we conduct experiments on two large-scale cancer cell line data sets in addition to simulated data. The results demonstrate that the proposed DRL-based PPORank outperforms the state-of-the-art competitors based on supervised learning. Taken together, we conclude that novel methods in the framework of DRL have great potential for precision medicine and should be further studied.
在精准医学中,最终目标是以患者特定的分子和临床特征(可能是高维的)为基础,为个体患者推荐最有效的治疗方法。为了推进癌症治疗,已经对癌细胞系进行了大规模的化合物筛选,以帮助更好地理解基因组特征与药物反应之间的关系;现有的机器学习方法仅使用有监督学习,包括惩罚回归和推荐系统。然而,随着数据的积累,应用强化学习来顺序学习将更加高效,包括根据个体分子和临床特征为患者选择最有前途的疗法,然后收集和学习相应的数据。在本文中,我们提出了一种名为近策略优化排序(PPORank)的新的个性化排序系统,该系统在深度强化学习(DRL)框架内根据每个细胞系(或患者)的预测效果对药物进行排序。该模型被建模为一个马尔可夫决策过程,所提出的方法学会了随着时间的推移顺序和连续地推荐最合适的药物。作为概念验证,我们在两个大型癌症细胞系数据集以及模拟数据上进行了实验。结果表明,基于强化学习的 DRL 提出的方法优于基于监督学习的最先进的竞争对手。综上所述,我们得出结论,DRL 框架中的新方法在精准医学方面具有巨大的潜力,应该进一步研究。