论文标题
具有GMM先验的癌症药物产生和敏感性预测的GMM的生成推荐系统
A generative recommender system with GMM prior for cancer drug generation and sensitivity prediction
论文作者
论文摘要
高通量药物筛查测定法的最新出现引发了机器学习方法的密集开发,包括预测癌细胞系对抗癌药物敏感性的模型,以及用于生成潜在药物候选物的方法。但是,尚未全面探索具有特定特性的化合物产生具有特定特性和同时建模其功效的概念。为了满足这一需求,我们提出了Vadeers,这是一种基于各种自动编码器的药物功效估算推荐系统。化合物的产生是由具有半监视的高斯混合模型(GMM)的新型自动编码器进行的。先验定义了在潜在空间中的聚类,其中簇与特定的药物特性相关联。此外,Vadeers配备了单元线自动编码器和灵敏度预测网络。该模型结合了抗癌药物的微笑字符串表示的数据,它们对蛋白激酶的抑制作用,细胞系生物学特征以及细胞系对药物敏感性的测量值。评估的Vadeers的变体在真实和预测的药物敏感性估计之间达到了高r = 0.87 Pearson的相关性。我们以这种方式训练GMM先验,使潜在空间中的簇通过其抑制作用对应于药物的预计聚类。我们表明,学到的潜在表示和新生成的数据点准确地反映了给定的聚类。总而言之,Vadeers提供了一种全面的药物和细胞系特性模型及其之间的关系,以及引导的新型化合物。
Recent emergence of high-throughput drug screening assays sparkled an intensive development of machine learning methods, including models for prediction of sensitivity of cancer cell lines to anti-cancer drugs, as well as methods for generation of potential drug candidates. However, a concept of generation of compounds with specific properties and simultaneous modeling of their efficacy against cancer cell lines has not been comprehensively explored. To address this need, we present VADEERS, a Variational Autoencoder-based Drug Efficacy Estimation Recommender System. The generation of compounds is performed by a novel variational autoencoder with a semi-supervised Gaussian Mixture Model (GMM) prior. The prior defines a clustering in the latent space, where the clusters are associated with specific drug properties. In addition, VADEERS is equipped with a cell line autoencoder and a sensitivity prediction network. The model combines data for SMILES string representations of anti-cancer drugs, their inhibition profiles against a panel of protein kinases, cell lines biological features and measurements of the sensitivity of the cell lines to the drugs. The evaluated variants of VADEERS achieve a high r=0.87 Pearson correlation between true and predicted drug sensitivity estimates. We train the GMM prior in such a way that the clusters in the latent space correspond to a pre-computed clustering of the drugs by their inhibitory profiles. We show that the learned latent representations and new generated data points accurately reflect the given clustering. In summary, VADEERS offers a comprehensive model of drugs and cell lines properties and relationships between them, as well as a guided generation of novel compounds.