Improving Anticancer Drug Selection and Prioritization via Neural Learning to Rank

• Published in: Journal of chemical information and modeling Vol. 64; no. 10; pp. 4071 - 4088
• Main Authors: Dey, Vishal, Ning, Xia
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.05.2024
• Subjects: Antineoplastic Agents - pharmacology; Cancer; Cell Line, Tumor; Chemical Information; Clustering; Drug Discovery - methods; Drugs; Humans; Neural Networks, Computer; Ranking; Representations; State-of-the-art reviews
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/acs.jcim.3c01060

Personalized cancer treatment requires a thorough understanding of complex interactions between drugs and cancer cell lines in varying genetic and molecular contexts. To address this, high-throughput screening has been used to generate large-scale drug response data, facilitating data-driven computational models. Such models can capture complex drug–cell line interactions across various contexts in a fully data-driven manner. However, accurately prioritizing the most effective drugs for each cell line still remains a significant challenge. To address this, we developed multiple neural ranking approaches that leverage large-scale drug response data across multiple cell lines from diverse cancer types. Unlike existing approaches that primarily utilize regression and classification techniques for drug response prediction, we formulated the objective of drug selection and prioritization as a drug ranking problem. In this work, we proposed multiple pairwise and listwise neural ranking methods that learn latent representations of drugs and cell lines and then use those representations to score drugs in each cell line via a learnable scoring function. Specifically, we developed neural pairwise and listwise ranking methods, Pair-PushC and List-One on top of the existing methods, pLETORg and ListNet, respectively. Additionally, we proposed a novel listwise ranking method, List-All, that focuses on all the effective drugs instead of the top effective drug, unlike List-One. We also provide an exhaustive empirical evaluation with state-of-the-art regression and ranking baselines on large-scale data sets across multiple experimental settings. Our results demonstrate that our proposed ranking methods mostly outperform the best baselines with significant improvements of as much as 25.6% in terms of selecting truly effective drugs within the top 20 predicted drugs (i.e., hit@20) across 50% test cell lines. Furthermore, our analyses suggest that the learned latent spaces from our proposed methods demonstrate informative clustering structures and capture relevant underlying biological features. Moreover, our comprehensive evaluation provides a thorough and objective comparison of the performance of different methods (including our proposed ones).