SYNPRED: prediction of drug combination effects in cancer using different synergy metrics and ensemble learning

Author:

Preto António J12ORCID,Matos-Filipe Pedro1ORCID,Mourão Joana3ORCID,Moreira Irina S43ORCID

Affiliation:

1. Center for Neuroscience and Cell Biology , University of Coimbra, 3004-504 Coimbra, Portugal

2. PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra , Casa Costa Alemão, 3030-789 Coimbra, Portugal

3. CNC—Center for Neuroscience and Cell Biology, CIBB—Center for Innovative Biomedicine and Biotechnology , 3004-504 Coimbra, Portugal

4. Department of Life Sciences , University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal

Abstract

Abstract Background In cancer research, high-throughput screening technologies produce large amounts of multiomics data from different populations and cell types. However, analysis of such data encounters difficulties due to disease heterogeneity, further exacerbated by human biological complexity and genomic variability. The specific profile of cancer as a disease (or, more realistically, a set of diseases) urges the development of approaches that maximize the effect while minimizing the dosage of drugs. Now is the time to redefine the approach to drug discovery, bringing an artificial intelligence (AI)–powered informational view that integrates the relevant scientific fields and explores new territories. Results Here, we show SYNPRED, an interdisciplinary approach that leverages specifically designed ensembles of AI algorithms, as well as links omics and biophysical traits to predict anticancer drug synergy. It uses 5 reference models (Bliss, Highest Single Agent, Loewe, Zero Interaction Potency, and Combination Sensitivity Score), which, coupled with AI algorithms, allowed us to attain the ones with the best predictive performance and pinpoint the most appropriate reference model for synergy prediction, often overlooked in similar studies. By using an independent test set, SYNPRED exhibits state-of-the-art performance metrics either in the classification (accuracy, 0.85; precision, 0.91; recall, 0.90; area under the receiver operating characteristic, 0.80; and F1-score, 0.91) or in the regression models, mainly when using the Combination Sensitivity Score synergy reference model (root mean square error, 11.07; mean squared error, 122.61; Pearson, 0.86; mean absolute error, 7.43; Spearman, 0.87). Moreover, data interpretability was achieved by deploying the most current and robust feature importance approaches. A simple web-based application was constructed, allowing easy access by nonexpert researchers. Conclusions The performance of SYNPRED rivals that of the existing methods that tackle the same problem, yielding unbiased results trained with one of the most comprehensive datasets available (NCI ALMANAC). The leveraging of different reference models allowed deeper insights into which of them can be more appropriately used for synergy prediction. The Combination Sensitivity Score clearly stood out with improved performance among the full scope of surveyed approaches and synergy reference models. Furthermore, SYNPRED takes a particular focus on data interpretability, which has been in the spotlight lately when using the most advanced AI techniques.

Funder

European Regional Development Fund

Fundação para a Ciência e a Tecnologia

Publisher

Oxford University Press (OUP)

Subject

Computer Science Applications,Health Informatics

Reference89 articles.

1. A view on drug resistance in cancer;Vasan;Nature,2019

2. Polytherapy and targeted cancer drug resistance;Chatterjee;Trends Cancer,2019

3. Single-omics to interactomics: how can ligand-induced perturbations modulate single-cell phenotypes?;Piochi,2022

4. An introduction to terminology and methodology of chemical synergy—perspectives from across disciplines;Roell;Front Pharmacol,2017

Cited by 22 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3