论文标题

调和多个连通性评分以重新利用药物

Reconciling Multiple Connectivity Scores for Drug Repurposing

论文作者

Samart, Kewalin, Tuyishime, Phoebe, Krishnan, Arjun, Ravi, Janani

论文摘要

最近几种药物重新利用方法的基础是,有效的药物会以最小的副作用逆转疾病分子“签名”的关键原则。该原则是由2006年的“连通性图”研究定义和普及的,该研究涉及疾病和药物诱导的基因表达谱之间的逆转关系,该研究由疾病 - 药物的“连通性评分”量化。在过去的15年中,鉴于参考药物谱的大量增长,有几项研究提出了在计算连通性评分方面的差异。但是,即使它们基于一组共同的概念和统计思想,这些变化也使用各种符号和术语不一致地表达了不一致。因此,我们介绍了多种疾病 - 药物相似性指标(ES,CSS,SUM,COSINE,XSUM,XSUM,XCOR,XSPE,XCOS,EWCOS)和连接得分(CS,RGES,NCS,WCS,WCS,TAU,TAU,CSS,EMUDRA)的系统核对。除了提供清晰度和更深入的见解外,这种连通性分数及其关系的连贯定义还提供了一种统一的方案,新方法可以采用,使计算药物开发社区能够轻松地比较和调查不同的方法。为了促进较新方法的持续透明整合,本文将作为实时文档(https://jravilab.github.io/connectivitivitive_scores)与github repository(https://github.com/github.com/jravilab/jravilab/connectivition_score)相结合。

The basis of several recent methods for drug repurposing is the key principle that an efficacious drug will reverse the disease molecular 'signature' with minimal side-effects. This principle was defined and popularized by the influential 'connectivity map' study in 2006 regarding reversal relationships between disease- and drug-induced gene expression profiles, quantified by a disease-drug 'connectivity score.' Over the past 15 years, several studies have proposed variations in calculating connectivity scores towards improving accuracy and robustness in light of massive growth in reference drug profiles. However, these variations have been formulated inconsistently using various notations and terminologies even though they are based on a common set of conceptual and statistical ideas. Therefore, we present a systematic reconciliation of multiple disease-drug similarity metrics (ES, css, Sum, Cosine, XSum, XCor, XSpe, XCos, EWCos) and connectivity scores (CS, RGES, NCS, WCS, Tau, CSS, EMUDRA) by defining them using consistent notation and terminology. In addition to providing clarity and deeper insights, this coherent definition of connectivity scores and their relationships provides a unified scheme that newer methods can adopt, enabling the computational drug-development community to compare and investigate different approaches easily. To facilitate the continuous and transparent integration of newer methods, this article will be available as a live document (https://jravilab.github.io/connectivity_scores) coupled with a GitHub repository (https://github.com/jravilab/connectivity_scores) that any researcher can build on and push changes to.

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