2022
DOI: 10.7554/elife.71880
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A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

Abstract: Pharmacologic perturbation projects, such as Connectivity Map (CMap) and Library of Integrated Network-based Cellular Signatures (LINCS), have produced many perturbed expression data, providing enormous opportunities for computational therapeutic discovery. However, there is no consensus on which methodologies and parameters are the most optimal to conduct such analysis. Aiming to fill this gap, new benchmarking standards were developed to quantitatively evaluate drug retrieval performance. Investigations of p… Show more

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Cited by 93 publications
(69 citation statements)
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“…In this communication, the performance of CancerOmicsNet is also compared to data-driven therapeutic discovery utilizing a popular concept of "signature reversion" that aims at molecules able to reverse disease-specific gene expression patterns [105]. Despite many examples of the successful application of GS-based methods reported to date, salient issues with this methodology remain unsolved [106].…”
Section: Discussionmentioning
confidence: 99%
“…In this communication, the performance of CancerOmicsNet is also compared to data-driven therapeutic discovery utilizing a popular concept of "signature reversion" that aims at molecules able to reverse disease-specific gene expression patterns [105]. Despite many examples of the successful application of GS-based methods reported to date, salient issues with this methodology remain unsolved [106].…”
Section: Discussionmentioning
confidence: 99%
“…Connective Map (CMap) ( Lamb et al, 2006 ) is a pharmacogenomics database based on the concept called “signature reversion” containing the expression profiles of cell lines before and after different drug treatments ( Li et al, 2016 ). We use the eXtreme Sum (XSum) and a compromising parameter (topN = 200) to match neutrophil-related genes in aSAH and compound signatures in CMap, which has been proven to show optimal drug retrieval performance ( Yang et al, 2022 ). Lower CMap scores generally correspond to higher reversal potency and greater potential for application.…”
Section: Methodsmentioning
confidence: 99%
“…Connectivity map (CMap) analysis was conducted to predict small-molecule compounds targeting immune microenvironment subtype 1 and subtype2 as previously reported (35). Briefly, a total of 1309 drug signatures were downloaded from the Connectivity Map database (CMap, https://clue.io/), the expression profiles of the top 150 up-regulated and 150 down-regulated were selected as the input data.…”
Section: Prediction Of Small-molecule Compoundsmentioning
confidence: 99%