Dataset Information

Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing.

ABSTRACT:

Motivation

Transcriptome-based computational drug repurposing has attracted considerable interest by bringing about faster and more cost-effective drug discovery. Nevertheless, key limitations of the current drug connectivity-mapping paradigm have been long overlooked, including the lack of effective means to determine optimal query gene signatures.

Results

The novel approach Dr Insight implements a frame-breaking statistical model for the 'hand-shake' between disease and drug data. The genome-wide screening of concordantly expressed genes (CEGs) eliminates the need for subjective selection of query signatures, added to eliciting better proxy for potential disease-specific drug targets. Extensive comparisons on simulated and real cancer datasets have validated the superior performance of Dr Insight over several popular drug-repurposing methods to detect known cancer drugs and drug-target interactions. A proof-of-concept trial using the TCGA breast cancer dataset demonstrates the application of Dr Insight for a comprehensive analysis, from redirection of drug therapies, to a systematic construction of disease-specific drug-target networks.

Availability and implementation

Dr Insight R package is available at https://cran.r-project.org/web/packages/DrInsight/index.html.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Chan J

PROVIDER: S-EPMC6691331 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing.

Chan Jinyan J Wang Xuan X Turner Jacob A JA Baldwin Nicole E NE Gu Jinghua J

Bioinformatics (Oxford, England) 20190801 16

<h4>Motivation</h4>Transcriptome-based computational drug repurposing has attracted considerable interest by bringing about faster and more cost-effective drug discovery. Nevertheless, key limitations of the current drug connectivity-mapping paradigm have been long overlooked, including the lack of effective means to determine optimal query gene signatures.<h4>Results</h4>The novel approach Dr Insight implements a frame-breaking statistical model for the 'hand-shake' between disease and drug dat ...[more]

PMID: 30624606

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Project description:Cancer represents a significant global health and economic burden due to its high mortality rates. While effective in some instances, traditional chemotherapy often falls short of entirely eradicating various types of cancer. It can cause severe side effects due to harm to healthy cells. Two therapeutic approaches have risen to the forefront to address these limitations: metronomic chemotherapy (MCT) and drug repurposing. Metronomic chemotherapy is an innovative approach that breaks from traditional models. It involves the administration of chemotherapeutic regimens at lower doses, without long drug-free intervals that have previously been a hallmark of such treatments. This method offers a significant reduction in side effects and improved disease management. Simultaneously, drug repurposing has gained considerable attraction in cancer treatment. This approach involves utilizing existing drugs, initially developed for other therapeutic purposes, as potential cancer treatments. The application of known drugs in a new context accelerates the timeline from laboratory to patient due to pre-existing safety and dosage data. The intersection of these two strategies gives rise to a novel therapeutic approach named 'Metronomics.' This approach encapsulates the benefits of both MCT and drug repurposing, leading to reduced toxicity, potential for oral administration, improved patient quality of life, accelerated clinical implementation, and enhanced affordability. Numerous clinical studies have endorsed the efficacy of metronomic chemotherapy with tolerable side effects, underlining the potential of Metronomics in better cancer management, particularly in low- and middle-income countries. This review underscores the benefits and applications of metronomic chemotherapy and drug repurposing, specifically in the context of breast cancer, showcasing the promising results of pre-clinical and clinical studies. However, we acknowledge the necessity of additional clinical investigations to definitively establish the role of metronomic chemotherapy in conjunction with other treatments in comprehensive cancer management.

Dataset Information

Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing.

Motivation

Results

Availability and implementation

Supplementary information

Publications

Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing.

Similar Datasets

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