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An integrative network-based approach for drug target indication expansion
by
Zhu, Cheng
, Klinger, Katherine
, Han, Yingnan
, Wang, Clarence
, Rajpal, Deepak K.
in
Algorithms
/ Alliances
/ Analysis
/ Biology and Life Sciences
/ Computer and Information Sciences
/ Disease
/ Drug discovery
/ Genes
/ Indication
/ Interleukin 1
/ Interleukin 12
/ Interleukin 23
/ Machine learning
/ Medicine and Health Sciences
/ Methods
/ Performance evaluation
/ Physical Sciences
/ Physiology
/ Research and Analysis Methods
/ Target recognition
/ Therapeutic targets
2021
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An integrative network-based approach for drug target indication expansion
by
Zhu, Cheng
, Klinger, Katherine
, Han, Yingnan
, Wang, Clarence
, Rajpal, Deepak K.
in
Algorithms
/ Alliances
/ Analysis
/ Biology and Life Sciences
/ Computer and Information Sciences
/ Disease
/ Drug discovery
/ Genes
/ Indication
/ Interleukin 1
/ Interleukin 12
/ Interleukin 23
/ Machine learning
/ Medicine and Health Sciences
/ Methods
/ Performance evaluation
/ Physical Sciences
/ Physiology
/ Research and Analysis Methods
/ Target recognition
/ Therapeutic targets
2021
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Do you wish to request the book?
An integrative network-based approach for drug target indication expansion
by
Zhu, Cheng
, Klinger, Katherine
, Han, Yingnan
, Wang, Clarence
, Rajpal, Deepak K.
in
Algorithms
/ Alliances
/ Analysis
/ Biology and Life Sciences
/ Computer and Information Sciences
/ Disease
/ Drug discovery
/ Genes
/ Indication
/ Interleukin 1
/ Interleukin 12
/ Interleukin 23
/ Machine learning
/ Medicine and Health Sciences
/ Methods
/ Performance evaluation
/ Physical Sciences
/ Physiology
/ Research and Analysis Methods
/ Target recognition
/ Therapeutic targets
2021
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An integrative network-based approach for drug target indication expansion
Journal Article
An integrative network-based approach for drug target indication expansion
2021
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Overview
The identification of a target-indication pair is regarded as the first step in a traditional drug discovery and development process. Significant investment and attrition occur during discovery and development before a molecule is shown to be safe and efficacious for the selected indication and becomes an approved drug. Many drug targets are functionally pleiotropic and might be good targets for multiple indications. Methodologies that leverage years of scientific contributions on drug targets to allow systematic evaluation of other indication opportunities are critical for both patients and drug discovery and development scientists. We introduced a network-based approach to systematically screen and prioritize disease indications for drug targets. The approach fundamentally integrates disease genomics data and protein interaction network. Further, the methodology allows for indication identification by leveraging state-of-art network algorithms to generate and compare the target and disease subnetworks. We first evaluated the performance of our method on recovering FDA approved indications for 15 randomly selected drug targets. The results showed superior performance when compared with other state-of-art approaches. Using this approach, we predicted novel indications supported by literature evidence for several highly pursued drug targets such as IL12/IL23 combination. Our results demonstrated a potential global approach for indication expansion strategies. The proposed methodology enables rapid and systematic evaluation of both individual and combined drug targets for novel indications. Additionally, this approach provides novel insights on expanding the role of genes and pathways for developing therapeutic intervention strategies.
Publisher
Public Library of Science,Public Library of Science (PLoS)
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