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Integrative Omics for Informed Drug Repurposing: Targeting CNS Disorders

View ORCID ProfileRammohan Shukla, Nicholas D Henkel, Khaled Alganem, Abdul-rizaq Hamoud, James Reigle, Rawan S Alnafisah, Hunter M Eby, Ali S Imami, Justin Creeden, Scott A Miruzzi, Jaroslaw Meller, Robert E. Mccullumsmith
doi: https://doi.org/10.1101/2020.04.24.060392
Rammohan Shukla
1Department of Neurosciences, University of Toledo, Toledo OH, USA
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  • For correspondence: rammohan.shukla@utoledo.edu
Nicholas D Henkel
1Department of Neurosciences, University of Toledo, Toledo OH, USA
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Khaled Alganem
1Department of Neurosciences, University of Toledo, Toledo OH, USA
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Abdul-rizaq Hamoud
1Department of Neurosciences, University of Toledo, Toledo OH, USA
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James Reigle
2Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
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Rawan S Alnafisah
1Department of Neurosciences, University of Toledo, Toledo OH, USA
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Hunter M Eby
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Ali S Imami
1Department of Neurosciences, University of Toledo, Toledo OH, USA
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Justin Creeden
1Department of Neurosciences, University of Toledo, Toledo OH, USA
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Scott A Miruzzi
1Department of Neurosciences, University of Toledo, Toledo OH, USA
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Jaroslaw Meller
2Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
3Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA
4Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio
5Department of Electrical Engineering and Computing Systems, University of Cincinnati College of Medicine, Cincinnati, Ohio
6Department of Informatics, Nicolaus Copernicus University, Torun, Poland
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Robert E. Mccullumsmith
1Department of Neurosciences, University of Toledo, Toledo OH, USA
7Neurosciences Institute, ProMedica, Toledo, OH, USA
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Abstract

The treatment of CNS disorders, and in particular psychiatric illnesses, lacks disease-altering therapeutics for many conditions. This is likely due to regulatory challenges involving the high cost and slow-pace of drug development for CNS disorders as well as due to limited understanding of disease causality. Repurposing drugs for new indications have lower cost and shorter development timeline compared to that of de novo drug development. Historically, empirical drug-repurposing is a standard practice in psychiatry; however, recent advances in characterizing molecules with their structural and transcriptomic signatures along with ensemble of data analysis approaches, provides informed and cost-effective repurposing strategies that ameliorate the regulatory challenges. In addition, the potential to incorporate ontological approaches along with signature-based repurposing techniques addresses the various knowledge-based challenges associated with CNS drug development. In this review we primarily discuss signature-based in silico approaches to drug repurposing, and its integration with data science platforms for evidence-based drug repurposing. We contrast various in silico and empirical approaches and discuss possible avenues to improve the clinical relevance. These concepts provide a promising new translational avenue for developing new therapies for difficult to treat disorders, and offer the possibility of connecting drug discovery platforms and big data analytics with personalized disease signatures.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 25, 2020.
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Integrative Omics for Informed Drug Repurposing: Targeting CNS Disorders
Rammohan Shukla, Nicholas D Henkel, Khaled Alganem, Abdul-rizaq Hamoud, James Reigle, Rawan S Alnafisah, Hunter M Eby, Ali S Imami, Justin Creeden, Scott A Miruzzi, Jaroslaw Meller, Robert E. Mccullumsmith
bioRxiv 2020.04.24.060392; doi: https://doi.org/10.1101/2020.04.24.060392
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Integrative Omics for Informed Drug Repurposing: Targeting CNS Disorders
Rammohan Shukla, Nicholas D Henkel, Khaled Alganem, Abdul-rizaq Hamoud, James Reigle, Rawan S Alnafisah, Hunter M Eby, Ali S Imami, Justin Creeden, Scott A Miruzzi, Jaroslaw Meller, Robert E. Mccullumsmith
bioRxiv 2020.04.24.060392; doi: https://doi.org/10.1101/2020.04.24.060392

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