Design of efficient computational workflows for in silico drug repurposing.
Here, we provide a comprehensive overview of the current status of in silico repurposing methods by establishing links between current technological trends, data availability and characteristics of the algorithms used in these methods. Using the case of the computational repurposing of fasudil as an alternative autophagy enhancer, we suggest a generic modular organization of a repurposing workflow. We also review 3D structure-based, similarity-based, inference-based and machine learning (ML)-based methods. We summarize the advantages and disadvantages of these methods to emphasize three current technical challenges. We finish by discussing current directions of research, including possibilities offered by new methods, such as deep learning.
Insilico Medicine Inc., Johns Hopkins University, ETC, B301, MD 21218, USA. Electronic address: vanhaelen@insilicomedicine.com.
Quentin
Q
Vanhaelen
Insilico Medicine Inc., Johns Hopkins University, ETC, B301, MD 21218, USA.
Polina
P
Mamoshina
Insilico Medicine Inc., Johns Hopkins University, ETC, B301, MD 21218, USA.
Alexander M
AM
Aliper
Insilico Medicine Inc., Johns Hopkins University, ETC, B301, MD 21218, USA.
Artem
A
Artemov
Insilico Medicine Inc., Johns Hopkins University, ETC, B301, MD 21218, USA.
Ksenia
K
Lezhnina
Insilico Medicine Inc., Johns Hopkins University, ETC, B301, MD 21218, USA.
Ivan
I
Ozerov
BioTime Inc., 1010 Atlantic Avenue, 102, Alameda, CA 94501, USA.
Ivan
I
Labat
Insilico Medicine Inc., Johns Hopkins University, ETC, B301, MD 21218, USA.
Alex
A
Zhavoronkov
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D003198:Computer Simulation; D058492:Drug Repositioning; D006801:Humans; D057188:Workflow
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil