The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder

Kidnapillai, Srisaiyini, Bortolasci, Chiara C., Udawela, Madhara, Panizzutti, Bruna, Spolding, Briana, Connor, Timothy, Sanigorski, Andrew, Dean, Olivia, Crowley, Tamsyn, Jamain, Stephane, Gray, Laura, Scarr, Elizabeth, Leboyer, Marion, Dean, Brian, Berk, Michael and Walder, Ken 2018, The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder, World journal of biological psychiatry, pp. 1-9, doi: 10.1080/15622975.2018.1492734.

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Title The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder
Author(s) Kidnapillai, SrisaiyiniORCID iD for Kidnapillai, Srisaiyini
Bortolasci, Chiara C.ORCID iD for Bortolasci, Chiara C.
Udawela, Madhara
Panizzutti, Bruna
Spolding, Briana
Connor, Timothy
Sanigorski, AndrewORCID iD for Sanigorski, Andrew
Dean, OliviaORCID iD for Dean, Olivia
Crowley, TamsynORCID iD for Crowley, Tamsyn
Jamain, Stephane
Gray, LauraORCID iD for Gray, Laura
Scarr, Elizabeth
Leboyer, Marion
Dean, Brian
Berk, MichaelORCID iD for Berk, Michael
Walder, KenORCID iD for Walder, Ken
Journal name World journal of biological psychiatry
Start page 1
End page 9
Total pages 9
Publisher Taylor & Francis
Place of publication London, Eng.
Publication date 2018
ISSN 1814-1412
Keyword(s) Bipolar disorder
drug discovery
drug repurposing
gene expression signature
Summary OBJECTIVES: To create a gene expression signature (GES) to represent the biological effects of a combination of known drugs for bipolar disorder (BD) on cultured human neuronal cells (NT2-N) and rat brains, which also has evidence of differential expression in individuals with BD. To use the GES to identify new drugs for BD using Connectivity Map (CMap). METHODS: NT2-N (n = 20) cells and rats (n = 8) were treated with a BD drug combination (lithium, valproate, quetiapine and lamotrigine) or vehicle for 24 and 6 h, respectively. Following next-generation sequencing, the differential expression of genes was assessed using edgeR in R. The derived GES was compared to differentially expressed genes in post-mortem brains of individuals with BD. The GES was then used in CMap analysis to identify similarly acting drugs. RESULTS: A total of 88 genes showed evidence of differential expression in response to the drug combination in both models, and therefore comprised the GES. Six of these genes showed evidence of differential expression in post-mortem brains of individuals with BD. CMap analysis identified 10 compounds (camptothecin, chlorambucil, flupenthixol, valdecoxib, rescinnamine, GW-8510, cinnarizine, lomustine, mifepristone and nimesulide) acting similarly to the BD drug combination. CONCLUSIONS: This study shows that GES and CMap can be used as tools to repurpose drugs for BD.
Notes In Press
Language eng
DOI 10.1080/15622975.2018.1492734
Field of Research 1103 Clinical Sciences
1109 Neurosciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, Informa
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Document type: Journal Article
Collection: School of Medicine
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