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).
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.
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.
This study shows that GES and CMap can be used as tools to repurpose drugs for BD.
Pharmacology, Toxicology and Pharmaceutical Science
3
8%
Psychology
3
8%
Neuroscience
3
8%
Computer Science
2
5%
Other
5
14%
Unknown
14
38%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 August 2018.
All research outputs
#21,346,868
of 34,040,673 outputs
Outputs from World Journal of Biological Psychiatry
#440
of 856 outputs
Outputs of similar age
#212,608
of 371,846 outputs
Outputs of similar age from World Journal of Biological Psychiatry
#6
of 9 outputs
Altmetric has tracked 34,040,673 research outputs across all sources so far. This one is in the 36th percentile – i.e., 36% of other outputs scored the same or lower than it.
So far Altmetric has tracked 856 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.1. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 371,846 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.
