Drug target mapping and tractability analysis of borderline personality disorder

This repository includes the code used to assess druggability and tractability of prioritized genes based on the latest borderline personality disorder (bpd) GWAS.

The following gene symbols/ Ensembl IDs were queried:

Chromosome	Position	SNP	Ensembl Gene ID	Gene Symbol
3	71266885	rs6549383	ENSG00000114861	FOXP1
5	155856538	rs2135029	ENSG00000170624	SGCD
7	114110568	rs4727799	ENSG00000128573	FOXP2
9	140251458	rs73581580	ENSG00000187609	EXD3
12	109988891	rs7304862	ENSG00000110906	KCTD10
12	109988891	rs7304862	ENSG00000151148	UBE3B
12	109988891	rs7304862	ENSG00000139428	MMAB
12	109988891	rs7304862	ENSG00000110921	MVK
12	109988891	rs7304862	ENSG00000174527	MYO1H

Add NRARP, NOXA1, CCDC71 and DEPDC1B

Open Targets (ot) drug targets and tractability

We extracted data from the Open Targets Platform using the provided GraphSGL API in R to query the platform.
The code used to extract the data on available drug targets and tractability are included in 1_opentargets_query.r.

The data sources Open Targets (e.g. ChEMBL) are detailed here:
Open Targets tractability documentation
Drug target annotation documentation

No genes in the list were identified as drug targets based on the data sources included in Open Targets
The results of the tractability query are shown in tractability_plot.jpeg generated using 2_tileplot_tractability.r
There were not tractability results for MYO1H

GREP: drug target enrichment

Additionally, we used GREP to assess drug target enrichment across clinical ATC or ICD categories.
As already highlighted by the OpenTargets query none of the genes are known drug targets. GREP thus found no enrichment in any category.
This is the Link to the tool:
https://github.com/saorisakaue/GREP

DGIdb: Drug gene interaction

Finally, we queried The Drug Gene Interaction Database which yielded the following results:

gene	drug	regulatory approval	indication	interaction score
MYO1H	LITHIUM	Approved		1.438537899903974
MVK	ALENDRONATE SODIUM	Approved	Bisphosphonates	13.10667864356954

The drug-gene interaction annotation for MYO1H is based on ConLiGen: doi:10.1001/jamapsychiatry.2017.3433
https://www.pharmgkb.org/gene/PA31404/related