Gene, cell type, and drug prioritization analysis suggest genetic basis for the utility of diuretics in treating Alzheimer disease.
GCDPipe
GWAS
Gene prioritization
Machine learning
Journal
HGG advances
ISSN: 2666-2477
Titre abrégé: HGG Adv
Pays: United States
ID NLM: 101772885
Informations de publication
Date de publication:
13 07 2023
13 07 2023
Historique:
received:
09
08
2022
accepted:
25
04
2023
medline:
1
6
2023
pubmed:
30
5
2023
entrez:
30
5
2023
Statut:
epublish
Résumé
We introduce a user-friendly tool for risk gene, cell type, and drug prioritization for complex traits: GCDPipe. It uses gene-level GWAS-derived data and gene expression data to train a model for the identification of disease risk genes and relevant cell types. Gene prioritization information is then coupled with known drug target data to search for applicable drug agents based on their estimated functional effects on the identified risk genes. We illustrate the utility of our approach in different settings: identification of the cell types, implicated in disease pathogenesis, was tested in inflammatory bowel disease (IBD) and Alzheimer disease (AD); gene target and drug prioritization was tested in IBD and schizophrenia. The analysis of phenotypes with known disease-affected cell types and/or existing drug candidates shows that GCDPipe is an effective tool to unify genetic risk factors with cellular context and known drug targets. Next, analysis of the AD data with GCDPipe suggested that gene targets of diuretics, as an Anatomical Therapeutic Chemical drug subgroup, are significantly enriched among the genes prioritized by GCDPipe, indicating their possible effect on the course of the disease.
Identifiants
pubmed: 37250495
doi: 10.1016/j.xhgg.2023.100203
pii: S2666-2477(23)00035-0
pmc: PMC10209737
doi:
Substances chimiques
Diuretics
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100203Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Dig Dis Sci. 2017 Sep;62(9):2208-2210
pubmed: 28646283
Sci Rep. 2017 Sep 28;7(1):12390
pubmed: 28959040
JAMA Psychiatry. 2019 Sep 1;76(9):914-923
pubmed: 31166595
Nat Commun. 2019 Jul 19;10(1):3222
pubmed: 31324783
Elife. 2018 May 30;7:
pubmed: 29846171
J Crohns Colitis. 2018 Mar 28;12(4):465-475
pubmed: 29211912
Neurobiol Aging. 2014 Nov;35(11):2429-2435
pubmed: 24910391
Am J Psychiatry. 2012 Oct;169(10):1082-91
pubmed: 22983435
Am J Hum Genet. 2017 Nov 2;101(5):686-699
pubmed: 29106824
Front Neurosci. 2020 Jun 03;14:542
pubmed: 32655348
Schizophr Bull. 2014 Sep;40(5):1053-61
pubmed: 24837792
Nat Genet. 2015 Sep;47(9):1091-8
pubmed: 26258848
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
pubmed: 10592173
Nat Genet. 2018 Apr;50(4):621-629
pubmed: 29632380
Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082
pubmed: 29126136
Psychol Med. 2016 Sep;46(12):2501-12
pubmed: 27328999
Sci Rep. 2020 Jan 21;10(1):879
pubmed: 31964963
Psychopharmacology (Berl). 2011 May;215(1):149-63
pubmed: 21181124
Nat Genet. 2016 Mar;48(3):245-52
pubmed: 26854917
ACS Chem Neurosci. 2020 Dec 16;11(24):4152-4168
pubmed: 33225679
BMC Bioinformatics. 2020 Jun 5;21(1):231
pubmed: 32503412
Nucleic Acids Res. 2021 Jan 8;49(D1):D1311-D1320
pubmed: 33045747
Nat Genet. 2019 Jul;51(7):1082-1091
pubmed: 31253980
Biol Psychiatry. 2016 Apr 1;79(7):595-603
pubmed: 26210060
Ment Health Clin. 2018 Mar 26;8(1):33-40
pubmed: 29955543
Science. 2021 Apr 2;372(6537):33-34
pubmed: 33795448
Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9089-94
pubmed: 22615377
J Mol Cell Cardiol. 2015 Dec;89(Pt B):335-48
pubmed: 26454161
Hum Mol Genet. 2021 Apr 26;30(3-4):294-304
pubmed: 33577681
J Cell Biol. 2018 Feb 5;217(2):459-472
pubmed: 29196460
Bioinformatics. 2019 Oct 1;35(19):3821-3823
pubmed: 30859178
Mol Psychiatry. 2021 Jan;26(1):203-217
pubmed: 32404946
Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:625-648
pubmed: 28992433
FASEB J. 2013 Jun;27(6):2458-67
pubmed: 23504710
Nat Rev Genet. 2021 Oct;22(10):658-671
pubmed: 34302145
Comput Struct Biotechnol J. 2020 Jun 12;18:1639-1650
pubmed: 32670504
Neurobiol Dis. 2013 May;53:10-7
pubmed: 23220619
Nat Aging. 2021 Oct;1(10):932-947
pubmed: 36172600
Elife. 2020 Dec 29;9:
pubmed: 33372656
Eur J Hum Genet. 2021 Oct;29(10):1527-1535
pubmed: 34276057
Inflamm Bowel Dis. 2017 Sep;23(9):1516-1523
pubmed: 28795970
PLoS One. 2013 Apr 30;8(4):e62445
pubmed: 23638087
Schizophr Res. 2005 Jul 15;76(2-3):135-57
pubmed: 15949648
Bioinformatics. 2019 Jul 15;35(14):2515-2517
pubmed: 30517594
Transl Psychiatry. 2012 Mar 20;2:e94
pubmed: 22832859
BMC Bioinformatics. 2013 Aug 16;14:249
pubmed: 23947436
Protein Cell. 2020 Apr;11(4):286-291
pubmed: 31907793