Novel methods for integration and visualization of genomics and genetics data in Alzheimer's disease.
Alzheimer Disease
/ genetics
Brain
/ pathology
Calcineurin
Calcium Signaling
Focal Adhesion Kinase 2
/ genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
Humans
Longitudinal Studies
Membrane Transport Proteins
/ genetics
Mitochondrial Precursor Protein Import Complex Proteins
Polymorphism, Single Nucleotide
Alzheimer's disease
Calcineurin
Calcium signaling pathway
Data visualization
Genomics
PTK2B
TOMM40
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
07
09
2018
revised:
12
12
2018
accepted:
18
01
2019
pubmed:
3
4
2019
medline:
23
6
2020
entrez:
3
4
2019
Statut:
ppublish
Résumé
Numerous omics studies have been conducted to understand the molecular networks involved in Alzheimer's disease (AD), but the pathophysiology is still not completely understood; new approaches that enable neuroscientists to better interpret the results of omics analysis are required. We have developed advanced methods to analyze and visualize publicly-available genomics and genetics data. The tools include a composite clinical-neuropathological score for defining AD, gene expression maps in the brain, and networks integrating omics data to understand the impact of polymorphisms on AD pathways. We have analyzed over 50 public human gene expression data sets, spanning 19 different brain regions and encompassing three separate cohorts. We integrated genome-wide association studies with expression data to identify important genes in the pathophysiology of AD, which provides further insight into the calcium signaling and calcineurin pathways. Biologists can use these freely-available tools to obtain a comprehensive, information-rich view of the pathways in AD.
Identifiants
pubmed: 30935898
pii: S1552-5260(19)30032-9
doi: 10.1016/j.jalz.2019.01.011
pmc: PMC6664293
mid: NIHMS1035023
pii:
doi:
Substances chimiques
Membrane Transport Proteins
0
Mitochondrial Precursor Protein Import Complex Proteins
0
TOMM40 protein, human
0
Focal Adhesion Kinase 2
EC 2.7.10.2
PTK2B protein, human
EC 2.7.10.2
Calcineurin
EC 3.1.3.16
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
788-798Subventions
Organisme : NIA NIH HHS
ID : U01 AG046152
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG042210
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG039478
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062421
Pays : United States
Organisme : NINDS NIH HHS
ID : U18 NS082140
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032990
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS080820
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG034374
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017216
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018023
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS078009
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG041689
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005134
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG036042
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG034504
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG041232
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003949
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS072026
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025711
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG036836
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Informations de copyright
Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Références
Transl Res. 2015 Jan;165(1):200-20
pubmed: 24905038
Alzheimers Dement. 2017 Feb;13(2):178-182.e17
pubmed: 28061328
Nat Neurosci. 2018 Jun;21(6):811-819
pubmed: 29802388
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Curr Alzheimer Res. 2012 Jul;9(6):646-63
pubmed: 22471867
Nat Genet. 2018 Nov;50(11):1584-1592
pubmed: 30297968
Sci Signal. 2016 Sep 06;9(444):ra89
pubmed: 27601731
Alzheimers Dement. 2009 Jan;5(1):1-4
pubmed: 19118801
J Neurosci. 2010 Feb 17;30(7):2636-49
pubmed: 20164348
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
Alzheimers Dement. 2018 Apr;14(4):532-534
pubmed: 29653605
Expert Opin Ther Targets. 2016;20(4):389-91
pubmed: 26853544
Neuron. 2018 Jul 11;99(1):64-82.e7
pubmed: 29937276
Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):E1289-E1298
pubmed: 29358399
Neurology. 1991 Apr;41(4):479-86
pubmed: 2011243
Am J Hum Genet. 2009 Apr;84(4):445-58
pubmed: 19361613
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Methods Mol Biol. 2018;1750:341-351
pubmed: 29512084
Clin Neuropsychol. 2015;29(7):1002-9
pubmed: 26617181
Science. 1997 Sep 5;277(5331):1511-5
pubmed: 9278515
Curr Alzheimer Res. 2012 Jul;9(6):628-45
pubmed: 22471860
Science. 1984 Sep 14;225(4667):1168-70
pubmed: 6474172
Chin Med J (Engl). 2018 Jul 5;131(13):1618-1624
pubmed: 29941717
Front Aging Neurosci. 2018 Jul 09;10:199
pubmed: 30038565
Nat Rev Neurol. 2016 Jul;12(7):413-27
pubmed: 27282653
J Alzheimers Dis Parkinsonism. 2017 Aug;7(5):
pubmed: 29214114
Neuron. 2014 May 21;82(4):756-71
pubmed: 24853936
Genome Med. 2016 Nov 1;8(1):104
pubmed: 27799057
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W214-20
pubmed: 20576703
PLoS Genet. 2012;8(6):e1002707
pubmed: 22685416
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Nat Genet. 2009 Feb;41(2):192-8
pubmed: 19136949
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Nucleic Acids Res. 2016 Jan 4;44(D1):D457-62
pubmed: 26476454
Mol Psychiatry. 2018 Jun;23(6):1521-1529
pubmed: 28322283
Nature. 2015 Sep 17;525(7569):339-44
pubmed: 26344197
Genome Biol. 2014 Feb 03;15(2):R29
pubmed: 24485249
J Alzheimers Dis. 2010;19(3):781-93
pubmed: 20157236
IEEE Trans Vis Comput Graph. 2011 Dec;17(12):2301-9
pubmed: 22034350
Curr Genomics. 2010 Dec;11(8):618-33
pubmed: 21629439
Cell. 2009 Jul 10;138(1):210, 210.e1
pubmed: 19596245
Neuromolecular Med. 2013 Jun;15(2):279-87
pubmed: 23288655
J Neurosci. 1996 Jul 15;16(14):4491-500
pubmed: 8699259
Sci Data. 2016 Oct 11;3:160089
pubmed: 27727239
Genomics. 2007 Jun;89(6):655-65
pubmed: 17434289
J Neurochem. 2018 Oct;147(1):24-39
pubmed: 29806693
Brain. 2014 Feb;137(Pt 2):537-52
pubmed: 24401760
Mol Neurodegener. 2011 Aug 26;6(1):63
pubmed: 21871088
Alzheimers Dement. 2012 Jan;8(1):1-13
pubmed: 22265587
JAMA Neurol. 2015 Jan;72(1):15-24
pubmed: 25365775
J Neurochem. 2018 Oct;147(1):8-11
pubmed: 30256415
Neuron. 2008 Jul 31;59(2):214-25
pubmed: 18667150
Alzheimers Dement. 2017 Oct;13(10):1133-1142
pubmed: 28242297
Cell. 2013 Apr 25;153(3):707-20
pubmed: 23622250
Nat Genet. 2007 Dec;39(12):1494-9
pubmed: 17982457