PMID- 32925069
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20210920
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 78
IP  - 1
DP  - 2020
TI  - Data-Driven Modeling of Knowledge Assemblies in Understanding Comorbidity Between 
      Type 2 Diabetes Mellitus and Alzheimer's Disease.
PG  - 87-95
LID - 10.3233/JAD-200752 [doi]
AB  - BACKGROUND: Recent studies have suggested comorbid association between 
      Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) through 
      identification of shared molecular mechanisms. However, the inference is 
      pre-dominantly literature-based and lacks interpretation of pre-disposed genomic 
      variants and transcriptomic measurables. OBJECTIVE: In this study, we aim to 
      identify shared genetic variants and dysregulated genes in AD and T2DM and 
      explore their functional roles in the comorbidity between the diseases. METHODS: 
      The genetic variants for AD and T2DM were retrieved from GWAS catalog, GWAS 
      central, dbSNP, and DisGeNet and subjected to linkage disequilibrium analysis. 
      Next, shared variants were prioritized using RegulomeDB and Polyphen-2. 
      Afterwards, a knowledge assembly embedding prioritized variants and their 
      corresponding genes was created by mining relevant literature using Biological 
      Expression Language. Finally, coherently perturbed genes from gene expression 
      meta-analysis were mapped to the knowledge assembly to pinpoint biological 
      entities and processes and depict a mechanistic link between AD and T2DM. 
      RESULTS: Our analysis identified four genes (i.e., ABCG1, COMT, MMP9, and SOD2) 
      that could have dual roles in both AD and T2DM. Using cartoon representation, we 
      have illustrated a set of causal events surrounding these genes which are 
      associated to biological processes such as oxidative stress, insulin resistance, 
      apoptosis and cognition. CONCLUSION: Our approach of using data as the driving 
      force for unraveling disease etiologies eliminates literature bias and enables 
      identification of novel entities that serve as the bridge between comorbid 
      conditions.
FAU - Karki, Reagon
AU  - Karki R
AD  - Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific 
      Computing (SCAI), Sankt Augustin, Germany.
AD  - Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn-Aachen International Center 
      for IT, Bonn, Germany.
FAU - Madan, Sumit
AU  - Madan S
AD  - Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific 
      Computing (SCAI), Sankt Augustin, Germany.
FAU - Gadiya, Yojana
AU  - Gadiya Y
AD  - Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific 
      Computing (SCAI), Sankt Augustin, Germany.
AD  - Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn-Aachen International Center 
      for IT, Bonn, Germany.
FAU - Domingo-Fernandez, Daniel
AU  - Domingo-Fernandez D
AD  - Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific 
      Computing (SCAI), Sankt Augustin, Germany.
FAU - Kodamullil, Alpha Tom
AU  - Kodamullil AT
AD  - Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific 
      Computing (SCAI), Sankt Augustin, Germany.
FAU - Hofmann-Apitius, Martin
AU  - Hofmann-Apitius M
AD  - Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific 
      Computing (SCAI), Sankt Augustin, Germany.
AD  - Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn-Aachen International Center 
      for IT, Bonn, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
SB  - IM
MH  - Alzheimer Disease/*genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Models, Biological
PMC - PMC7683056
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - comorbidity
OT  - systems biology
OT  - type 2 diabetes mellitus
COIS- Authors' disclosures available online 
      (https://www.j-alz.com/manuscript-disclosures/20-0752r1).
EDAT- 2020/09/15 06:00
MHDA- 2021/09/21 06:00
PMCR- 2020/11/23
CRDT- 2020/09/14 15:42
PHST- 2020/09/15 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2020/09/14 15:42 [entrez]
PHST- 2020/11/23 00:00 [pmc-release]
AID - JAD200752 [pii]
AID - 10.3233/JAD-200752 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2020;78(1):87-95. doi: 10.3233/JAD-200752.