Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data
Abstract
:1. Introduction
2. Results
3. Discussion
3.1. Network Medicine Applied to Gene Expression Data
3.2. Highly Disrupted Genes
3.3. Notable Connections and Clusters
3.3.1. Y-Linked Regulators
3.3.2. Immune-System Involved
3.3.3. Under Expressed Regulatory Elements
3.3.4. Folate Receptors
3.3.5. Unidentified Transcripts
4. Materials and Methods
4.1. Alzheimer’s Disease Neuroimaging Initiative
4.2. Network Medicine Applied to AD Gene Expression Data
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
ADNI | Alzheimer’s Disease Neuroimaging Initiative |
CBS | Cystathionine beta synthase |
FDR | False discovery rate |
HP | Haptoglobin |
lncRNA | Long non-coding RNA |
MCI | Mild cognitive impairment |
MHC | Major Histocompatibility Complex |
NC | Normal condition |
NM | Network medicine |
PTGDS | Prostaglandin D2 synthase |
XIST | X-inactive specific transcript |
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Key | Gene | Expression in MCI 2 | Expression in AD |
---|---|---|---|
1 | [RPS4Y1] Ribosomal protein S4 Y-linked 1 Probe set: 11716411_x_at | Up | Up |
2 | [EIF1AY] eukaryotic translation initiation factor 1A Y-linked Probe set: 11720807_x_at | Up | Up |
3 | [GATA2] GATA binding protein 2 Probe set: 11722761_a_at | Down | Down p = 0.203 |
4 | [DDX3Y] DEAD (Asp-Glu-Ala-Asp) box helicase 3 Y-linked Probe set: 11724075_a_at | Up | Up |
5 | [HLA-DQA1] Major histocompatibility complex class II DQ alpha 1 Probe set: 11724799_x_at | Up | Up p = 0.694 |
6 | [USP9Y] ubiquitin specific peptidase 9 Y-linked Probe set: 11725294_at | Up | Up p = 0.194 |
7 | [KDM5D] lysine (K)-specific demethylase 5D Probe set: 11726813_a_at | Up | Up |
8 | [KDM5D] lysine (K)-specific demethylase 5D Probe set: 11726814_x_at | Up | Up |
9 | [TBC1D22B] TBC1 domain family member 22B Probe set: 11728078_a_at | Up p = 0.670 | Down |
10 | [BPI] Bactericidal/permeability-increasing protein Probe set: 11729344_at | Up p = 0.225 | Up |
11 | [ANKRD22] Ankyrin repeat domain 22 Probe set: 11732425_at | Up p = 0.334 | Up |
12 | [TMOD1] Tropomodulin 1 Probe set: 11732501_a_at | Down p = 0.587 | Down |
13 | [DEFA4] Defensin alpha 4 corticostatin Probe set:11732546_at | Up p = 0.293 | Up |
14 | [HP] Haptoglobin Probe set: 11733829_x_at | - p = 0.991 | Up |
15 | [DDX3Y] DEAD (Asp-Glu-Ala-Asp) box helicase 3 Y-linked Probe set: 11734664_x_at | Up | Up |
16 | [OSBP2] Oxysterol binding protein 2 Probe set: 11736205_a_at | Down p = 0.473 | Down |
17 | [FCRL1] Fc receptor-like 1 Probe set: 11736882_a_at | Down p = 0.641 | Down |
18 | [FCRL1] Fc receptor-like 1 Probe set: 11736883_x_at | Down p = 0.694 | Down |
19 | [FAM46C] Family with sequence similarity 46 member C Probe set: 11739338_at | Down p = 0.531 | Down |
20 | [OR2W3] (Locus via Non-standard RNA) olfactory receptor family 2 subfamily W member 3 Probe set: 11741636_at | - p = 0.843 | Down |
21 | [CACNG6] Calcium channel voltage-dependent gamma subunit 6 Probe set: 11742124_a_atex | Down | Down p = 0.616 |
22 | [FOLR3] folate receptor 3 (gamma) Probe set: 11744140_a_at | Up p = 0.645 | Up p = 0.163 |
23 | [FOLR3] folate receptor 3 (gamma) Probe set: 11744141_x_at | Up p = 0.582 | Up p = 0.137 |
24 | [CBS] Cystathionine-beta-synthase Probe set: 11744286_s_at | - p = 0.995 | Up |
25 | [HP] Haptoglobin Probe set: 11744649_x_at | - p = 0.76 | Up p = 0.141 |
26 | [CBS] Cystathionine-beta-synthase Probe set: 11744835_s_at | - p = 0.995 | Up |
27 | [KDM5D] lysine (K)-specific demethylase 5D Probe set: 11745012_a_at | Up | Up |
28 | [HLA-DQB1] Major histocompatibility complex class II DQ beta 1 Probe set: 11746804_x_at | Up | Up p = 0.46 |
29 | [DDX3Y] DEAD (Asp-Glu-Ala-Asp) box helicase 3 Y-linked Probe set: 11748424_x_at | Up | Up |
30 | [DDX3Y] DEAD (Asp-Glu-Ala-Asp) box helicase 3 Y-linked Probe set: 11749841_x_at | Up | Up |
31 | [HLA-DQA1] Major histocompatibility complex class II DQ alpha 1 Probe set: 11750528_x_at | Up | - p = 0.89 |
32 | [ENSG00000211625 || ENSG00000239951] (Matches 2 Loci; Matches Ensembl Gene) Putative uncharacterized protein ENSP00000374805 [Source:UniProtKB/TrEMBL;Acc:A6NLY3] || Ig kappa chain V-III region HAH Precursor [Source:UniProtKB/Swiss-Prot;Acc:P18135] Probe set: 11753832_x_at | Down p = 0.123 | Down |
33 | [XIST] X inactive specific transcript (non-protein coding) Probe set: 11754194_s_at | Down | Down |
34 | [EGR1] Early growth response 1 Probe set: 11754334_s_at | Down | Down |
35 | [NUDT4 || NUDT4P2 || NUDT4P1] (Matches 3 Loci) Nudix (Nucleoside diphosphate linked moiety X)-type motif 4 || nudix (nucleoside diphosphate linked moiety X)-type motif 4 pseudogene 2 || Nudix (nucleoside diphosphate linked moiety X)-type motif 4 pseudogene 1 Probe set: 11754453_s_at | - p = 0.846 | Down |
36 | [SHISA4] shisa family member 4 Probe set: 11756240_a_at | Down p = 0.641 | Down |
37 | [PTGDS] prostaglandin D2 synthase 21kDa (brain) Probe set: 11756587_a_at | - p = 0.853 | Up |
38 | [HP] Haptoglobin Probe set: 11757277_x_at | - p = 0.932 | Up |
39 | [XIST] X inactive specific transcript (non-protein coding) Probe set: 11757733_s_at | Down | Down |
40 | [XIST] X inactive specific transcript (non-protein coding) Probe set: 11757857_s_at | Down | Down |
41 | [TRIM10] tripartite motif containing 10 Probe set: 11758611_s_at | Up p = 0.647 | Down |
42 | (Matches Non-standard RNA) JARID1C protein (JARID1C) mRNA complete cds alternatively spliced Probe set: 11761133_at | Down | Down |
43 | [HLA-DQB1] (POOR HIT 44%) Major histocompatibility complex class II DQ beta 1 Probe set: 11762641_x_at | Up | Up p = 0.56 |
44 | (DEPRECATED TARGET; Matches RefSeq) (Deprecated) PREDICTED: Homo sapiens similar to hCG2042707 (LOC650405) || (Deprecated) PREDICTED: Homo sapiens similar to pre-B lymphocyte gene 1 (LOC652493) || (Deprecated) PREDICTED: Homo sapiens similar to hCG26659 (LOC100291464) Probe set: 11763222_x_at | Down p = 0.316 | Down |
45 | [ENSG00000211663] (Matches Ensembl Gene) V2-13 protein Fragment [Source:UniProtKB/TrEMBL; Acc:Q5NV73] Probe set: 11763229_x_at | Down p = 0.331 | Down |
46 | [ENSG00000242534 || ENSG00000244116] (Matches 2 Loci; Matches Ensembl Gene) immunoglobulin kappa variable 2D-28 [ENST00000453166 ENST00000558026] || immunoglobulin kappa variable 2-28 [ENST00000482769] | Up p = 0.614 | Down p = 0.122 |
47 | [ENSG00000211663] (Matches Ensembl Gene) V2-13 protein Fragment [Source:UniProtKB/TrEMBL;Acc:Q5NV73] Probe set: 11763255_x_at | Down p = 0.279 | Down |
48 | [ENSG00000211663] (Matches Ensembl Gene) V2-13 protein Fragment [Source:UniProtKB/TrEMBL;Acc:Q5NV73] Probe set: 11763551_x_at | Down p = 0.332 | Down |
49 | (Matches Non-standard RNA) mRNA; cDNA DKFZp686L12190 (from clone DKFZp686L12190): Probe set: 11763837_s_at | Up | Up |
50 | [TXLNG2P] (Matches Ensembl Gene) Uncharacterized protein CYorf15B (Lipopolysaccaride-specific response 5-like protein) [Source:UniProtKB/Swiss-Prot;Acc:Q9BZA4] Probe set: 11764064_s_at | Up | Up |
Gene | DyNet Rewiring Score |
---|---|
[HP] Haptoglobin Probe set: 11757277_x_at | 8.33 |
[FOLR3] folate receptor 3 (gamma) Probe set: 11744141_x_at | 8.00 |
[FOLR3] folate receptor 3 (gamma) Probe set: 11744140_a_at | 8.00 |
[NUDT4 || NUDT4P2 || NUDT4P1] (Matches 3 Loci) Nudix (Nucleoside diphosphate linked moiety X)-type motif 4 || nudix (nucleoside diphosphate linked moiety X)-type motif 4 pseudogene 2 || Nudix (nucleoside diphosphate linked moiety X)-type motif 4 pseudogene 1HP Probe set: 11754453_s_at | 7.00 |
[HP] Haptoglobin Probe set: 11744649_x_at | 7.00 |
[HP] Haptoglobin Probe set: 11733829_x_at | 7.00 |
[SHISA4] shisa family member 4 Probe set: 11756240_a_at | 6.67 |
[CBS] Cystathionine-beta-synthase Probe set: 11744835_s_at | 6.00 |
[TBC1D22B] TBC1 domain family member 22B Probe set: 11728078_a_at | 5.67 |
[CBS] Cystathionine-beta-synthase Probe set: 11744286_s_at | 5.67 |
Gene | DyNet Rewiring Score |
---|---|
[GATA2] GATA binding protein 2 Probe set: 11722761_a_at | 8.00 |
[PTGDS] prostaglandin D2 synthase 21kDa (brain) Probe set: 11756587_a_at | 6.33 |
[ANKRD22] Ankyrin repeat domain 22 Probe set: 11732425_at | 6.33 |
[SHISA4] shisa family member 4 Probe set: 11756240_a_at | 5.67 |
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Cohen, D.; Pilozzi, A.; Huang, X. Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data. Int. J. Mol. Sci. 2020, 21, 332. https://doi.org/10.3390/ijms21010332
Cohen D, Pilozzi A, Huang X. Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data. International Journal of Molecular Sciences. 2020; 21(1):332. https://doi.org/10.3390/ijms21010332
Chicago/Turabian StyleCohen, David, Alexander Pilozzi, and Xudong Huang. 2020. "Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data" International Journal of Molecular Sciences 21, no. 1: 332. https://doi.org/10.3390/ijms21010332