Analysis of Differentially Expressed Genes That Aggravate Metabolic Diseases in Depression
Abstract
:1. Introduction
2. Methods and Materials
2.1. Overview of the Study
2.2. Retrieval of Microarray Datasets
2.3. Differential Gene Expression Analysis and Validation with Random Unrelated Diseases
2.4. Gene Set Enrichment Analysis
2.5. Ontology Pathway
2.6. Protein–Protein Interaction (PPI) Network and Hub-Gene Identification
2.7. Prediction of the Master Transcription Factors (TFs)
2.8. OMIM Disease and OMIM Expanded Database
2.9. Validation of the Common DEGs with other Depression-Related Datasets
2.10. Statistical Analysis
3. Results
3.1. Identification of DEGs
3.2. KEGG Pathway Analysis
3.3. Gene Ontological Pathway Analysis
3.4. PPI Interactions
3.5. MCODE
3.6. TFs Prediction by iRegulon
3.7. Validation by OMIM Disease and dbGap
3.8. Validation of the Commonly Expressed DEGs with Other Depression-Related Datasets
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
DEGs | Differentially Expressed Genes |
Log FC | Log Fold Change |
GO | Gene Ontology |
GEO | Gene Expression Omnibus |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
PPI | Protein–Protein Interaction |
DAVID | Database for Annotation, Visualization, and Integrated Discovery |
NASH | Nonalcoholic Steatohepatitis |
MDD | Major Depressive Disorder |
NCBI | National Center for Biotechnology Information |
OMIM | Online Mendelian Inheritance in Man |
HPA | Hypothalamic–pituitary–adrenal |
CRH | Corticotrophin-releasing hormone |
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SL | Disease Name | GEO Accession | Sample | Platform | |
---|---|---|---|---|---|
Healthy | Disease | ||||
1 | Depression | GSE58430 | 6 | 6 | GPL14550 |
3 | Obesity | GSE128021 | 3 | 3 | GPL10558 |
2 | Diabetes | GSE43950 | 5 | 4 | GPL10379 |
4 | NASH | GSE43600 | 8 | 10 | GPL10558 |
Disease Name | GEO Accession | Disease Name | GEO Accession | % of Upregulated Common DEGs | % of Down Regulated Common DEGs |
---|---|---|---|---|---|
Depression | GSE58430 | Obesity | GSE128021 | 3.5 | 4.6 |
Diabetes | GSE43950 | 5.1 | 3.9 | ||
NASH | GSE43600 | 3.4 | 2.8 | ||
Influenza | GSE111449 | Obesity | GSE128021 | 1.2 | 1.0 |
Diabetes | GSE43950 | 0.7 | 0.6 | ||
NASH | GSE46300 | 1.6 | 0.9 |
GO Pathways | Adj p-Value | Genes | ||
---|---|---|---|---|
Molecular functions | RNA polymerase II regulatory-region sequence-specific DNA binding | (GO:0000977) | 0.000059725 | ELK4;CUX1;MAX;DEAF1;MAZ;TFEC;HSF1;MXI1;PRDM2;NKX2-5;JUNB |
alpha-(1->3)-fucosyltransferase activity | (GO:0046920) | 0.000866475 | FUT7;FUT4 | |
G-protein-activated inward rectifier potassium channel activity | (GO:0015467) | 0.001382294 | KCNJ15;KCNJ2 | |
fucosyltransferase activity | (GO:0008417) | 0.002369586 | FUT7;FUT4 | |
titin binding | (GO:0031432) | 0.002754338 | CAMK2D;OBSCN | |
Biological pathways | cellular response to type I interferon | (GO:0071357) | 0.000033205 | RSAD2;OAS1;IFIT1;XAF1;IFIT3 |
type I interferon signaling pathway | (GO:0060337) | 0.000033205 | RSAD2;OAS1;IFIT1;XAF1;IFIT3 | |
cytokine-mediated signaling pathway | (GO:0019221) | 0.000244271 | CAMK2D;RSAD2;OAS1;IRAK2;TNFRSF10C;CXCL1;IFIT1;XAF1;SOS1;PTGS2;JUNB;IFIT3 | |
insulin secretion involved in cellular response to glucose stimulus | (GO:0035773) | 0.000467629 | PTPRN;RAB11B | |
L-fucose metabolic process | (GO:0042354) | 0.001109929 | FUT7;FUT4 | |
Cellular components | Golgi subcompartment | (GO:0098791) | 0.001591532 | SLC35A2;FUT7;CUX1;CDH1;B3GNT5;RAB12;AP1B1;MAN1C1;FUT4 |
spindle pole | (GO:0000922) | 0.003189301 | SGO1;STAG2;HSF1;CEP128 | |
tertiary granule lumen | (GO:1904724) | 0.003721186 | CDA;CXCL1;PTX3 | |
nuclear transcription-factor complex | (GO:0044798) | 0.007595372 | MAX;MXI1;NKX2-5 | |
mitotic spindle pole | (GO:0097431) | 0.008720051 | STAG2;HSF1 |
GO Pathways | Adj p-Value | Genes | ||
---|---|---|---|---|
Molecular functions | interleukin-1 receptor binding | (GO:0005149) | 0.001725028 | IL1RN;IL1B |
peptidoglycan binding | (GO:0042834) | 0.001966159 | NOD2;TLR2 | |
phosphatidylinositol-4,5-bisphosphate 3-kinase activity | (GO:0046934) | 0.002844067 | PIK3CD;HBEGF;PIK3R5 | |
phosphatidylinositol bisphosphate kinase activity | (GO:0052813) | 0.00321474 | PIK3CD;HBEGF;PIK3R5 | |
chemokine receptor activity | (GO:0004950) | 0.003394807 | CXCR1;CXCR2 | |
Biological pathways | neutrophil degranulation | (GO:0043312) | 0.0000000834 | CDA;TNFAIP6;MME;FPR1;CXCL1;CXCR1;ALOX5;QPCT;CXCR2;CYSTM1;PTX3;S100A11;TLR2 |
neutrophil activation involved in immune response | (GO:0002283) | 0.0000000918 | CDA;TNFAIP6;MME;FPR1;CXCL1;CXCR1;ALOX5;QPCT;CXCR2;CYSTM1;PTX3;S100A11;TLR2 | |
neutrophil-mediated immunity | (GO:0002446) | 0.0000001009 | CDA;TNFAIP6;MME;FPR1;CXCL1;CXCR1;ALOX5;QPCT;CXCR2;CYSTM1;PTX3;S100A11;TLR2 | |
inflammatory response | (GO:0006954) | 0.000001012 | TNFAIP6;IL1B;PTGER2;CXCR2;FPR1;PIK3CD;CXCL1;PTX3;NOD2 | |
cytokine-mediated signaling pathway | (GO:0019221) | 0.0000113203 | IL1RN;IRAK2;IL1B;ALOX5;FPR1;PIK3CD;CXCL1;NOD2;XAF1;JUNB;IFIT2;BCL2L1 | |
Cellular components | tertiary granule lumen | (GO:1904724) | 0.00000322 | CDA;TNFAIP6;QPCT;CXCL1;PTX3 |
tertiary granule | (GO:0070820) | 0.00000540 | CDA;TNFAIP6;QPCT;FPR1;CXCL1;CYSTM1;PTX3 | |
ficolin-1-rich granule | (GO:0101002) | 0.001014794 | CDA;TNFAIP6;ALOX5;QPCT;FPR1 | |
ficolin-1-rich granule lumen | (GO:1904813) | 0.001721089 | CDA;TNFAIP6;ALOX5;QPCT | |
secretory granule lumen | (GO:0034774) | 0.002052377 | CDA;ALOX5;QPCT;CXCL1;PTX3;S100A11 |
GO Pathways | Adj p-Value | Genes | ||
---|---|---|---|---|
Molecular functions | ATP-dependent helicase activity | (GO:0008026) | 0.003438361 | MCM7;DDX51;DDX52 |
RNA polymerase II transcription-factor binding | (GO:0001085) | 0.009156092 | EOMES;STAT3;CTNNB1 | |
RNA polymerase II activating transcription-factor binding | (GO:0001102) | 0.012116708 | EOMES;CTNNB1 | |
inorganic anion transmembrane transporter activity | (GO:0015103) | 0.012614773 | SLC22A4;SLC1A1 | |
small GTPase binding | (GO:0031267) | 0.021109349 | ACAP1;FLNA | |
Biological Pathways | cardiolipin biosynthetic process | (GO:0032049) | 3.43 × 10−4 0.000343 | PGS1;PLA2G6 |
phosphatidylglycerol biosynthetic process | (GO:0006655) | 5.49 × 10−4 0.000549 | PGS1;PLA2G6 | |
thyroid-hormone generation | (GO:0006590) | 5.49 × 10−4 0.000549 | DUOX1;DIDO1 | |
cardiolipin metabolic process | (GO:0032048) | 9.45 × 10−4 0.000945 | PGS1;PLA2G6 | |
cytoplasmic sequestering of protein | (GO:0051220) | 0.00126624 | MXI1;FLNA | |
Cellular functions | nucleolus | (GO:0005730) | 0.010004394 | C1D;MXI1;FLNA;DDX51;RGS12;DDX52;PHLDA1 |
RNA polymerase II transcription-factor complex | (GO:0090575) | 0.015449845 | MXI1;STAT3;CTNNB1 | |
tertiary granule lumen | (GO:1904724) | 0.016344963 | CDA;CXCL1 | |
tertiary granule | (GO:0070820) | 0.020605435 | CDA;CXCL1;CD59 | |
THO complex part of transcription export complex | (GO:0000445) | 0.021114315 | THOC3 |
GEO Accession | Sample Type | PRDM2 | CXCL1 | PHLDA1 | DIDO1 | CDA |
---|---|---|---|---|---|---|
GSE14922 | Control vs. cortisol secreting adenoma | Down regulated | Down regulated | Down regulated | Up regulated | Up regulated |
GSE109857 | Control vs. glioma | Up regulated | Down regulated | Down regulated | Down regulated | Down regulated |
GSE114852 | Control vs. depression | absent | Down regulated | Down regulated | Up regulated | Down regulated |
GSE32280 | Control vs. depression | Up regulated | Down regulated | Down regulated | Down regulated | Up regulated |
GSE58430 | Control vs. depression | Down regulated | Down regulated | Up regulated | Down regulated | Up regulated |
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Bhadra, S.; Chen, S.; Liu, C. Analysis of Differentially Expressed Genes That Aggravate Metabolic Diseases in Depression. Life 2021, 11, 1203. https://doi.org/10.3390/life11111203
Bhadra S, Chen S, Liu C. Analysis of Differentially Expressed Genes That Aggravate Metabolic Diseases in Depression. Life. 2021; 11(11):1203. https://doi.org/10.3390/life11111203
Chicago/Turabian StyleBhadra, Sukanta, Siyu Chen, and Chang Liu. 2021. "Analysis of Differentially Expressed Genes That Aggravate Metabolic Diseases in Depression" Life 11, no. 11: 1203. https://doi.org/10.3390/life11111203