Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis
Abstract
:1. Introduction
2. Method
2.1. Data Collection and Quality Check
2.2. Dataset Preprocessing by Seurat
2.3. Dimensionality Reduction and Cluster Identification
2.4. Determination of Copy Number Variations (CNVs)
2.5. Differential Gene Expression and Functional Annotation
2.6. Network Analysis
2.7. Monocle Pseudotime Trajectory Reconstruction and Analysis
3. Results
3.1. Cell Clusters and Tumor Heterogeneity in GBM
3.1.1. Cell Type Identifications of the Clusters
3.1.2. Marker Genes in Each Cluster
3.2. Differentially Expressed Genes (DEGs) between Tumor and Periphery Cells
3.3. Tumor Heterogeneity with CNV Profiles
3.4. Pathway/Function Enrichment Analysis for DEGs
3.5. The Transition of Microglial Immune Cells to Neoplastic Cells: Pseudotime Analysis
3.6. Protein–Protein Interaction Networks (PPI) and Tissue-Specific Co-Expression Networks for DEGs
3.6.1. PPI Network in DEGs
3.6.2. Tissue-Specific Co-Expression Network of DEGs
4. Discussion
Comparison with Other Related Works
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Chromosome | Gene Symbol | Start Position | End Position | Description | Expression |
---|---|---|---|---|---|
Chr 10 | VIM | 17228241 | 17237593 | Vimentin | UP |
HTRA1 | 1.22 × 108 | 1.23 × 108 | HtrA serine peptidase 1 | DOWN | |
SCD * | 1 × 108 | 1 × 108 | Stearoyl-CoA desaturase | DOWN | |
PSAP | 71816298 | 71851251 | Prosaposin | DOWN | |
EGR2 | 62811996 | 62819167 | Early growth response 2 | DOWN | |
PIP4K2A | 22534854 | 22714578 | Phosphatidylinositol-5-phosphate 4-kinase type 2 α | DOWN | |
SRGN | 69057533 | 69104811 | Serglycin | - | |
PPA1 | 70202831 | 70233429 | Inorganic pyrophosphatase 1 | DOWN | |
OPALIN * | 96343221 | 96359002 | Oligodendrocytic myelin paranodal and inner loop protein | NI | |
PHYHIPL * | 59175872 | 59247770 | Phytanoyl-CoA 2-hydroxylase interacting protein like | DOWN | |
Chr 7 | ANLN | 36389806 | 36453791 | Anillin actin binding protein | UP |
SRI * | 88205118 | 88226993 | Sorcin | UP | |
PON2 | 95404863 | 95435329 | Paraoxonase 2 | UP | |
ITGB8 | 20330702 | 20415754 | Integrin subunit β 8 | UP | |
PTN | 1.37 × 108 | 1.37 × 108 | Pleiotrophin | UP | |
CAV1 | 1.17 × 108 | 1.17 × 108 | Caveolin 1 | NI | |
NPTX2 * | 98617297 | 98629868 | Neuronal pentraxin 2 | DOWN | |
PTPRZ1 | 1.22 × 108 | 1.22 × 108 | Protein tyrosine phosphatase receptor type Z1 | DOWN | |
MEST * | 1.30 × 108 | 1.31 × 108 | Mesoderm specific transcript | UP | |
RARRES2 * | 1.50 × 108 | 1.50 × 108 | Retinoic acid receptor responder 2 | NI | |
SEPTIN7 * | 35800932 | 35907105 | Septin 7 | NI | |
CALD1 | 1.35 × 108 | 1.35 × 108 | Caldesmon 1 | UP | |
GNAI1 | 80133955 | 80219402 | G protein subunit α I1 | - | |
RAPGEF5 | 22118238 | 22357144 | Rap guanine nucleotide exchange factor 5 | UP | |
EGFR | 55019021 | 55256620 | Epidermal growth factor receptor | DOWN | |
IGFBP3 | 45912245 | 45921874 | Insulin-like growth factor binding protein 3 | NI | |
COL1A2 | 94394561 | 94431232 | Collagen type I α 2 chain | DOWN | |
GPR37 | 1.25E+08 | 1.25 × 108 | G protein-coupled receptor 37 | NI | |
NDUFA4 | 10931951 | 10940256 | NDUFA4 mitochondrial complex associated | UP | |
GRM3 | 86643914 | 86864884 | Glutamate metabotropic receptor 3 | NI | |
Chr 13 | TSC22D1 | 44432143 | 44577147 | TSC22 domain family member 1 | - |
HSPH1 * | 31134974 | 31162388 | Heat shock protein family H (Hsp110) member 1 | NI | |
COL4A2 | 1.10E+08 | 1.11 × 108 | Collagen type IV α 2 chain | NI | |
SLAIN1 * | 77697854 | 77764242 | SLAIN motif family member 1 | DOWN | |
AMER2 * | 25161684 | 25172288 | APC membrane recruitment protein 2 | DOWN | |
GPR183 * | 99294530 | 99307405 | G protein-coupled receptor 183 | DOWN | |
PCDH9 * | 66302834 | 67230445 | Protocadherin 9 | DOWN | |
COL4A1 | 1.10 × 108 | 1.10 × 108 | Collagen type IV α 1 chain | NI | |
HMGB1 | 30456704 | 30617597 | High mobility group box 1 | NI | |
Chr6 | TNF | 31575565 | 31578336 | Tumor necrosis factor | UP |
F13A1 * | 6144084 | 6320662 | Coagulation factor XIII A chain | DOWN | |
MYO6 | 75749203 | 75919537 | Myosin VI | DOWN | |
AKAP12 * | 1.51 × 108 | 151358559 | A-kinase anchoring protein 12 | DOWN | |
CD109 * | 73696203 | 73828313 | CD109 molecule | UP | |
SLC16A10 | 1.11 × 108 | 111231194 | Solute carrier family 16-member 10 | DOWN | |
UST * | 1.49 × 108 | 149076990 | Uronyl 2-sulfotransferase | DOWN | |
IPCEF1 * | 1.54 × 108 | 154356803 | Interaction protein for cytohesin exchange factors 1 | UP | |
TSPYL4 * | 1.16 × 108 | 116254075 | TSPY like 4 | DOWN | |
SELPLG * | 1.09 × 108 | 108633894 | Selectin P ligand | UP | |
ENO2 | 6914580 | 6923697 | Enolase 2 | NI | |
DUSP6 | 89347235 | 89352501 | Dual specificity phosphatase 6 | UP | |
Chr 12 | C3AR1 * | 8056844 | 8066359 | Complement C3a receptor 1 | DOWN |
FAIM2 * | 49866896 | 49903900 | Fas apoptotic inhibitory molecule 2 | UP | |
FMNL3 | 49636499 | 49707405 | Formin like 3 | DOWN | |
NAV3 | 77571856 | 78213010 | Neuron navigator 3 | DOWN | |
GPN3 | 1.1 × 108 | 110468721 | GPN-loop GTPase 3 | DOWN | |
PRPF40B | 49622717 | 49645129 | Pre-mRNA processing factor 40 homolog B | NI | |
LGALS3 | 55129252 | 55145430 | Complement C3a receptor 1 | UP | |
NDRG2 | 21016763 | 21070872 | Fas apoptotic inhibitory molecule 2 | DOWN | |
HSPA2 | 64535905 | 64543237 | Formin like 3 | DOWN | |
RTN1 | 59595976 | 59871288 | Neuron navigator 3 | UP | |
SLC22A17 | 23346304 | 23354991 | GPN-loop GTPase 3 | UP | |
PLD4 | 1.05 × 108 | 104937789 | Pre-mRNA processing factor 40 homolog B | UP | |
Chr 17 | CCL2 | 34255285 | 34257203 | C–C motif chemokine ligand 2 | UP |
SOX9 | 72121020 | 72126416 | SRY-box transcription factor 9 | DOWN | |
CCL3 | 36088256 | 36090143 | C–C motif chemokine ligand 3 | UP | |
CCL4 | 36103827 | 36105614 | C–C motif chemokine ligand 4 | UP | |
ABCC3 | 50634881 | 50692253 | ATP-binding cassette subfamily C member 3 | UP | |
CCL4L2 | 36211063 | 36212873 | C–C motif chemokine ligand 4 like 2 | UP | |
Chr 22 | MIF | 23894383 | 23895223 | Macrophage migration inhibitory factor | DOWN |
LGALS1 | 37675636 | 37679802 | Galectin 1 | DOWN | |
PDGFB | 39223359 | 39244982 | Platelet-derived growth factor subunit B | DOWN | |
TNFRSF13C * | 41922032 | 41926806 | TNF receptor superfamily member 13C | DOWN | |
CECR2 | 17359949 | 17558151 | CECR2 histone acetyl-lysine reader | DOWN |
Analysis Type | Novel Genes | Total |
---|---|---|
Filtered DEGs | DHRS9, IPCEF1, TNR, MEGF11, EDIL3, PDZD2, ATP1A2, PDGFRA, LINC00632, AC243829.4, AC024909.2, MEG3, CHI3L1, FN1, IGFBP2, TNC, FCGBP, CYR61, F13A1, ANXA2, AC006064.4, ANXA1, CH25H and MIF-AS1 | 24 |
CNV detection | SCD, OPALIN, PHYHIPL, PSAP, SRI, NPTX2, MEST, RARRES2, SEPTIN7, HSPH1, SLAIN1, AMER2, GPR183, PCDH9, F13A1, AKAP12, CD109, UST, IPCEF1, TSPYL4, SELPLG, C3AR1, FAIM2 and TNFRSF13C | 24 |
Network construction | B3GNT5, SELPLG and TPI1 | 3 |
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Yesudhas, D.; Dharshini, S.A.P.; Taguchi, Y.-h.; Gromiha, M.M. Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis. Genes 2022, 13, 428. https://doi.org/10.3390/genes13030428
Yesudhas D, Dharshini SAP, Taguchi Y-h, Gromiha MM. Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis. Genes. 2022; 13(3):428. https://doi.org/10.3390/genes13030428
Chicago/Turabian StyleYesudhas, Dhanusha, S. Akila Parvathy Dharshini, Y-h. Taguchi, and M. Michael Gromiha. 2022. "Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis" Genes 13, no. 3: 428. https://doi.org/10.3390/genes13030428
APA StyleYesudhas, D., Dharshini, S. A. P., Taguchi, Y.-h., & Gromiha, M. M. (2022). Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis. Genes, 13(3), 428. https://doi.org/10.3390/genes13030428