Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Collection
2.2. Regulatory Network Construction
2.3. Analyzing of the TFsand Hub Regulators in the Networks
2.4. Network Visualization and Comparison
3. Results
3.1. Characterize Gene Regulatory Networks of Key Immune Cells Associated with Cancer Immunotherapy
3.2. Melanoma Cells Shut Down Many Network Activities of the CD8 T Cells
4. Discussion
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Cell Type | Numbers of Annotated Genes | Number of Genes that Are Unique to Each Cell Type | Numbers of Receptors | Numbers of Receptor that Are Unique to Each Cell Type | Numbers of TFs | Numbers of TFs that Are Unique to Each Cell Type |
---|---|---|---|---|---|---|
B | 9058 | 396 | 250 | 12 | 168 | 14 |
CD4 | 9128 | 68 | 280 | 1 | 164 | 2 |
CD8 | 8997 | 71 | 269 | 3 | 161 | 1 |
DC | 12,459 | 1255 | 480 | 69 | 254 | 34 |
NK | 7186 | 39 | 197 | 0 | 129 | 1 |
Regulatory T | 8309 | 72 | 238 | 1 | 143 | 1 |
Thelper1 | 7533 | 41 | 229 | 4 | 119 | 1 |
Thelper2 | 8606 | 36 | 257 | 0 | 160 | 1 |
Thelper17 | 9947 | 3903 | 341 | 74 | 217 | 84 |
B-Cell | |
Pathway Name | p-Value |
TPO Signaling Pathway | 1.95 × 10−4 |
IL-2 Receptor Beta Chain in T Cell Activation | 4.45 × 10−5 |
PDGF Signaling Pathway | 1.16 × 10−3 |
Role of Calcineurin-dependent NFAT (Nuclear factor of activated T-cells) signaling in lymphocytes | 1.23792 × 10−4 |
Phosphoinositides and their downstream targets | 5.69 × 10−4 |
CD4 | |
Pathway Name | p-Value |
ErbB1 downstream signaling | 3.10 × 10−10 |
mTOR signaling pathway | 6.80 × 10−9 |
Ras Pathway | 6.80 × 10−9 |
IL2-mediated signaling events | 3.17 × 10−8 |
PDGFR (Platelet-derived growth factor receptors)-beta signaling pathway | 1.13 × 10−7 |
CD8 | |
Pathway Name | p-Value |
FoxO family signaling | 1.25 × 10−8 |
Fanconi anemia pathway | 3.60 × 10−6 |
E2F transcription factor network | 4.26 × 10−6 |
Dendritic Cell | |
Pathway Name | p-Value |
BCR signaling pathway | 0.81 × 10−8 |
CCKR signaling map | 6.83 × 10−7 |
TCR signaling in naive CD4+ T cells | 1.455 × 10−6 |
CXCR4-mediated signaling events | 1.66 × 10−6 |
FoxO family signaling | 4.05 × 10−6 |
Class I PI3K signaling events | 4.05 × 10−6 |
NK cells | |
Pathway Name | p-Value |
ATR signaling pathway | 3.25 × 10−8 |
FoxO family signaling | 1.97 × 10−7 |
CCKR (cholecystokinin receptor) signaling map signal transduction | 4.29 × 10−7 |
Regulatory T cell | |
Pathway Name | p-Value |
ATR signaling pathway | 6.72 × 10−7 |
Cell Type | Computational Method Employed | Key_Regulators |
---|---|---|
B | Network-analysis | SP1, EGR1, TFDP1, SP2, SP4, MAZ, SP3, THAP1, KLF16, TBX15, WT1, KLF4, ZN148, EGR4, TBX1, PLAG1, KLF6, ZN639, ZFX, KLF14 |
PageRank algorithm | SP1, EGR1, TFDP1, SP4, SP2, MAZ, SP3, THAP1, KLF16, WT1, TBX15, KLF4, ZN148, EGR4, TBX1, ZFX, KLF6, ZN639, ELF2, PLAG1 | |
CD4 | Network-analysis | SP1, EGR1, TFDP1, SP2, MAZ, SP4, SP3, THAP1, KLF16, TBX15, WT1, EGR4, KLF4, ZN148, TBX1, KLF6, ZN639, PLAG1, ZFX, ELF2, |
PageRank algorithm | SP1, EGR1, TFDP1, MAZ, SP2, SP4, SP3, THAP1, KLF16, TBX15, WT1, EGR4, KLF4, ZN148, TBX1, KLF6ZN639, ZFX, PLAG1, ELF2 | |
CD8 | Network-analysis | SP1, EGR1, TFDP1, SP2, MAZ, SP4, SP3, THAP1, KLF16, WT1, TBX15, EGR4, KLF4, ZN148, KLF6, TBX1, PLAG1, ZN639, ZFX, KLF14 |
PageRank algorithm | SP1, EGR1, TFDP1, SP2, SP4, MAZ, SP3, THAP1, KLF16, WT1, TBX15, EGR4, KLF4, ZN148, KLF6, TBX1, ZN639, PLAG1, ZFX, ELF2 | |
DC | Network-analysis | SP1, EGR1, TFDP1, SP2, SP4, MAZ, SP3, THAP1, KLF16, TBX15, WT1, EGR4, ZN148, TBX1, KLF6, PLAG1, KLF4, ZFX, ZN639, AP2D |
PageRank algorithm | SP1, EGR1, TFDP1, SP2, SP4, MAZ, SP3, THAP1, KLF16, TBX15, WT1, EGR4, TBX1, ZN148, KLF6, KLF4, PLAG1, ZN639, ZFX, ELF2 | |
NK | Network-analysis | SP1, EGR1, TFDP1, SP2, MAZ, SP4, SP3, THAP1, KLF16, TBX15, WT1, KLF4, EGR4, ZN148, TBX1, KLF6, ELF2, ZN639, PLAG1, ZFX |
PageRank algorithm | SP1, EGR1, TFDP1, MAZ, SP2, SP4, SP3, THAP1, KLF16, TBX15, WT1, KLF4, EGR4, TBX1, ZN639, ZN148, KLF6, ELF2, ZFX, PLAG1 | |
Regulatory T | Network-analysis | SP1, EGR1, TFDP1, SP2, MAZ, SP4, SP3, THAP1, KLF16, TBX15, WT1, KLF4, ZN148, EGR4, TBX1, KLF6, PLAG1, ZN639, ELF2, ZFX |
PageRank algorithm | SP1, EGR1, TFDP1, SP2, SP4, MAZ, SP3, THAP1, KLF16, TBX15, WT1, KLF4, EGR4, ZN148, TBX1, ZN639, KLF6, ELF2, ZFX, PLAG1 | |
Thelper17 | Network-analysis | SP1, EGR1, MAZ, SP2, TFDP1, SP4, SP3, TBX15, PLAG1, KLF16, TBX1, PAX5, PURA, ZN148, THAP1, WT1, KLF15, MNT, ZFX, AP2D |
PageRank algorithm | SP1, EGR1, MAZ, SP2, TFDP1, SP4, SP3, TBX15, PLAG1, KLF16, TBX1, PAX5, PURA, ZN148, THAP1, MNT, WT1, KLF15, ZFX, AP2D | |
Thelper1 | Network-analysis | SP1, EGR1, TFDP1, SP2, MAZ, SP4, SP3, THAP1, KLF16, TBX15, WT1, KLF4, ZN148, TBX1, ELF2, KLF6, EGR4, ZN639, KLF14, ZFX |
PageRank algorithm | SP1, EGR1, TFDP1, SP2, MAZ, SP4, SP3, THAP1, KLF16, TBX15, WT1, KLF4, ELF2, ZN148, ZN639, KLF6, EGR4, TBX1, ZFX, KLF14 | |
Thelper2 | Network-analysis | SP1, EGR1, TFDP1, SP2, SP4, MAZ, SP3, THAP1, KLF16, WT1, TBX15, KLF4, EGR4, ZN148, KLF6, TBX1, ZN639, KLF14, ELF2, PLAG1 |
PageRank algorithm | SP1, EGR1, TFDP1, SP2, SP4, MAZ, SP3, THAP1, KLF16, WT1, TBX15, KLF4, EGR4, ZN639, KLF6, ZN148, TBX1, ELF2, ZFX, KLF14 |
Cell Type | Name | p-Value |
---|---|---|
HCM vs PD1lo | Calcineurin-regulated NFAT (Nuclear factor of activated T-cells) -dependent transcription in lymphocytes | 1.443 × 10−12 |
IL2 signaling events mediated by STAT5 | 1.34 × 10−12 | |
Downstream signaling in naive CD8+ T cells | 1.036 × 10−8 | |
IL12-mediated signaling events | 2.724 × 10−8 | |
FoxO family signaling | 3.688 × 10−8 | |
HCM vs PD1hi | Calcineurin-regulated NFAT-dependent transcription in lymphocytes | 9.083 × 10−13 |
IL2 signaling events mediated by STAT5 | 4.072 × 10−11 | |
GMCSF-mediated signaling events | 8.323 × 10−9 | |
IL2-mediated signaling events | 2.378 × 10−8 | |
AP-1 transcription factor network | 5.012 × 10−7 | |
HEM vs PD1lo | Calcineurin-regulated NFAT-dependent transcription in lymphocytes | 6.401 × 10−16 |
IL2 signaling events mediated by STAT5 | 1.157 × 10−12 | |
Downstream signaling in naive CD8+ T cells | 6.909 × 10−11 | |
IL12-mediated signaling events | 4.682 × 10−10 | |
AP-1 transcription factor network | 2.142 × 10−8 | |
HEM vs PD1hi | Calcineurin-regulated NFAT-dependent transcription in lymphocytes | 2.304 × 10−14 |
AP-1 transcription factor network | 1.869 × 10−9 | |
IL2 signaling events mediated by STAT5 | 1.363 × 10−10 | |
IL2-mediated signaling events | 4.521 × 10−8 | |
IL12-mediated signaling events | 1.329 × 10−7 | |
HN vs PD1lo | Validated targets of C-MYC transcriptional activation | 5.009 × 10−7 |
Glucocorticoid receptor regulatory network | 5.60 × 10−5 | |
FoxO family signaling | 4.64 × 10−5 | |
Role of Calcineurin-dependent NFAT signaling in lymphocytes | 9.98 × 10−5 | |
IL12-mediated signaling events | 3.25 × 10−4 | |
HN vs PD1hi | Calcineurin-regulated NFAT-dependent transcription in lymphocytes | 8.443 × 10−8 |
AP-1 transcription factor network | 3.14 × 10−6 | |
IL2 signaling events | 6.686 × 10−7 | |
IL5-mediated signaling events | 2.65 × 10−5 | |
IL2-mediated signaling events | 4.72 × 10−5 | |
PD1hi vs PD1lo | IL12 signaling mediated by STAT4 | 5.04 × 10−4 |
IL12-mediated signaling events | 3.60 × 10−3 | |
TCR signaling in naive CD4+ T cells | 4.00 × 10−3 | |
Glucocorticoid receptor regulatory network | 8.30 × 10−3 | |
ATF-2 transcription factor network | 7.50 × 10−2 |
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Han, P.; Gopalakrishnan, C.; Yu, H.; Wang, E. Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer. Genes 2017, 8, 308. https://doi.org/10.3390/genes8110308
Han P, Gopalakrishnan C, Yu H, Wang E. Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer. Genes. 2017; 8(11):308. https://doi.org/10.3390/genes8110308
Chicago/Turabian StyleHan, Pengyong, Chandrasekhar Gopalakrishnan, Haiquan Yu, and Edwin Wang. 2017. "Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer" Genes 8, no. 11: 308. https://doi.org/10.3390/genes8110308
APA StyleHan, P., Gopalakrishnan, C., Yu, H., & Wang, E. (2017). Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer. Genes, 8(11), 308. https://doi.org/10.3390/genes8110308