Determination of Genes Related to Uveitis by Utilization of the Random Walk with Restart Algorithm on a Protein–Protein Interaction Network
Abstract
:1. Introduction
2. Results and Discussion
2.1. Results of Testing Random Walk with Restart (RWR)-Based Method
2.2. RWR Genes
2.3. Candidate Genes
2.4. Analysis of Novel Genes
2.4.1. Immune System Regulation Genes
2.4.2. Transcription Associated Genes
2.4.3. Cell Adhesion and Signal Transduction Related Genes
2.5. Comparison of Other Methods
3. Materials and Methods
3.1. Materials
3.2. Protein-protein Interaction (PPI) Network
3.3. RWR-Based Method
3.3.1. Searching Possible Genes Using the RWR Algorithm
3.3.2. Excluding False Discoveries Using the Permutation Test
3.3.3. Selection of Core Genes by Associations with Validated Genes
3.4. Methods for Testing RWR-Based Method
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Index of Part | Recall | Precision | F1-Measure |
---|---|---|---|
1 | 0.172 | 0.089 | 0.118 |
2 | 0.172 | 0.088 | 0.116 |
3 | 0.379 | 0.177 | 0.242 |
4 | 0.310 | 0.141 | 0.194 |
5 | 0.400 | 0.211 | 0.276 |
Mean | 0.287 | 0.141 | 0.189 |
Ensembl ID | Gene Symbol | Description | Probability | p-Value | MIS | MFS |
---|---|---|---|---|---|---|
ENSP00000351671 b | CCL20 | C-C motif chemokine ligand 20 | 1.65 × 10−4 | <0.001 | 999 | 0.841 |
ENSP00000250151 b | CCL4 | C-C motif chemokine ligand 4 | 1.64 × 10−4 | <0.001 | 994 | 0.820 |
ENSP00000326432 c | CCR8 | C-C motif chemokine receptor 8 | 8.90 × 10−5 | <0.001 | 951 | 0.816 |
ENSP00000313419 b | CD19 | CD19 molecule | 2.15 × 10−4 | <0.001 | 947 | 0.837 |
ENSP00000320084 c | CD276 | CD276 molecule | 1.91 × 10−4 | <0.001 | 955 | 0.823 |
ENSP00000359663 b | CD40LG | CD40 ligand | 1.97 × 10−4 | <0.001 | 999 | 0.839 |
ENSP00000264246 b | CD80 | CD80 molecule | 2.18 × 10−4 | <0.001 | 999 | 0.820 |
ENSP00000283635 c | CD8A | CD8a molecule | 1.91 × 10−4 | <0.001 | 990 | 0.815 |
ENSP00000296871 c | CSF2 | Colony stimulating factor 2 | 2.71 × 10−4 | <0.001 | 992 | 0.875 |
ENSP00000225474 c | CSF3 | Colony stimulating factor 3 | 1.55 × 10−4 | <0.001 | 916 | 0.829 |
ENSP00000379110 b | CXCL1 | C-X-C motif chemokine ligand 1 | 1.69 × 10−4 | <0.001 | 973 | 0.827 |
ENSP00000306884 b | CXCL11 | C-X-C motif chemokine ligand 11 | 1.28 × 10−4 | <0.001 | 999 | 0.818 |
ENSP00000286758 b | CXCL13 | C-X-C motif chemokine ligand 13 | 1.49 × 10−4 | <0.001 | 986 | 0.806 |
ENSP00000293778 b | CXCL16 | C-X-C motif chemokine ligand 16 | 1.02 × 10−4 | <0.001 | 952 | 0.800 |
ENSP00000296027 b | CXCL5 | C-X-C motif chemokine ligand 5 | 1.11 × 10−4 | <0.001 | 958 | 0.811 |
ENSP00000354901 b | CXCL9 | C-X-C motif chemokine ligand 9 | 2.13 × 10−4 | <0.001 | 999 | 0.883 |
ENSP00000295683 c | CXCR1 | C-X-C motif chemokine receptor 1 | 8.67 × 10−5 | <0.001 | 999 | 0.833 |
ENSP00000319635 b | CXCR2 | C-X-C motif chemokine receptor 2 | 1.02 × 10−4 | <0.001 | 999 | 0.851 |
ENSP00000229239 c | GAPDH | Glyceraldehyde-3-phosphate dehydrogenase | 2.12 × 10−4 | <0.001 | 922 | 0.824 |
ENSP00000216341 c | GZMB | Granzyme B | 2.46 × 10−4 | <0.001 | 991 | 0.829 |
ENSP00000364114 c | HLA-DRB5 | Major histocompatibility complex, class II, DR β 5 | 2.27 × 10−4 | <0.001 | 948 | 0.822 |
ENSP00000304915 a | IL13 | Interleukin 13 | 1.31 × 10−4 | <0.001 | 999 | 0.813 |
ENSP00000296545 b | IL15 | Interleukin 15 | 1.85 × 10−4 | <0.001 | 946 | 0.806 |
ENSP00000263339 b | IL1A | Interleukin 1 α | 1.82 × 10−4 | <0.001 | 996 | 0.820 |
ENSP00000263341 b | IL1B | Interleukin 1 β | 3.58 × 10−4 | <0.001 | 999 | 0.873 |
ENSP00000259206 a | IL1RN | Interleukin 1 receptor antagonist | 1.68 × 10−4 | <0.001 | 999 | 0.836 |
ENSP00000228534 b | IL23A | Interleukin 23 subunit Α | 2.87 × 10−4 | <0.001 | 998 | 0.844 |
ENSP00000369293 b | IL2RA | Interleukin 2 receptor subunit Α | 2.46 × 10−4 | <0.001 | 999 | 0.866 |
ENSP00000274520 c | IL9 | Interleukin 9 | 1.27 × 10−4 | <0.001 | 965 | 0.806 |
ENSP00000360266 b | JUN | Jun proto-oncogene, AP-1 transcription factor subunit | 3.22 × 10−4 | <0.001 | 999 | 0.831 |
ENSP00000361405 b | MMP9 | Matrix metallopeptidase 9 | 1.70 × 10−4 | <0.001 | 971 | 0.833 |
ENSP00000379625 a | MYD88 | Myeloid differentiation primary response 88 | 1.82 × 10−4 | <0.001 | 999 | 0.882 |
ENSP00000356346 c | PTPRC | Protein tyrosine phosphatase, receptor type C | 2.18 × 10−4 | <0.001 | 994 | 0.826 |
ENSP00000331736 c | SELE | Selectin E | 1.46 × 10−4 | <0.001 | 978 | 0.830 |
ENSP00000354394 b | STAT1 | Signal transducer and activator of transcription 1 | 2.63 × 10−4 | <0.001 | 999 | 0.852 |
ENSP00000300134 b | STAT6 | Signal transducer and activator of transcription 6 | 1.77 × 10−4 | <0.001 | 999 | 0.804 |
ENSP00000221930 a | TGFB1 | Transforming growth factor β 1 | 2.90 × 10−4 | <0.001 | 997 | 0.832 |
ENSP00000416330 c | TGFBI | Transforming growth factor β induced | 1.91 × 10−4 | <0.001 | 917 | 0.813 |
ENSP00000260010 b | TLR2 | Toll like receptor 2 | 2.25 × 10−4 | <0.001 | 968 | 0.888 |
ENSP00000370034 b | TLR7 | Toll like receptor 7 | 1.26 × 10−4 | <0.001 | 926 | 0.819 |
ENSP00000353874 b | TLR9 | Toll like receptor 9 | 1.55 × 10−4 | <0.001 | 958 | 0.854 |
ENSP00000294728 b | VCAM1 | Vascular cell adhesion molecule 1 | 2.23 × 10−4 | <0.001 | 968 | 0.882 |
ENSP00000292174 c | CXCR5 | C-X-C motif chemokine receptor 5 | 1.14 × 10−4 | 0.001 | 976 | 0.820 |
ENSP00000343204 a | JAK1 | Janus kinase 1 | 1.21 × 10−4 | 0.001 | 999 | 0.818 |
ENSP00000162749 b | TNFRSF1A | TNF Receptor superfamily member 1A | 2.30 × 10−4 | 0.001 | 999 | 0.826 |
ENSP00000304414 c | CXCR6 | C-X-C motif chemokine receptor 6 | 9.27 × 10−5 | 0.002 | 964 | 0.803 |
ENSP00000296795 a | TLR3 | Toll like receptor 3 | 1.58 × 10−4 | 0.002 | 966 | 0.858 |
ENSP00000231454 c | IL5 | Interleukin 5 | 1.13 × 10−4 | 0.004 | 991 | 0.803 |
ENSP00000222823 a | NOD1 | Nucleotide binding oligomerization domain containing 1 | 7.72 × 10−5 | 0.004 | 991 | 0.866 |
ENSP00000231449 b | IL4 | Interleukin 4 | 2.55 × 10−4 | 0.005 | 999 | 0.852 |
ENSP00000356438 a | PTGS2 | Prostaglandin-endoperoxide synthase 2 | 1.92 × 10−4 | 0.009 | 972 | 0.864 |
ENSP00000219244 b | CCL17 | C-C motif chemokine ligand 17 | 1.20 × 10−4 | 0.01 | 984 | 0.808 |
ENSP00000351273 b | CASP8 | Caspase 8 | 9.66 × 10−5 | 0.027 | 999 | 0.821 |
ENSP00000353483 c | MAPK8 | Mitogen-activated protein kinase 8 | 1.03 × 10−4 | 0.034 | 925 | 0.847 |
ENSP00000228280 c | KITLG | KIT ligand | 9.60 × 10−5 | 0.039 | 958 | 0.810 |
ENSP00000238682 c | TGFB3 | Transforming growth factor β 3 | 5.37 × 10−5 | 0.049 | 961 | 0.850 |
Index of Part | RWR-Based Method | GBA-Based Method | |||||
---|---|---|---|---|---|---|---|
Recall | Precision | F1-Measure | Best Value of k | Recall | Precision | F1-Measure | |
1 | 0.172 | 0.089 | 0.118 | 1 | 0.207 | 0.061 | 0.094 |
2 | 0.172 | 0.088 | 0.116 | 1 | 0.207 | 0.059 | 0.092 |
3 | 0.379 | 0.177 | 0.242 | 3 | 0.345 | 0.039 | 0.069 |
4 | 0.310 | 0.141 | 0.194 | 1 | 0.172 | 0.052 | 0.079 |
5 | 0.400 | 0.211 | 0.276 | 3 | 0.500 | 0.061 | 0.109 |
RWR-Based Method |
---|
Input: Ensembl IDs of uveitis-related genes, a PPI network Output: A number of putative uveitis-related genes |
|
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Lu, S.; Yan, Y.; Li, Z.; Chen, L.; Yang, J.; Zhang, Y.; Wang, S.; Liu, L. Determination of Genes Related to Uveitis by Utilization of the Random Walk with Restart Algorithm on a Protein–Protein Interaction Network. Int. J. Mol. Sci. 2017, 18, 1045. https://doi.org/10.3390/ijms18051045
Lu S, Yan Y, Li Z, Chen L, Yang J, Zhang Y, Wang S, Liu L. Determination of Genes Related to Uveitis by Utilization of the Random Walk with Restart Algorithm on a Protein–Protein Interaction Network. International Journal of Molecular Sciences. 2017; 18(5):1045. https://doi.org/10.3390/ijms18051045
Chicago/Turabian StyleLu, Shiheng, Yan Yan, Zhen Li, Lei Chen, Jing Yang, Yuhang Zhang, Shaopeng Wang, and Lin Liu. 2017. "Determination of Genes Related to Uveitis by Utilization of the Random Walk with Restart Algorithm on a Protein–Protein Interaction Network" International Journal of Molecular Sciences 18, no. 5: 1045. https://doi.org/10.3390/ijms18051045