The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Implementation and Software
2.2. Sample Collection and Ethics
2.3. Data Sources for Cellular mRNA and miRNA Expression Levels, Patient Cohort Composition, and Analysis Workflow
2.4. Data Sources for Viral mRNA and miRNA Expression Levels, Patient Cohort Composition, and Analysis Workflow
2.5. Data Sources for Immune Landscape Features, Patient Cohort Composition, and Analysis Workflow
2.6. Data Sources for Patient Survival, Patient Cohort Composition, and Analysis Workflow
2.7. Data Sources for DNA Methylation Levels, Patient Cohort Composition, and Analysis Workflow
2.8. Data Sources for Single-Cell Analysis, Patient Cohort Composition, and Analysis Workflow
3. Results
3.1. Differentially Expressed Gene Analysis
3.2. Correlations between Cellular and Viral Gene Expressions
3.3. The Impact of Gene Expression Levels on Overall Survival
3.4. The Correlation of Gene Expression Levels with Immune Landscape Features
3.5. Differential Probe Methylation Analysis
3.6. Single-Cell Analysis
3.7. Example Case Study
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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# of Patient Samples Analyzed | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient Subset | mRNA-seq | miRNA-seq | Cellular mRNA vs. Viral mRNA | Cellular miRNA vs. Viral mRNA | Cellular mRNA vs. Viral miRNA | Cellular miRNA vs. Viral miRNA | Immune Comparisons—Cellular mRNA | Immune Comparisons—Cellular miRNA | Immune Comparisons—Viral mRNA/miRNA | Overall Survival—Cellular mRNA | Overall Survival—Cellular miRNA | Methylation |
EBV | 30 | 29 | 26 | 25 | 29 | 30 | 30 | 29 | 26 (mRNA) 29 (miRNA) | 30 | 29 | 29 |
MSI | 73 | 59 | NA | NA | NA | NA | 73 | 59 | NA | 72 | 58 | 58 |
CIN | 223 | 203 | 223 | 201 | 220 | 199 | 202 | |||||
GS | 60 | 46 | 60 | 46 | 49 | 45 | 46 | |||||
POLE | 7 | 7 | 7 | 7 | 7 | 7 | 7 | |||||
Normal | 35 | 41 | NA | NA | NA | NA | 18 |
Immune Landscape Features * | |
---|---|
Aneuploidy score | Monocytes |
B cells memory | Neutrophils |
B cells naive | NK cells activated |
BCR evenness | NK cells resting |
BCR richness | Nonsilent mutation rate |
BCR Shannon | No. of segments |
CTA score | Plasma cells |
Dendritic cells | Proliferation |
Dendritic cells activated | Silent mutation rate |
Dendritic cells resting | SNV neoantigens |
Eosinophils | Stromal fraction |
Fraction altered | T cells CD4 memory activated |
Homologous recombination defects | T cells CD4 memory resting |
IFN gamma response | T cells CD4 Naive |
Indel neoantigens | T cells CD8 |
Intratumor heterogeneity | T cells follicular helper |
Leukocyte fraction | T cells gamma delta |
Lymphocyte infiltration signature score | T cells regulatory Tregs |
Lymphocytes | TCR evenness |
Macrophage regulation | TCR richness |
Macrophages | TCR Shannon |
Macrophages M0 | TGF beta response |
Macrophages M1 | Th1 cells |
Macrophages M2 | Th17 cells |
Mast cells | Th2 cells |
Mast cells activated | Wound healing |
Mast cells resting |
Cellular mRNAs | Cellular miRNAs | |||||
---|---|---|---|---|---|---|
Viral mRNA | # of Positive Correlations | # of Negative Correlations | # of Non-Significant Correlations | # of Positive Correlations | # of Negative Correlations | # of Non-Significant Correlations |
A73 | 0 | 4 | 20,527 | 0 | 0 | 1046 |
BALF1 | 2 | 0 | 20,529 | 0 | 0 | 1046 |
BALF2 | 2 | 1 | 20,528 | 5 | 63 | 978 |
BALF3 | 0 | 0 | 20,531 | 0 | 6 | 1040 |
BALF4 | 1105 | 1077 | 18,349 | 0 | 7 | 1039 |
BALF5 | 852 | 952 | 18,727 | 2 | 50 | 994 |
BARF0 | 1 | 0 | 20,530 | 0 | 0 | 1046 |
BARF1 | 1 | 0 | 20,530 | 0 | 1 | 1045 |
BNRF1 | 1 | 0 | 20,530 | 0 | 0 | 1046 |
EBER1 | 1008 | 1140 | 18,383 | 36 | 4 | 1006 |
EBNA-1 | 4 | 7 | 20,520 | 0 | 0 | 1046 |
LF2 | 109 | 114 | 20,308 | 0 | 0 | 1046 |
LMP2B | 0 | 0 | 20,531 | 0 | 2 | 1044 |
RPMS1 | 740 | 526 | 19,265 | 5 | 16 | 1025 |
Cellular mRNAs | Cellular miRNAs | |||||
---|---|---|---|---|---|---|
Viral mRNA | # of Positive Correlations | # of Negative Correlations | # of Non-Significant Correlations | # of Positive Correlations | # of Negative Correlations | # of Non-Significant Correlations |
ebv-miR-BART10-3p | 1351 | 4371 | 14,809 | 166 | 19 | 861 |
ebv-miR-BART11-5p | 6 | 19 | 20,506 | 5 | 2 | 1039 |
ebv-miR-BART12 | 0 | 0 | 20,531 | 77 | 0 | 969 |
ebv-miR-BART13-3p | 99 | 239 | 20,193 | 20 | 0 | 1026 |
ebv-miR-BART13-5p | 328 | 169 | 20,034 | 0 | 3 | 1043 |
ebv-miR-BART14-3p | 31 | 467 | 20,033 | 140 | 0 | 906 |
ebv-miR-BART14-5p | 391 | 1864 | 18,276 | 237 | 5 | 804 |
ebv-miR-BART15 | 939 | 2977 | 16,615 | 209 | 6 | 831 |
ebv-miR-BART1-5p | 64 | 988 | 19,479 | 13 | 0 | 1033 |
ebv-miR-BART17-3p | 519 | 2971 | 17,041 | 124 | 6 | 916 |
ebv-miR-BART17-5p | 0 | 0 | 20,531 | 1 | 0 | 1045 |
ebv-miR-BART18-3p | 315 | 212 | 20,004 | 0 | 0 | 1046 |
ebv-miR-BART19-3p | 0 | 9 | 20,522 | 23 | 0 | 1023 |
ebv-miR-BART19-5p | 706 | 3171 | 16,654 | 223 | 8 | 815 |
ebv-miR-BART20-5p | 420 | 1538 | 18,573 | 43 | 0 | 1003 |
ebv-miR-BART21-3p | 0 | 0 | 20,531 | 117 | 4 | 925 |
ebv-miR-BART22 | 891 | 3928 | 15,712 | 123 | 17 | 906 |
ebv-miR-BART2-3p | 233 | 1094 | 19,204 | 217 | 6 | 823 |
ebv-miR-BART2-5p | 506 | 3218 | 16,807 | 155 | 5 | 886 |
ebv-miR-BART3-3p | 147 | 524 | 19,860 | 71 | 0 | 975 |
ebv-miR-BART4-3p | 116 | 388 | 20,027 | 121 | 4 | 921 |
ebv-miR-BART4-5p | 241 | 1301 | 18,989 | 221 | 9 | 816 |
ebv-miR-BART5-5p | 815 | 3885 | 15,831 | 162 | 16 | 868 |
ebv-miR-BART6-3p | 606 | 2812 | 17,113 | 191 | 6 | 849 |
ebv-miR-BART6-5p | 402 | 1066 | 19,063 | 16 | 0 | 1030 |
ebv-miR-BART7-3p | 173 | 696 | 19,662 | 121 | 0 | 925 |
ebv-miR-BART7-5p | 275 | 672 | 19,584 | 166 | 2 | 878 |
ebv-miR-BART8-3p | 858 | 3550 | 16,123 | 129 | 16 | 901 |
ebv-miR-BART8-5p | 570 | 2792 | 17,169 | 187 | 7 | 852 |
ebv-miR-BART9-3p | 432 | 1766 | 18,333 | 29 | 6 | 1011 |
ebv-miR-BART9-5p | 959 | 3215 | 16,357 | 148 | 4 | 894 |
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Salnikov, M.Y.; Wang, E.; Christensen, E.; Prusinkiewicz, M.A.; Shooshtari, P.; Mymryk, J.S. The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis. Viruses 2023, 15, 853. https://doi.org/10.3390/v15040853
Salnikov MY, Wang E, Christensen E, Prusinkiewicz MA, Shooshtari P, Mymryk JS. The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis. Viruses. 2023; 15(4):853. https://doi.org/10.3390/v15040853
Chicago/Turabian StyleSalnikov, Mikhail Y., Eric Wang, Erik Christensen, Martin A. Prusinkiewicz, Parisa Shooshtari, and Joe S. Mymryk. 2023. "The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis" Viruses 15, no. 4: 853. https://doi.org/10.3390/v15040853
APA StyleSalnikov, M. Y., Wang, E., Christensen, E., Prusinkiewicz, M. A., Shooshtari, P., & Mymryk, J. S. (2023). The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis. Viruses, 15(4), 853. https://doi.org/10.3390/v15040853