Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine
Abstract
:1. Introduction
2. Materials and Methods
2.1. Clinical Study
2.2. Transcriptomics
2.2.1. RNA-Seq Experiments
2.2.2. RNA-Seq Data Processing and Analysis
2.2.3. RNA-Seq Data Availability
2.3. Metabolomics
2.3.1. Amino Acid Sample and Data Processing
2.3.2. Organic Acid Sample Experiment
2.3.3. High-Resolution LC–MS Metabolomics Experiment
2.3.4. Metabolomics Analysis
Filtering and Normalization of Metabolomics Data
Missing Value Imputation
Identification of Differentially Abundant Metabolites
Identification of Metabolomics Responses that Best Predict Adaptive Immune Response
Integration of Metabolomics and Transcriptomics Results
Data Availability
2.4. Ethical Statement
3. Results
3.1. PBMC Gene Expression Following Tularemia Vaccination Showed Increases over Time in Magnitude and Complexity with the Majority of Genes Being Down-Regulated
3.2. Tularemia Vaccine Activated PBMC Gene Expression Patterns Related to Interferon Signaling But Repressed Other Cytokine and Innate Immune Signaling Pathways Involved in Inflammation
3.3. Tularemia Vaccine Induced Gene Expression Signals Related to the Adaptive Immune Response at Day 7 and 14
3.4. Changes in Plasma Amino and Organic Acids within 2 Days after Tularemia Vaccination
3.5. Untargeted Metabolomics Revealed Changes in Energy Metabolism and Nucleotide Metabolism
3.6. Exploring Metabolite Predictors of Antibody and T Cell Responses
3.7. Significant Correlations between Genes and Metabolites and Association with Immune Responses
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Goll, J.B.; Li, S.; Edwards, J.L.; Bosinger, S.E.; Jensen, T.L.; Wang, Y.; Hooper, W.F.; Gelber, C.E.; Sanders, K.L.; Anderson, E.J.; et al. Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine. Vaccines 2020, 8, 412. https://doi.org/10.3390/vaccines8030412
Goll JB, Li S, Edwards JL, Bosinger SE, Jensen TL, Wang Y, Hooper WF, Gelber CE, Sanders KL, Anderson EJ, et al. Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine. Vaccines. 2020; 8(3):412. https://doi.org/10.3390/vaccines8030412
Chicago/Turabian StyleGoll, Johannes B., Shuzhao Li, James L. Edwards, Steven E. Bosinger, Travis L. Jensen, Yating Wang, William F. Hooper, Casey E. Gelber, Katherine L. Sanders, Evan J. Anderson, and et al. 2020. "Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine" Vaccines 8, no. 3: 412. https://doi.org/10.3390/vaccines8030412
APA StyleGoll, J. B., Li, S., Edwards, J. L., Bosinger, S. E., Jensen, T. L., Wang, Y., Hooper, W. F., Gelber, C. E., Sanders, K. L., Anderson, E. J., Rouphael, N., Natrajan, M. S., Johnson, R. A., Sanz, P., Hoft, D., & Mulligan, M. J. (2020). Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine. Vaccines, 8(3), 412. https://doi.org/10.3390/vaccines8030412