Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort.
Casey P Shannon, Travis M Blimkie, Rym Ben-Othman, Nicole Gladish, Nelly Amenyogbe, Sibyl Drissler, Rachel D Edgar, Queenie Chan, Mel Krajden, Leonard J Foster, Michael S Kobor, William W Mohn, Ryan R Brinkman, Kim-Anh Le Cao, Richard H Scheuermann, Scott J Tebbutt, Robert E W Hancock, Wayne C Koff, Tobias R Kollmann, Manish Sadarangani, Amy Huei-Yi Lee
Author Information
Casey P Shannon: Prevention of Organ Failure (PROOF) Centre of Excellence and Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada.
Travis M Blimkie: Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Rym Ben-Othman: Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Nicole Gladish: Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada.
Nelly Amenyogbe: Telethon Kids Institute, Perth Children's Hospital, University of Western Australia, Nedlands, WA, Australia.
Sibyl Drissler: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
Rachel D Edgar: Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada.
Queenie Chan: Department of Biochemistry & Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Mel Krajden: British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Leonard J Foster: Department of Biochemistry & Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Michael S Kobor: Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada.
William W Mohn: Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Ryan R Brinkman: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
Kim-Anh Le Cao: Melbourne Integrative Genomics, School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia.
Richard H Scheuermann: Department of Informatics, J. Craig Venter Institute, La Jolla, CA, United States.
Scott J Tebbutt: Prevention of Organ Failure (PROOF) Centre of Excellence and Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada.
Robert E W Hancock: Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Wayne C Koff: Human Vaccines Project, New York, NY, United States.
Tobias R Kollmann: Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Manish Sadarangani: Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Amy Huei-Yi Lee: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
Background: Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. Methods: We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres. Results: Using both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response. Conclusion: This study provides further evidence that baseline cellular and molecular characteristics of an individual's immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.
