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Title: Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

Abstract

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenicmore » *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines.« less

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1030442
Report Number(s):
PNNL-SA-84155
Journal ID: ISSN 0264-410X; VACCDE; KP1601010; TRN: US201124%%203
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Vaccine
Additional Journal Information:
Journal Volume: 29; Journal Issue: 41; Journal ID: ISSN 0264-410X
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ANIMALS; BIOLOGICAL MODELS; BIOLOGICAL PATHWAYS; BIOLOGY; BIOTECHNOLOGY; BRUCELLA; CATTLE; DESIGN; DISEASES; DRUGS; FUNCTIONALS; GENES; IMMUNOLOGY; INFECTIOUS DISEASES; MUTANTS; MYCOBACTERIUM; PATHOGENESIS; PATHOGENS; SALMONELLA; VACCINES; Systems biology; Computational biology; Transcriptome; Zoonoses; Brucellosis; Salmonellosis; Johne's disease; Interactome; Vaccine

Citation Formats

Adams, Leslie G., Khare, Sangeeta, Lawhon, Sara D., Rossetti, Carlos A., Lewin, Harris A., Lipton, Mary S., Turse, Joshua E., Wylie, Dennis C., Bai, Yu, and Drake, Kenneth L. Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development. United States: N. p., 2011. Web. doi:10.1016/j.vaccine.2011.05.080.
Adams, Leslie G., Khare, Sangeeta, Lawhon, Sara D., Rossetti, Carlos A., Lewin, Harris A., Lipton, Mary S., Turse, Joshua E., Wylie, Dennis C., Bai, Yu, & Drake, Kenneth L. Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development. United States. doi:10.1016/j.vaccine.2011.05.080.
Adams, Leslie G., Khare, Sangeeta, Lawhon, Sara D., Rossetti, Carlos A., Lewin, Harris A., Lipton, Mary S., Turse, Joshua E., Wylie, Dennis C., Bai, Yu, and Drake, Kenneth L. Thu . "Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development". United States. doi:10.1016/j.vaccine.2011.05.080.
@article{osti_1030442,
title = {Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development},
author = {Adams, Leslie G. and Khare, Sangeeta and Lawhon, Sara D. and Rossetti, Carlos A. and Lewin, Harris A. and Lipton, Mary S. and Turse, Joshua E. and Wylie, Dennis C. and Bai, Yu and Drake, Kenneth L.},
abstractNote = {The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines.},
doi = {10.1016/j.vaccine.2011.05.080},
journal = {Vaccine},
issn = {0264-410X},
number = 41,
volume = 29,
place = {United States},
year = {2011},
month = {9}
}