Is Systems Biology the Key to Preventing the Next Pandemic?

Tisoncik, Jennifer R.; Belisle, Sarah E.; Diamond, Deborah L.; Korth, Marcus J.; Katze, Michael G.

doi:10.2217/fvl.09.53

Cited by 7 publications

(5 citation statements)

References 47 publications

(44 reference statements)

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“…Similar approaches with other host expression pathways and the addition of other virulent and avirulent pathogens across several viral families might provide a mosaic of signatures to quickly and rapidly assess the danger posed by a particular emergent pathogen. Together, the data illustrate that the infrastructure of systems biology provides a unique and novel platform to evaluate emergent viruses and demonstrates the rapid analysis not typically associated with systems‐based analysis .…”

Section: Expanding Systems‐based Studies To Translational Applicationsmentioning

confidence: 92%

Bugs in the system

Menachery

Baric

2013

Immunological Reviews

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Summary Immunity to respiratory virus infection is governed by complex biological networks that influence disease progression and pathogenesis. Systems biology provides an opportunity to explore and understand these multifaceted interactions based on integration and modeling of multiple biological parameters. In this review, we describe new and refined systems-based approaches used to model, identify, and validate novel targets within complex networks following influenza and coronavirus infection. In addition, we propose avenues for extension and expansion that can revolutionize our understanding of infectious disease processes. Together, we hope to provide a window into the unique and expansive opportunity presented by systems biology to understand complex disease processes within the context of infectious diseases.

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Section: Expanding Systems‐based Studies To Translational Applicationsmentioning

confidence: 92%

Bugs in the system

Menachery

Baric

2013

Immunological Reviews

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“…As a first measure, however, one would want to investigate some of the stronger hypotheses generated by the model experimentally [36•, 37, 38]. A much higher time-resolved investigation of the innate IA in progressors and non-progressors before peak-viremia using functional genomics and proteomics tools would allow to directly establish IA kinetics and compare them.…”

Section: Propositionsmentioning

confidence: 99%

Dynamics of innate immunity are key to chronic immune activation in AIDS

Benecke

Gale²,

Katze

2012

Current Opinion in HIV and AIDS

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Purpose of review We propose here that the dynamics rather than the structure of cellular and viral networks plays a determining role in chronic immune activation of HIV infected individuals. A number of novel avenues of experimental analysis and modeling strategies is discussed to conclusively address these network dynamics in the future. Recent findings Recent insights into the molecular dynamics of immune activation and its control following SIV infection in natural host primates has provided possible alternate interpretations of SIV and HIV pathogenesis. Concomitant with insights gained in other host-pathogen systems, as well as an increased understanding of innate immune activation mechanisms, these observations lead to a new model for the timing of innate HIV immune-responses and a possible primordial role of this timing in programming chronic immune activation. Summary Chronic immune activation is today considered the leading cause of AIDS in HIV-infected individuals. Systems biology has recently lent arguments for considering chronic immune activation a result of untimely innate immune responses by the host to the infection. Future strategies for the analysis, comprehension, and incorporation of the dynamic component of immune activation into HIV vaccination strategies are discussed.

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“…In what will follow, we will discuss some recent insights into functional genome representations to add a novel layer of investigation to the problem of gene expression regulation, chromatin structural dynamics, and genome structurefunction relationships. These representations are thought to be particularly useful to compare genomes from closely related species and more importantly to provide new ideas of how to treat the case of two or more genomes operating together in a single cell such as is the case in infectious settings (Aderem et al 2011;Tisoncik et al 2009). To this end, we will first discuss two recent examples of successful network structure inference and dynamics analysis in systems virology, analyze the implications these results have for our thinking of genome function, and finally provide some ideas how to further investigate these systems using functional genome representations as a first step for a multiscale modeling effort.…”

Section: A Systems Biology Challenge: Multiscale Integrationmentioning

confidence: 99%

Critical Dynamics in Host–Pathogen Systems

Benecke

2012

Current Topics in Microbiology and Immunology

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Host-pathogen interactions provide a fascinating example of two or more active genomes directly exerting mutual influence upon each other. These encounters can lead to multiple outcomes from symbiotic homeostasis to mutual annihilation, undergo multiple cycles of latency and lysogeny, and lead to coevolution of the interacting genomes. Such systems pose numerous challenges but also some advantages to modeling, especially in terms of functional, mathematical genome representations. The main challenges for the modeling process start with the conceptual definition of a genome for instance in the case of host-integrated viral genomes. Furthermore, hardly understood influences of the activity of either genome on the other(s) via direct and indirect mechanisms amplify the needs for a coherent description of genome activity. Finally, genetic and local environmental heterogeneities in both the host's cellular and the pathogen populations need to be considered in multiscale modeling efforts. We will review here two prominent examples of host-pathogen interactions at the genome level, discuss the current modeling efforts and their shortcomings, and explore novel ideas of representing active genomes which promise being particularly adapted to dealing with the modeling challenges posed by host-pathogen interactions.

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Is Systems Biology the Key to Preventing the Next Pandemic?

Cited by 7 publications

References 47 publications

Bugs in the system

Bugs in the system

Dynamics of innate immunity are key to chronic immune activation in AIDS

Critical Dynamics in Host–Pathogen Systems

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