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SYSTEMS BIOLOGY

The term “Systems Biology” is being using with increasing incidence in the scientific literature. However, a review of the papers published with the keyword “systems biology” quickly demonstrates that this discipline is quite broad and that the exact definition of a “systems biology approach” is unclear. Systems biology can be defined as “the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life”. The key distinction in a systems biology approach to research is that instead of analyzing individual components or aspects of an organism, such as lipids or a specific gene/protein, the focus is placed on examining how all of the components interact as a single system. It is thought that by focusing on the entire organism as a single unit that biological mechanisms can be elucidated. The above figure taken from Ahn et al. (2006) demonstrates this point in that systems biology focuses on the relationships between components and not necessarily the components themselves. For example, the disease atherosclerosis exhibits a complex development that involves multiple components of the inflammatory cascade as well as the immune system. Accordingly, it is difficult to attribute any one specific marker (i.e., metabolite, gene or protein) with risk for disease. Instead, by examining the system as a whole and exploring multiple pathways simultaneously, a greater indication of organism state and current phenotype can be acquired. This knowledge can in turn be applied to develop therapeutic interventions and treatment strategies that address the overall imbalance (e.g. shift from equlibrium) in the system.

Systems Biology
Figure from Ahn et al (2006) The clinical applications of a systems approach. PLoS Medicine. 3(7):e209. doi:10.1371/journal.pmed.0030209

Systems biology emerged out of the Human Genome Project, which provided the initial impetus to think of science in terms of large-scale systemic datasets. The commensurate increase in our ability to acquire data via the technologies in the "omics-cascade" has greatly enhanced our ability to probe biological mechanisms. The science of systems biology has been greatly facilitated and convergently evolved with increased access to the internet, on-line databases, data storage facilities and computing power. Of particular interest is the development that systems biology is truly interdisciplinary in that no single discipline can lay claim to being “systems biology”. Instead, it is a conglomeration of biologists, chemists, statisticians, computer scientists, mathematicians, physicists, and engineers, among others. Systems biology studies are providing the research community with a growing understanding of how transcribed genes and their resulting translated proteins give rise to a suite of metabolites that determine biological form and function. In a sense, systems biology can be considered to be an investigation into the factors that determine the phenotype of the organism, which is often the endpoint of most interst, at least in a clinical setting.

The Omics Cascade
omics cascade

We are interested in developing bioinformatics tools to explore the relationships among the different members of the eicosanoid cascade. In collaboration with the Kyoto University Bioinformatics Center, we have been expanding their pathway description for lipid metabolism, with a focus on the arachidonic acid cascade. Recent developments in the KEGG hierarchy enable the mapping of both genomics and metabolomics data onto KEGG pathways using the KegArray application. These efforts are being combined in collaboration with Åsa Wheelock’s laboratory at the Karolinska University Hospital, which focuses on the proteomics of inflammatory processes. Taken together, these efforts are designed to further our long-term goal of developing systems biology approaches to describing the inflammatory process.
KEGG
One of the underlying aims of this work is to develop systems biology approaches to broaden our understanding of cardiovasecular disease towards the goal of developing a cure. We are interested in generating biological networks of atherosclerosis using metabolomics and transcriptomic data to probe and understand the function of eicosanoids in inflammatory-related pathologies. These procedures will be useful to understand the fundamental processes behind the inflammatory component of cardiovascular disease, provide information on cross-talk between the different pathways, and potentially identify novel treatments. The methods developed in this work are designed to be applicable to both vascular and pulmonary disorders. The application of a systems biology approach will assist in the shift from treating a disease target to treating pathways to treating an individual person – a true shift to personalized medicine. Similar to critical care physicians, systems biology infers macroscopic behavior and function as well as methods for modification or prediction from integrated data analysis. Accordingly, by combining systems phenotyping with in-depth investigations of biomolecular mechanisms, we will enable a paradigm shift in our understanding of disease pathology and will advance translational medicine, combination therapies, integrative medicine, and personalized medicine, moving from disease management to health promotion.

 

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