Systems biology approaches have become indispensable in processing huge and heterogeneous biomedical data, extracting essential information and forming novel hypotheses from various experimental results. In the field of neurotrauma studies, decades of efforts in animal experiments and clinical studies accumulated wealthy knowledge on the pathophysiology of traumatic brain injury (TBI). Application of systems biology strategies to holistically analyze the complex molecular pathways and networks of brain trauma can be of high importance due to its impact on biomarker research. In this chapter, we discuss current available systems biology strategies, databases, and tools and their applications to existing TBI data sets that can be used to identify new biomarker candidates investigating the different underlying molecular mechanisms and pathways of TBI responses.
The emerging large-scale and high-throughput technologies in molecular biology allowed rapid accumulation of vast biomedical data and its documentation in open access databases. This entailed unraveling sequences of whole genomes for thousands of species, identification of new genes and proteins, and studying biological function of these interacting biomolecules. This has provided scientists with the tools and material to investigate complex molecular mechanisms of biological systems (Kitano, 2002; Wang et al., 2010). However, researchers could be easily overwhelmed by this enormous amount of data and by the intricacy of the large number of biomolecules that are intertwined in a system. In fact, the complexity of biological processes is challenging the traditional reductionist thinking of biomedical studies investigating a few biomolecules for their effects under well-controlled experimental conditions (Strange, 2005). Although small-scale experiments are essential in accumulating knowledge and validating hypotheses, they are not effective in incubating novel ideas and hypotheses of the molecular mechanisms of complicated biological phenomenon. This instigated the birth of the new field of systems biology.
Systems biology emerged from molecular biology as an interdisciplinary subject that employs mathematics and computer science to study complex molecular mechanisms of biological phenomenon in a systematic and holistic way. In contrast to reductionist thinking that decomposes a biological system into small components and studies them separately, systems biology explores the molecular basis of the whole biological system by studying its construction, operation, different components’ coordination, and system responses to external perturbations (Strange, 2005). By focusing on the interactions of multiple different biomolecules, systems biology approaches have been developed to incorporate heterogeneous biomedical data and knowledge to explain experimental results, provide insights into the molecular basis of complex diseases, prioritize genes and proteins from large-scale screenings, and discover molecular biomarkers and potential drug targets (Kaimal et al., 2011; Noorbakhsh et al., 2009; Ptitsyn et al., 2008).
Today, systems biology approaches have become indispensable in processing huge and heterogeneous biomedical data, extracting essential information and forming novel hypotheses from various experimental results. In the field of neurotrauma studies, decades of efforts in animal experiments and clinical studies accumulated wealthy knowledge on the pathophysiology of TBI. Meanwhile, we recognize that the complexity of the molecular mechanisms underpinning the primary and the secondary injury induced by traumatic insult are still poorly understood (Albert-Weissenberger and Sirén, 2010). This significantly hindered the discovery of molecular biomarkers for diagnosis and prognosis of TBI and the development of neurotrauma therapeutics. As more neurotrauma data are garnered and become available to the whole community, systems biology is in immense need for researchers in the field to incorporate these experimental data and knowledge so as to decipher molecular mechanisms and discover novel molecular biomarkers. Actually, systems biology has been applied in some neurotrauma studies and a couple of review articles have been published recently (Feala et al., 2013; Zhang et al., 2010). However, the full potential of systems biology is not yet recognized by the whole neurotrauma community.
In this chapter, we will introduce systems biology basics and methodologies. We will focus on three groups of approaches: (1) gene set analysis; (2) pathway analysis; and (3) protein-protein interaction (PPI) analysis. All these methods can be applied in neurotrauma studies, where they help gain insights into molecular mechanisms or infer novel biomarkers. The actual application of systems biology in neurotrauma studies will be briefly reviewed in the second part of this chapter. This chapter provides general guidance and inspires more neurotrauma studies that exploit the predictive power of systems biology.
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