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Review
. 2013 Jul 1;30(13):1101-16.
doi: 10.1089/neu.2012.2631.

Systems Biology Approaches for Discovering Biomarkers for Traumatic Brain Injury

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Free PMC article
Review

Systems Biology Approaches for Discovering Biomarkers for Traumatic Brain Injury

Jacob D Feala et al. J Neurotrauma. .
Free PMC article

Abstract

The rate of traumatic brain injury (TBI) in service members with wartime injuries has risen rapidly in recent years, and complex, variable links have emerged between TBI and long-term neurological disorders. The multifactorial nature of TBI secondary cellular response has confounded attempts to find cellular biomarkers for its diagnosis and prognosis or for guiding therapy for brain injury. One possibility is to apply emerging systems biology strategies to holistically probe and analyze the complex interweaving molecular pathways and networks that mediate the secondary cellular response through computational models that integrate these diverse data sets. Here, we review available systems biology strategies, databases, and tools. In addition, we describe opportunities for applying this methodology to existing TBI data sets to identify new biomarker candidates and gain insights about the underlying molecular mechanisms of TBI response. As an exemplar, we apply network and pathway analysis to a manually compiled list of 32 protein biomarker candidates from the literature, recover known TBI-related mechanisms, and generate hypothetical new biomarker candidates.

Figures

FIG. 1.
FIG. 1.
Schematic representation of a systems biology approach to TBI. Pathways and protein interaction networks act as a scaffold to integrate heterogeneous information from high-throughput molecular data sets, distilling the complex molecular TBI response into testable hypotheses. PPI, protein-protein interaction; TBI, traumatic brain injury.
FIG. 2.
FIG. 2.
Projection onto the PPI network of all interconnected TBI biomarker candidates (pink) plus seven novel proteins found to interact with at least five biomarker candidates in the network (blue). The number of citations for each biomarker candidate is denoted by the size of the node. Proteins were categorized by biological function by manual inspection of KEGG, Reactome, and Gene Ontology annotations for each protein. Immune system proteins have many direct interactions with proteins associated with Alzheimer's disease and apoptosis, as well as indirect interactions with these proteins through well-studied biomarkers SPTAN1 and GFAP. PPI, protein-protein interaction; TBI, traumatic brain injury; KEGG, Kyoto Encyclopedia of Genes and Genomes; SPTAN1, spectrin, alpha, non-erythrocytic 1 (alpha-fodrin); GFAP, glial fibrillary acidic protein.

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