Int J Burn Trauma 2012;2(1):1-10
Review Article
Computational and systems biology in trauma and sepsis: current state and
future perspectives
Gary An, Gary Nieman, Yoram Vodovotz
Department of Surgery, University of Chicago, Chicago, IL 60637, USA; Department of Surgery, Upstate Medical University,
Syracuse, NY 13210, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; Center for Inflammation
and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Received December 30, 2011; accepted January 15, 2012; Epub February 1, 2012; Published February 28, 2012
Abstract: Trauma, often accompanied by hemorrhage, is a leading cause of death worldwide, often leading to
inflammation-related late complications that include sepsis and multiple organ failure. These secondary complications are a
manifestation of the complexity of biological responses elicited by trauma/hemorrhage, responses that span most, if not all,
cell types, tissues, and organ systems. This daunting complexity at the patient level is manifest by the near total dearth of
available therapeutics, and we suggest that this dire condition is due in large part to the lack of a rational, systems-oriented
framework for drug development, clinical trial design, in-hospital diagnostics, and post-hospital care. We have further
suggested that mechanistic computational modeling can form the basis of such a rational framework, given the maturity of
systems biology / computational biology. Herein, we briefly summarize the state of the art of these approaches, and highlight
the biological insights and novel hypotheses derived from these approaches. We propose a rational framework for
transitioning through the currently fragmented process from identification of biological networks that are potential therapeutic
targets, through clinical trial design, to personalized diagnosis and care. Insights derived from systems and computational
biology in trauma and sepsis include the centrality of Damage-Associated Molecular Pattern molecules as drivers of both
beneficial and detrimental inflammation, along with a novel view of multiple organ dysfunction as a cascade of containment
failures with distinct implications for therapy. Finally, we suggest how these insights might be best implemented to drive
transformational change in the fields of trauma and sepsis. (IJBT1112001).
Keywords: trauma, sespsis, systems biology, computational biology, mathematical modeling
Address correspondence to:
Dr. Yoram Vodovotz
Department of Surgery
University of Pittsburgh
W944 Starzl Biomedical Sciences Tower
200 Lothrop St.
Pittsburgh, PA 15213
Tel.: 412-647-5609
Fax: 412-383-5946
E-mail: vodovotzy@upmc.edu
Review Article
Computational and systems biology in trauma and sepsis: current state and
future perspectives
Gary An, Gary Nieman, Yoram Vodovotz
Department of Surgery, University of Chicago, Chicago, IL 60637, USA; Department of Surgery, Upstate Medical University,
Syracuse, NY 13210, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; Center for Inflammation
and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Received December 30, 2011; accepted January 15, 2012; Epub February 1, 2012; Published February 28, 2012
Abstract: Trauma, often accompanied by hemorrhage, is a leading cause of death worldwide, often leading to
inflammation-related late complications that include sepsis and multiple organ failure. These secondary complications are a
manifestation of the complexity of biological responses elicited by trauma/hemorrhage, responses that span most, if not all,
cell types, tissues, and organ systems. This daunting complexity at the patient level is manifest by the near total dearth of
available therapeutics, and we suggest that this dire condition is due in large part to the lack of a rational, systems-oriented
framework for drug development, clinical trial design, in-hospital diagnostics, and post-hospital care. We have further
suggested that mechanistic computational modeling can form the basis of such a rational framework, given the maturity of
systems biology / computational biology. Herein, we briefly summarize the state of the art of these approaches, and highlight
the biological insights and novel hypotheses derived from these approaches. We propose a rational framework for
transitioning through the currently fragmented process from identification of biological networks that are potential therapeutic
targets, through clinical trial design, to personalized diagnosis and care. Insights derived from systems and computational
biology in trauma and sepsis include the centrality of Damage-Associated Molecular Pattern molecules as drivers of both
beneficial and detrimental inflammation, along with a novel view of multiple organ dysfunction as a cascade of containment
failures with distinct implications for therapy. Finally, we suggest how these insights might be best implemented to drive
transformational change in the fields of trauma and sepsis. (IJBT1112001).
Keywords: trauma, sespsis, systems biology, computational biology, mathematical modeling
Address correspondence to:
Dr. Yoram Vodovotz
Department of Surgery
University of Pittsburgh
W944 Starzl Biomedical Sciences Tower
200 Lothrop St.
Pittsburgh, PA 15213
Tel.: 412-647-5609
Fax: 412-383-5946
E-mail: vodovotzy@upmc.edu
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