Review ARTICLE

Front. Neurol., 27 June 2014 | http://dx.doi.org/10.3389/fneur.2014.00102

How implementation of systems biology into clinical trials accelerates understanding of diseases

imageBibiana Bielekova1,2*, imageYoram Vodovotz3,4, imageGary An4,5 and imageJohn Hallenbeck6
  • 1Neuroimmunological Diseases Unit, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD, USA
  • 2Center for Human Immunology of the National Institutes of Health, Bethesda, MD, USA
  • 3Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
  • 4Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine, Pittsburgh, PA, USA
  • 5Department of Surgery, Northwestern University, Chicago, IL, USA
  • 6Stroke Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD, USA

Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the genetic and environmental diversity of human subjects, identification of critical elements related to a particular disease process from cross-sectional studies requires prohibitively large cohorts. Alternatively, implementation of systems biology principles to interventional clinical trials represents a unique opportunity to gain predictive understanding of complex diseases in comparatively small cohorts of patients. This paper reviews systems biology principles applicable to translational research, focusing on lessons from systems approaches to inflammation applied to multiple sclerosis. We suggest that employing systems biology methods in the design and execution of biomarker-supported, proof-of-principle clinical trials provides a singular opportunity to merge therapeutic development with a basic understanding of disease processes. The ultimate goal is to develop predictive computational models of the disease, which will revolutionize diagnostic process and provide mechanistic understanding necessary for personalized therapeutic approaches. Added, biologically meaningful information can be derived from diagnostic tests, if they are interpreted in functional relationships, rather than as independent measurements. Such systems biology based diagnostics will transform disease taxonomies from phenotypical to molecular and will allow physicians to select optimal therapeutic regimens for individual patients.

Keywords: systems biology, clinical trials, clinical trials methodology, multiple sclerosis, polygenic diseases

Citation: Bielekova B, Vodovotz Y, An G and Hallenbeck J (2014) How implementation of systems biology into clinical trials accelerates understanding of diseases. Front. Neurol. 5:102. doi: 10.3389/fneur.2014.00102

Received: 28 March 2014; Accepted: 05 June 2014;
Published online: 27 June 2014.

Edited by:

Amy Lovett-Racke, The Ohio State University, USA

Reviewed by:

Nancy Monson, University of Texas Southwestern Medical Center, USA
Marie Csete, Huntington Medical Research Institutes, USA

Copyright: © 2014 Bielekova, Vodovotz, An and Hallenbeck. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Bibiana Bielekova, NIH/NINDS/NIB, Bld10/R, 5C103, 10 Center Drive, MSC1400, Bethesda, MD 20892, USA e-mail: bibi.bielekova@nih.gov