Systems biology and the discovery of diagnostic biomarkers

Abstract. Systems biology is an approach to the science that views biology as an information science, studies biological systems as a whole and their interactions with the environment. This approach, for the reasons described here, has particular power in the search for informative diagnostic biomarkers of diseases because it focuses on the fundamental causes and keys on the identification and understanding of disease-perturbed molecular networks. In this review, we describe some recent developments that have used systems biology to address complex diseases -prion disease and drug induced liver injury-and use these as examples to illustrate the importance of understanding network structure and dynamics. The knowledge of network dynamics through in vitro experimental perturbation and modeling allows us to determine the state of the networks, to identify molecular correlates, and to derive new disease treatment approaches to reverse the pathology or prevent its progress into a more severe state through the manipulation of network states. This general approach, including diagnostics and therapeutics, is becoming known as systems medicine. Keywords: Systems biology, biomarkers, systems medicine, prion disease, drug induced liver injury, microRNA, organ-specific proteins Systems biology and systems medicine An approach to analyzing biological systems, which we call systems biology, has emerged over the past 10 years or so -an approach that looks at biology as an information science, studies systems as a whole and their interactions with the environment. This approach recognizes that biological information in living systems is captured, transmitted, modulated, and integrated by biological networks made up of molecular components as well as cells. This approach differs from early "systems approaches to biology" in that it attempts both a bottom-up approach (using large molecular datasets) and a top-down approach (using computational modeling and simulations) where there is an attempt to trace observations of complex phenotypes back to information encoded in the genome. * Corresponding author. Tel.: +1 206 732 1336; Fax: +1 206 732 1253; E-mail: kwang@systemsbiology.org. Two fundamental types of biological information, the digital information of the genome and interacting information from the environment, are both contributors to the fundamental mechanisms of life -evolution, development, physiological responses, aging and the onset and progression of diseas