Systems biology, a new scientific discipline, aims to study the behavior of a biological organization or process in order to understand the function of a dynamic system. This commentary will put into perspective topics discussed in this issue of Alcohol Research & Health, provide insight into why alcohol-induced disorders exemplify the kinds of conditions for which a systems biological approach would be fruitful, and discuss the opportunities and challenges facing alcohol researchers. KEY WORDS: Alcohol-induced disorders; alcohol research; biomedical research; systems biology; biological systems; mathematical modeling; genomics; epigenomics; transcriptomics; metabolomics; proteomics
Until recently, most biologists' efforts have been devoted to reducing complex biological systems to the properties of individual molecules. However, with the completed sequencing of the genomes of humans, mice, rats, and many other organisms, technological advances in the fields of high-throughput genomics1 and functional genomics2 have generated enormous amounts of information on the properties of genes, RNAs,3 proteins, and metabolic products (i.e., metabolites) in an organism. The billions of data points generated by these high-throughput studies are far beyond the reach of reductionist approaches. High-throughput technologies have offered biologists tremendous opportunities but also have created considerable challenges. How can we take advantage of this wealth of information to understand its biological significance in health and disease? Systems biology is an emerging discipline that deals with, and takes advantage of, these enormous amounts of data. Although scientists and engineers have applied the concept of an integrated systemic approach for years, systems biology has only emerged as a new, distinct discipline to study complex biological systems in the past several years. A database search using the phrase "systems biology" in the ISI Web of Science has found only 3 publications in 2001; in 2006, this number had reached 575 (see figure 1).
With the emergence of this powerful new discipline, we are tempted to ask the following questions: Is systems biology suitable for alcohol research? What kinds of alcohol-related problems can we address using a systems biology approach? What opportunities and challenges are there in current and future research? These are the kinds of questions that the articles in this special systems biology issue of Alcohol Research & Health intend to address. In this commentary, we will try to put the topics discussed in this issue into perspective, provide views on the significance of systems biology for alcohol research, and discuss opportunities and challenges facing alcohol researchers.
WHAT IS SYSTEMS BIOLOGY?
Systems biology is a new scientific discipline that studies the behaviors of complex biological organizations or processes through the integration of diverse quantitative information and mathematical modeling to generate a predictive hypothesis on the functions of the dynamic biological system (Aderem 2005; Auffray et al. 2003; Hood et al. 2004; Kirschner 2005; Liu 2005; O'Malley and Dupre 2005; Weston and Hood 2004).
Systems biology may have quite different meanings to different people. In general, systems biologists can be organized into two camps. In the first camp, the "systems-theoretic biologists" think that the focus of systems biology is to elucidate system principles and properties of operation based on component interactions in the biological system (Bork and Serrano 2005; O'Malley and Dupre 2005). To them, systems biology is very abstract and precise. The mere integration of constituents in the system for understanding the emergent properties4 of component interactions is insufficient for these theory-oriented systems biologists. However, the majority of today's systems biologists, who can be described as "pragmatic systems biologists," are gathered in the other camp (O'Malley and Dupre 2005). …