Systems Biolog: a working definition

Past investments in technology development have made it possible to systematically identify and characterize molecules and molecular interactions that define cellular pathways, tissues, organs and organisms. The combination of such systems-level experimentation and the use of quantitative and computational tools to integrate, visualize and analyse the resulting experimental data is termed Integrative or Systems Biology. The goal of this scientific approach is to obtain a quantitative and predictive understanding and solutions of fundamental biological problems based on dynamic relationships between genetic, molecular, cellular, physiological and environmental factors.

The need for integrative and systems-oriented approaches in science becomes clear when considering the Human Genome Project. The completion of this project was expected to rapidly accelerate the understanding of illnesses by identifying disease-causing gene variants. The problem is that simple gene variation cannot explain the basis of the most common serious illnesses, such as cancer, heart disease, diabetes, asthma, and neurodegenerative disease, which arise from accumulative effects on cellular and organismal physiology of multiple gene variations and environmental factors. Consequently, the systematic sequencing of the genome, or any other characterization at a singular biological level, is unlikely to uncover causes and cures of many complex diseases. To achieve these goals it will be necessary to obtain, integrate and analyze biological data spanning multiple biological levels. Combining these three steps into one scientific strategy is the essence of Systems Biology research.

A key component in Systems Biology is the use of modelling and computational tools for data analysis, system simulation and hypothesis generation . This use of quantitative methods has been successful employed in many biological and biomedical research areas, including epidemiology, pharmacology, physiology, neuroscience and ecology. An initial emphasis of Systems Biology is to implement analogous approaches in molecular and cellular biology where the capacity for generating genomics and proteomics data is well developed and the potential for short-term success is greatest. However, the progression of the field will ultimately enable more accurate simulations and descriptions of more complex biological systems, including human physiology and disease. With appropriate levels of abstraction, these models will span all levels of biological organisation, from genes and molecular pathways, to cells, organs, organisms and ecosystems.