Network-based models in molecular biology

Abstract

Biological systems are characterized by a large number of diverse interactions. Interaction maps have been used to abstract those interactions at all biological scales ranging from food webs at the ecosystem level down to protein interaction networks at the molecular scale. Organisms consist of thousands of cells with hundreds of different types. Cells in turn contain millions of molecules comprising thousands of different chemical species. Our genome contains about 23,000 protein coding genes [89], and the estimated number of chemically different proteins (considering splice variants and posttranslational modifications) is at least an order of magnitude larger. It is difficult to estimate the true number of different proteins, because there are no reliable methods yet for predicting splice variants. For example, the NCBI database (www.ncbi.nlm.nih.gov) currently lists about 440,000 protein entries—many of them may however be redundant. In addition, our cells contain many other molecules with catalytic or regulatory functions, such as ribosomal RNA, tRNA, and small interfering RNA (siRNA). Further, the cells contain thousands of different lipid species and other small molecules serving as structural components of the cell or as substrates for the biochemical reactions executed by the metabolic program. Hence, our body is coordinating the activity and reactions of hundreds of thousands if not millions of different chemical species [60]. Even a single cell is a prototypic example of a complex system [84]. Although biological systems follow all basic physical and chemical principles, they cannot be modeled sufficiently using standard methods from those two disciplines. Typical physical models describe a system as either a small number of different entities (e.g. mechanics) or a large number of very similar or even identical elements (e.g. thermodynamics). Likewise, also chemical reaction systems can only be appropriately described if the number of reacting species is small. However, the behavior and fate of organisms cannot be described appropriately without considering the fact that they consist of a large number of very different interacting elements.