Unravelling Nature's Networks: From Microarray and Proteomic Analysis to Systems Biology: University of Sheffield, 21–22 July 2003

Dramatic progress has been made recently in determining the genetic and molecular composition of cells. This has prompted the development of new approaches to the challenge of understanding how basic cellular mechanisms are coordinated to produce the dazzling complexity of living systems. To face this challenge fully, it is critical not only to know what genes and proteins are expressed in cells, but also to understand the spatiotemporal dynamics of their networks of interactions. The sheer scale and complexity of cellular interaction networks necessitates a multi-disciplinary effort in which sophisticated experimental techniques are employed in combination with computational analysis and mathematical modelling. Such approaches are beginning to provide insight into basic structures and mechanisms, and promise to become critical to the post-genomic mission of understanding the cell as a complex dynamical system. Determining network structure The basic topology of an interaction network is determined by the nodes (e.g. the genes or proteins) and by the edges between these nodes (interactions between genes and/or proteins). In addition to this, it is often appropriate to label the edges to show directionality of interactions (e.g. a transcription factor binding to a promoter) and the nature of an interaction (e.g. activating or inhibitory). The nodes and edges constitute the network (or graph). The network of all interacting species within a cell is enormous, and a full determination of its structure remains beyond the reach of current experimental techniques due to technical and practical constraints. However, in practice it is often more appropriate to focus on smaller sub-networks that play a direct role in a particular setting or process {such as the network of interactions involving the transcription factor nuclear factorκB (NF-κB) in inflammation [1]}. The structure of such sub-networks has traditionally been elucidated by intensive genetic and biochemical analysis. This results in reasonably detailed pictures of small fragments of the entire cellular