Bio-Curation for Cellular Signalling: The KAMI Project.

The general question of what constitutes bio-curation for rule-based modelling of cellular signalling is posed. A general approach to the problem is presented, based on rewriting in hierarchies of graphs, together with a specific instantiation of the methodology that addresses our particular bio-curation problem. The current state of the ongoing development of the KAMI bio-curation tool, based on this approach, is outlined along with our plans for future development.

Intrinsic information carriers in combinatorial dynamical systems.

Many proteins are composed of structural and chemical features--"sites" for short--characterized by definite interaction capabilities, such as noncovalent binding or covalent modification of other proteins. This modularity allows for varying degrees of independence, as the behavior of a site might be controlled by the state of some but not all sites of the ambient protein. Independence quickly generates a startling combinatorial complexity that shapes most biological networks, such as mammalian signaling systems, and effectively prevents their study in terms of kinetic equations-unless the complexity is radically trimmed.

Internal coarse-graining of molecular systems.

Modelers of molecular signaling networks must cope with the combinatorial explosion of protein states generated by posttranslational modifications and complex formation. Rule-based models provide a powerful alternative to approaches that require explicit enumeration of all possible molecular species of a system. Such models consist of formal rules stipulating the (partial) contexts wherein specific protein-protein interactions occur.