Location describes spatial and temporal environments. It distinguishes molecules and reactions found in different kinds of cells, tissues and organs. Without it we would get the model of a super-cell, which can do everything. Imagine the network for each cell being drawn on an overhead-transparency. Then the view without location information would be all these transparencies layered on top of each other.

Signaling needs the location context. Subcellular location plays an important role in the activity of many compounds. For example, transcription factors like NF-kappaB are only active in the nucleus and Ras is only active after recruitment to the inner plasma membrane. Since all signaling takes place in the complex matrix that is the multicellular organism, we first need a good model of the spatio-temporal segmentation of the organisms.

Each component in the network has two lists of location objects. One list contains all locations where experiments have confirmed the presence of the component, the other list contains all locations where experiments have confirmed its absence - which is necessary to distinguish between cases where the component is absent and cases where its status has not been investigated. For molecules, the locations describe where the molecules have been shown to be expressed, or have been shown not to be expressed. For reactions, the locations describe in what kind of system the reactions have been confirmed, or have been found not to happen.

Relevant aspects of location include:

• subcellular location. Examples: in the nucleus, plasma-membrane associated or spanning, mitochondrial, in the cytosol.
• tissue/cellular location. Examples: liver, kidney, body, glomeruli, Schwann cells, adipose tissue
• developmental stage. Example: Carnegie stages in human.
• species. Examples: vertebrata, mammalia, human, rat, mouse

The location items often relate to each other in tree-like schemes. A human, for example, is a vertebrate in the taxonomic dimension. Glomeruli are a substructure of the kidney. This classification is necessary to avoid state explosion --- otherwise we would have to insert a separate entry for each subtype, when the supertype is mentioned in the literature.

Sequences and molecular weights differ between orthologs. While the species is categorized as part of the location of a molecule, these orthologs are not different states of the same molecule, they are different members of a group of molecules. The molecules from different species are stored as members of their orthogroup entry.

The experimental proof for a reaction is usually obtained in artificial systems. We cannot claim that a reaction takes place in a cell in vivo simply because all involved molecules are found in this cell. We have to link the reaction to the location for which it was proven.

When we have further information that depends on the location, we store this information in the relation between Location and Molecule/Reaction.

Locations in TRANSPATH^® can contain up to five different parameter that are listed below. These attributes are used separately or in combination.