Pathway Search System developed in Cell Signaling Networks Database

Takako Igarashi, National Institute of Health Sciences
(Division of Chem-Bio Informatics, 1-18-1, Kamiyoga, Setagaya, Tokyo, Japan 158, 
taka@nihs.go.jp)

	I have been developing a Cell Signaling Networks Database (CSNDB) [1] 
which is a database for cellular signal transduction of human. Signal transduction is 
compiled as combination of binary relations which consist of two groups of 
biomolecules and pathways which consist of series of binary relations.  A binary 
relation corresponds to one step of signal transfer and a pathway corresponds to a 
biological response. CSNDB is constructed on Ace4.3 and contains 1039 binary 
relations and 1026 biomolecules at present.
	One of main problems of compiling cellular signal transduction is on defining 
pathways. A boundary of each pathway is hard to be defined, because a whole map of 
cellular signaling networks has not yet been elucidated and new experimental facts 
accumulated in a rapid pace often change topologies of steps of signal transfer. In 
addition, since pathways in cells crossly interact mutually so as to construct 
elaborate networks in the cell, boundaries of pathways can be regarded differently in 
respect of conceptions of individual researchers. 
	One practical solution of the problem is making a system which provides 
possible pathways deduced from aggregate of binary relations. This kind of deduction 
is a suitable task of logic programming languages. I developed a pathway search 
system [2] using a deductive engine "Coral" [3] which is a Prolog-type logic 
programming language. With this system user can retrieve  possible pathways including 
a fixed molecule which he selects. The system configuration is described in figure 1. 
	In the future, when entire mechanisms of cellular signal transduction will be 
elucidated, boundaries of pathways will be defined uniformly and this search system 
will not be required. However currently this search system is useful for referring signal 
transduction pathways, analyzing pathways, and predicting possible pathways which 
succeed a particular molecule. 
	Though the present search system is started by reading a list of binary 
relations in ASCII dumped from ACEDB, I strongly wish to make it called by ACEDB 
directory. Any advises will be greatly appreciated. 

[1] Igarashi,T. and Kaminuma,T. (1997) Development of Cell Signaling Networks 
Database, Pacific Symposium on Biocomputing '97, World Scientific, pp.187-197.
[2] http://geo.nihs.go.jp/csndb.html/path_query.html
[3] Bancilhon, F. and Ramakrishman, R. A. (1989) An amateur's introduction to 
recursive query processing strategies. In Mylopolos and Brodie (eds), Reading in 
Artificial Intelligence and Databases, Morgan Kaufmann, Los Altos, CA, pp.376-430. 

Fig 1. The system configuration of the pathway search system developed in CSNDB.