The Construction of the Knowledge Base of Immune
SystemYoshinobu Igarashi

Minoru Kanehisa

igarashi@kuicr.kyoto-u.ac.jp

kanehisa@kuicr.kyoto-u.ac.jp

Institute for Chemical Research, Kyoto University
Gokasho, Uji, Kyoto 611-0011, Japan

1 Introduction
The paradigm shift from experimentals to bioinformatics is apparent in many areas of biology. Thereare immediate demands to construct databases that are designed for computer analysis of biologicalphenomena. Speci cally, the immune system has been researched very intensely in experimentals
because it is essential to protect our bodies against viruses, bacteria, and other foreign things. The
immune system is made up of cell-cell interactions and cytoplasmic signal transductions. In recentyears many molecules have been identi ed and characterized, as well as many interactions among
them. Thus, we focus on the immune system and investigate most speci ed and embodied cell-cellinteractions. Among multicellular organisms, only vertebrates can have immune system in their bodies,and various events would occur by complicated interactions between speci ed cells, T-cells, B-cells,
macrophages, etc. In addition, cell di erentiation is deeply crosslinked to the immune system in termsof cells' roles, because cells are changing their characters through di erentiation by ligand stimulation.
Therefore when we try to understand the immune system, we must refer to cell di erentiation interms of signal transductions and analyze the pathways that result from many interactions. However,there is virtually no database for the immune system that refers to signal transductions and cell-cellinteractions. Our database is designed in a similar way as BRITE [1] database which contains cellcycles and early developing stages, and we can analyze systematically the immune system, for example,
by using the information of the whole genomes sequences.

2 Method
2.1

Knowledge base

We collected interaction data from experimental papers, and constructed a knowledge base of theimmune system. The knowledge base is made as a at le and is based on BRITE [1] format.
It includes cell-cell interactions concerning CD molecules and signal transductions mainly involving
cytokines. Our knowledge base is not yet made available as a WWW service, but we will incorporate
these data into BRITE and open it to public.
2.2

Genome data

The analysis is made for the whole genome sequences of 17 species:302

M. jannaschii
P. horikoshii
Bacteria
E. coli
B. subtilis
M. tuberculosis
C. trachomatis
Eukaryotes S. cerevisiae
ArchaeaM.thermoautotrophicum A. fulgidus
H. in uenzae
M. genitalium
A. aeolicus
B. burgdorferi

H. pylori
M. pneumoniae
Synechocystis
T. pallidum

In addition, 11 species with partial genomes are analyzed. All genome sequences are taken fromGENES database in KEGG [2].
2.3

Sequence similarity searchFirstly, we detected homologues of the molecules in our database. The similarity search was performedby ssearch [3] with cuto value of 250. Secondly, we evaluated the alignment and additional information
with manual checking. This includes the position in the genome and we also checked the neighbors.

3 Results and Discussions
We have found three sequences which have high similarity with human integrin alpha chains in Synechocystis, though Synechocystis is not a multicellular organism. We also found WD repeat sequences,which are known to be found in only eukaryotes, in the neighbour upstream of the integrin alpha-likesequences in Synechocystis [4]. Therefore we guess that there is a possibility that these sequences are
not original in Synechocystis but transferred from eukaryotic organisms. Furthermore, Synechocystis
has homologs of cadherins that are engaged in cell-cell adhesion in multicellular organisms. We will
analyze and detect molecules that are interacting with these homologs.

Acknowledgements
This work was supported in part by a Grant-in-Aid for Scienti c Research on Priority Areas, `Genomescience', from the Ministry of Education, Science, Sports and Culture of Japan. The computation time
was provided by the Supercomputer Laboratory, Institute for Chemical Research, Kyoto University.

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