Constructing and Annotating GENES Databasein KEGG
Susumu Goto 1
goto@kuicr.kyoto-u.ac.jp
Hiroko Ishida 1
hiroko@scl.kyoto-u.ac.jp
Hiroyuki Ogata 1

ogata@kuicr.kyoto-u.ac.jp
12

Kotaro Shiraishi 2
kshirais@fqs.fujitsu.co.jp
Sanae Asanuma 1
sanae@scl.kyoto-u.ac.jp
Wataru Fujibuchi 1

wataru@kuicr.kyoto-u.ac.jp

Kayo Okamoto 1
kayo@scl.kyoto-u.ac.jp
Hidemasa Bono 1
bono@kuicr.kyoto-u.ac.jp
Minoru Kanehisa 1

kanehisa@kuicr.kyoto-u.ac.jp

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

KyushuSystemEngineering

Limited,

2-2-1

Momochihama,

Sawara-ku,

Fukuoka, 814-8589, Japan

1 Introduction
The KEGG (Kyoto Encyclopedia of Genes and Genomes) project is accumulating and computerizing
vast knowledge of biochemistry and molecular biology. In addition to the PATHWAY database,the GENES database is a basic element of the KEGG system. It describes gene IDs, gene names,
product names, chromosomal positions, gene classi cations, EC numbers, codon frequencies, aminoacid sequences and nucleotide sequences of over 20 species mainly with complete genomes.
Since the GENES database provides links between genomes and pathways, it can be an important
tool for functional genomics, where information of both genomes and pathways should be utilized. It
can also be used for comparative genomics, where whole genomes from several species are analyzed ata time. A major problem in such analyses is that there is no standard nomenclature for representing
genes and gene products. The names of the genes and gene products are often di erent between species
even if the products have the same function. The discrepancies are conspicuous when the genomes
are sequenced by di erent organizations. The construction of the GENES database is an e ort to ll
the gap and to provide a standardized resource for functional and comparative genomics.
Last year, we reported main concepts of the GENES database [4]. This paper focuses on how theGENES database is constructed and how gene annotations are made to maintain consistent information
among species.

2 Constructing GENES Database
The complete genome sequences are deposited in the GenBank database and distributed in a at leformat. We developed a parser program to extract information of genes from the GenBank at les.
It extracts gene IDs, chromosomal positions, names, products, EC numbers, amino acid sequences andnucleotide sequences. Because the format of the eld representation often di ers from species to species(i.e., from authors to authors) or even within species (i.e., containing variations and exceptions), theparser allows the user to specify, without changing the program, where and how the information should
be extracted. It also computes codon frequencies of each gene and the whole genome.
At this stage, the annotation is not good enough. Many genes remain hypothetical even if they
have similarity to known genes, and the majority of enzymes are not assigned EC numbers. This ispartly because di erent authors adopt di erent criteria for interpretation of signi cant homologies andbecause some organizations do not invest much on informatics e orts of functional annotation. We226

GenBank
flat file

Parser

Linking to SWISS-PROTand original databases

Partiallyannotated
GENES

Annotated
GENES

GFIT
Manual check of EC
number and annotation

User specification

Figure 1: Construction ow of the GENES database.
nd numerous cases where GenBank annotations are insucient. In order to facilitate our annotation
process, the GENES database is then integrated as part of the DBGET/LinkDB system [2] and it isalso linked to the genome map browser of the KEGG system [3].

3 Annotating Genes in the GENES Database
The EC number assignment of GENES is performed through amino acid sequence similarity searchagainst the whole genome sequences and SWISS-PROT by GFIT program [1]. GFIT reports possiblefunctions by trying to determine orthologous genes and automatically assigns EC numbers from theorthologous genes with known functions. Another program is used to make links from each entryof GENES to SWISS-PROT and original genome databases, such as TIGR microbial database, bychecking species and gene names described in both databases. The outputs of the latter program
are checked manually and annotations are re ned. Then the links to the PATHWAY database [3]and other databases are created automatically. The ow of the GENES database construction issummarized in Fig. 1. Currently we are developing tools for storing and manipulating the informationof GENES in a relational database, and for providing interactive annotation of genes via a WWWinterface.

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.

References[1] Bono, H., Ogata, H., Goto, S. and Kanehisa, M., Prediction of enzyme genes in complete genomes
by reconstruction of metabolic pathways, Genome Res., 8:203{210, 1998.
[2] Fujibuchi, W., Goto, S., Migimatsu, H., Uchiyama, I., Ogiwara, A., Akiyama, Y. and Kanehisa,M.,
DBGET/LinkDB: an Integrated Database Retrieval System, Pac. Symp. Biocomput. '98, 683{
694, 1998.
[3] Kanehisa, M., A database for post-genome analysis, Trends Genet., 13:375{376, 1997.
[4] Sato, K., Katsurada, T., Kimura, Y. and Kanehisa, M., Integrated GENES Database in KEGG,
Genome Informatics 1997, 334{335, 1997.

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