The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts.

Abstract

Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein-protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group.

Full text

Page 1

Published online 18 December 2007Nucleic Acids Research, 2008, Vol. 36, Database issueD793–D799
doi:10.1093/nar/gkm999
The H-Invitational Database (H-InvDB),
a comprehensive annotation resource for
human genes and transcripts?
Received September 16, 2007; Revised October 20, 2007; Accepted October 22, 2007
ABSTRACT
Here we report the new features and improvements
in our latest release of the H-Invitational Database
(H-InvDB; http://www.h-invitational.jp/), a compre-
hensive annotation resource for human genes and
transcripts. H-InvDB, originally developed as an
integrated database of the human transcriptome
based on extensive annotation of large sets of full-
length cDNA (FLcDNA) clones, now provides annota-
tion for 120558 human mRNAs extracted from the
International Nucleotide
(INSD), in addition to 54978 human FLcDNAs, in the
latestreleaseH-InvDB_4.6.Wemappedthosehuman
transcripts onto the human genome sequences
(NCBI build 36.1) and determined 34699 human
gene clusters, which could define 34057 (98.1%)
protein-coding and 642 (1.9%) non-protein-coding
loci; 858 (2.5%) transcribed loci overlapped with
predicted pseudogenes. For all these transcripts and
genes,weprovidecomprehensiveannotationinclud-
ing gene structures, gene functions, alternative
splicingvariants, functional
RNAs, functional domains, predicted sub cellular
localizations, metabolic pathways, predictions of
protein 3D structure, mapping of SNPs and micro-
satellite repeat motifs, co-localization with orphan
diseases, gene expression profiles, orthologous
genes, protein–protein interactions (PPI) and anno-
tation for gene families. The current H-InvDB annota-
tion resources consist of two main views: Transcript
view and Locus view and eight sub-databases: the
DiseaseInfoViewer,H-ANGEL,
Viewer, G-integra, the TOPO Viewer, Evola, the PPI
view and the Gene family/group.
SequenceDatabases
non-protein-coding
theClustering
INTRODUCTION
Human transcripts represent a biologically and function-
ally rich format for examining the structure of human
genes and alternative splicing isoforms. In particular,
cloning and sequencing of full-length cDNAs (FLcDNAs)
that cover all exons but no introns can facilitate the
precise determination of human gene structure (1). Studies
on human transcripts have thus been systematically and
extensively carried out to draw the outline of the human
transcriptome (2–6). The human transcriptome consists
of protein-coding mRNAs and non-coding functional
RNAs. Analysis of these sequences will provide insights
into how genomic information is transformed into higher
order biological phenomena. By comparative analysis of
the transcriptome with the human genome, we will be able
to determine the transcribed regions of the genome and
better understand the regulatory machinery of transcrip-
tion (7, 8). It is therefore of great significance to collect
information about human transcripts as well as their
annotations. We thus held the first international workshop
entitled ‘Human Full-length
Invitational’ (abbreviated as H-Invitational or H-Inv) in
Tokyo, Japan from 25th August to 3rd September 2002,
and constructed a novel, integrative database of the
human transcriptome, called H-InvDB (9,10). This con-
sists of the annotation of 42421 human FLcDNAs,
collected from six high-throughput producers of human
FLcDNAs in the world human gene collections.
To cover the increased number of human FLcDNAs
since the initial release of H-InvDB, we held the second
international annotation meeting entitled ‘H-Invitational
2 Functional Annotation Jamboree’ (abbreviated as
H-Invitational 2 or H-Inv2) in Tokyo, Japan from 15th
to 20th November 2003. The second major release of
H-InvDB (release 2.0) was based on the annotation
carried out at the H-Inv2 annotation jamboree. After
H-Inv2, we initiated the Genome Information Integration
Project (GIIP) and held the third and fourth annotation
meetings in October 2005 and October 2006. The products
of those two annotation meetings comprised releases 3.0
and 4.0 of H-InvDB. The increases in the number of
entries in H-InvDB are summarized in Table 1.
cDNA Annotation
THE ANNOTATION IN OUR LATEST UPDATE,
H-InvDB 2007
In our latest release H-InvDB_4.6, we annotated 120558
human mRNAs extracted
Nucleotide Sequence Databases (INSD) in addition to
54978 human FLcDNAs that were available on 15th June
2006. We mapped those human transcripts onto the human
genome sequences (NCBI build 36.1) and determined
34699 human gene clusters, which could define 34057
fromthe International
*A complete list of authors appears at the end of this article.
? 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/
by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Page 2

(98.1%) protein-coding and 643 (1.9%) non-protein-
coding loci, while 858 (2.5%) transcribed loci overlapped
with predicted pseudogenes. We basically followed the
mapping technique we described previously (9,10). We
updated annotation for the mitochondrial transcripts since
the previous major release, H-InvDB_4.0, which resulted
in a slightly decreased number for the transcripts and
clusters. Then we assigned a standardized functional
annotation to each H-Inv transcript by human curation,
based on the results of similarity searches and InterPro-
Scan (11). The numbers of manually curated human
proteins in each category are summarized in Table 2.
For these transcripts and genes, we provide compre-
hensive annotation including descriptions of their gene
structures, alternative splicing isoforms, functional non-
protein-coding RNAs, functional domains of proteins,
predicted sub cellular localizations, metabolic pathways,
predictions of protein 3D structure, mapping of SNPs and
microsatellite repeat motifs, co-localization with orphan
diseases, gene-expression profiles, orthologous genes and
evolutionary features in model animals, protein–protein
interaction (PPI) and annotation for gene families. We
have also annotated several new features related to
transcript quality.
NEW ANNOTATED FEATURES IN H-InvDB
Classification of ncRNA
We annotated the transcripts that do not have homology to
known protein-coding genes or InterPro-domain-containing
genes as non-protein-coding transcript candidates. We
classified1216 non-protein-coding
‘Identical to known ncRNA’ (124), ‘Similar to known
ncRNA’ (74) and ‘Putative ncRNA’ (1018) by homology
with known ncRNA databases
analysis
transcriptsinto
and discrimination
Sequencequalityfeatures:nonsense-mediateddecay(NMD),
read-through, reverse orientation
A total of 269 transcripts were annotated as candidates of
read-through and 2731 as targets of NMD by the extended
sequence quality annotation.
Category VII: pseudogenecandidates
To annotate transcribed pseudogene candidates, we did
the following: First, we filtered out the functional protein-
coding genes by only targeting representative category II
transcripts and those identified to have frame shifts and/or
nonsense mutations; Second, we predicted transcribed
pseudogene candidates based on a support vector machine
(SVM) method. In the current release, we annotated 1112
transcribed pseudogene candidates (Category VII).
Annotation ofgene families/groups
We annotated four selected gene families/groups: T-cell
receptor(TCR),Immunoglobulin
HistocompatibilityComplex
Leukocyte Antigen (HLA) and Olfactory receptor (OR)
using the original pipeline based on sequence analysis
against genome and protein databases complemented by a
text-mining approach. In the current release, we identified
15 TCR, 21 Ig, 72 MHC and 122 OR gene clusters.
All the annotation items and features of H-Inv
transcript sequences are stored and shown in the main
views or sub-databases in H-InvDB.
(Ig),
or
Major
Human(MHC)
COMPREHENSIVE ANNOTATION RESOURCES IN
H-InvDB
The current H-InvDB annotation resources consist of two
main views, Transcript view and Locus view, and eight
sub-databases: the DiseaseInfo Viewer, H-ANGEL, the
Clustering Viewer, G-integra, the TOPO Viewer, Evola,
the PPI view and the Gene family/group view with
the appropriate cross-links. An overview of the compre-
hensive annotation resources of the human gene and
transcripts in H-InvDB is shown in Figure 1.
Table 1. Statistics of H-InvDB entries
H-InvDB releaseDate of
release
Number of
transcripts
(HIT)
Number
of gene
clusters (HIX)
Number of
proteins (HIP)
Human genomeDate of
sequence
data-fix
1.0
2.0
3.0
4.0
4.6
2004/4/20
2005/8/31
2006/3/31
2007/3/30
2007/9/27
41118
56419
167992
175542
175536
21037
25585
35005
34701
34699
–
–
–
116228
116142
NCBI build 34.1
NCBI build 34.1
NCBI build 35.1
NCBI build 36.1
NCBI build 36.1
2002/7/15
2003/9/1
2005/3/1
2006/6/15
2006/6/15
Table 2. Statistics of manually curated representative H-Inv proteins
CategoryDefinition Number of
representative
HITs
%
I Identical to knownahuman
protein (?98% identity, =100%
coverage)
Similar to knownaprotein (?50%
identity, ?50% coverage)
InterPro domain
protein
Conserved hypothetical protein
Hypothetical protein
Hypothetical short protein (20–79
amino acids)
Pseudogene candidates
12404 36.42
II
31659.29
III containing30568.97
IV
V
VI
4210
5124
5250
12.33
15.05
15.42
VII
Total
8582.52
10034057
a‘Known’ proteins are experimentally validated proteins in literatures.
D794
Nucleic Acids Research, 2008, Vol. 36, Databaseissue

Page 3

Transcript view
The transcript view shows all the annotation of the H-Inv
transcript in 12 section tabs: (i) gene structure, (ii) gene
function,(iii)geneontology,(iv)predictedCDS,
(v) functional motif, (vi) sub cellular localization, (vii)
protein structure information, (viii) gene expression, (ix)
disease/pathology, (x) evolutionary information, (xi)
polymorphism(SNP,indel andmicrosatellite)and
Figure 1. H-InvDB: overview of the comprehensive annotation resource for the human genes and transcripts. The current H-InvDB annotation
resources consist of two main views, Transcript view and Locus view, and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering
Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group view. The Transcript view and the Locus view are the main
viewers to display the annotation of each H-Invitational transcript (HIT) and H-Invitational cluster (HIX). The DiseaseInfo Viewer, H-ANGEL, the
Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group view are sub-databases to provide detailed
annotation for each annotation feature. The links to related databases are provided from the appropriate viewers.
Nucleic Acids Research, 2008,Vol. 36,Database issue D795

Page 4

interspersed repeat information and (xii) transcript and
sequence quality information. As seen in the example of a
transcript view shown in Figure 1, this view also has links
to many external public databases including DDBJ/
EMBL/GenBank,RefSeq,
InterPro, Ensembl, EntrezGene, PubMed, dbSNP, GO
and GTOP and to web sites of the original data producers
of the FLcDNA clones and sequences including the
Chinese National Human Genome Center (CHGC),
GermancDNA Consortium
Research Institute, Inc. (HRI), the Institute of Medical
Science in the University of Tokyo (IMSUT), the Kazusa
DNA Research Institute (KDRI), the Mammalian Gene
Collection (MGC/NCI) and NEDO. This view was
previously known as the cDNA view (mRNA view).
UniProtKB,HGNC,
(DKFZ/MIPS),Helix
Locusview
The Locus view shows all the annotation of a locus in six
section tabs: (i) gene structure and location in the human
genome, (ii) gene function, (iii) alternative splicing pattern,
(iv) gene expression, (v) disease/pathology and (vi) cluster
member information. As seen in the example of a Locus
view shown in Figure 1, it shows links to external public
databases including DDBJ/EMBL/GenBank, RefSeq,
EntrezGene, GeneCards, HGNC and OMIM.
DiseaseInfo Viewer
The DiseaseInfo Viewer is a database of known and
orphan genetic diseases and their relation to H-Inv
clusters with EntrezGene and OMIM cross-links. The
DiseaseInfo Viewer provides two kinds of disease infor-
mation related to H-Inv clusters: known disease-related
genes and co-localized orphan diseases. An orphan disease
is defined as a disease mapped on a chromosomal region,
but for which the responsible gene has not been identified
yet. Co-localization does not necessarily mean a direct
relationship between gene and disease; however, genes
that are cytogenetically co-localized with a disease
could be possible candidate genes for that disease. The
co-localized H-Inv clusters are chosen by computing the
physical range of each cytogenetic band with a 1Mbp
margin.
Humananatomic geneexpression library (H-ANGEL)
H-ANGEL is a database of expression patterns that we
constructed to obtain a broad outline of such patterns for
human genes (12). We collected gene-expression data
in normal and adult human tissues that were generated by
three types of methods and in seven different platforms,
including: iAFLP, a PCR-based quantitative expression
profiling method; DNA arrays (long oligomers, short
oligomers and cDNA microarrays); and cDNA sequence
tags (SAGE, EST, BodyMap and MPSS). The H-ANGEL
database comprises the largest and most comprehensive
collection of gene expression patterns so far, which also
provides a classification of human genes in terms of their
expression.
Clustering Viewer
The Clustering Viewer facilitates the comparisons of
different clustering. It allows users to see whether H-Inv
transcripts are consistently clustered by different clustering
methods. It also displays multiple alignments of tran-
scripts by using CLUSTALW (13). The Clustering Viewer
shows all the member transcripts of an H-Inv cluster to
which a query sequence belongs.
G-integra
G-integra is an integrated genome browser, in which we
can examine the genomic structures of the transcripts. As
seen in an example view in Figure 1, the location in the
human genome and gene structure of H-Inv transcript
(green), and the corresponding RefSeq and Ensembl
entries are shown. The structures of the genes and
transcripts for 11 non-human species, Pan troglodytes
(chimpanzee), Macaca sp. (macaque), Mus musculus
(mouse), Rattus norvegicus (rat), Canis familiaris (dog),
Bos taurus (cow), Monodelphis domestica (opossum),
Gallusgallus (chicken),
Tetraodon nigroviridis (tetraodon) and Takifugu rubripes
(fugu) can be optionally displayed for comparison. Other
options allow the, the results of gene prediction programs
such as GenScan (14), HMMgene (15), FGENESH (16)
and JIGSAW (17) to be displayed.
Daniorerio(zebrafish),
TOPO Viewer
The TOPO Viewer is a tool for viewing subcellular
targeting signals predicted by TargetP (18) and the
presence of transmembrane helices predicted by SOSUI
(19) and TMHMM(20). The probabilities that a protein
may be delivered to up to nine distinct sub cellular
locations are predicted by WoLF PSORT (21). TargetP
predicts whether a protein contains a signal peptide, a
mitochondrial targeting signal or any other type of signal.
The TOPO Viewer consists of four tab pages: TABLE,
MAP, FILE and GFP. The TABLE tab page displays the
prediction results for all the programs used.
Evola
Evola is a database of evolutionary annotation of human
genes (22). It provides sequence alignments and phyloge-
netic trees of manually curated orthologous genes among
human and 11 model organisms, Pan troglodytes (chim-
panzee), Macaca sp. (macaque), Mus musculus (mouse),
Rattus norvegicus (rat), Canis familiaris (dog), Bos taurus
(cow), Monodelphis domestica (opossum), Gallus gallus
(chicken), Danio rerio (zebra fish), Tetraodon nigroviridis
(tetraodon) and Takifugu rubripes (fugu). Sequence
alignments and phylogenetic trees of the orthologous
genes and homologous genes are shown in Evola.
PPI view
The PPI view displays H-InvDB human PPI information
at http://www.jbirc.aist.go.jp/hinv/ppi/. We collected PPI
data from five databases; BIND, DIP, MINT, HPRD and
IntAct, removed redundancies of the PPI data among the
D796
Nucleic Acids Research, 2008, Vol. 36, Databaseissue

Page 5

databases based on their sequence similarities and
integrated them with the H-Invitational proteins.
Gene family/Group view
The Gene family/Group view provides human-curated
annotation datasets for the selected gene families/groups
at http://www.jbirc.aist.go.jp/hinv/ahg-db/geneFamily
Index.jsp. For H-InvDB release 4.0, we provided detailed
annotations for four selected gene families/groups: TCR,
Ig, MHC and OR. Each page provides the list of genes,
gene names, definitions and links for the appropriate
H-InvDB views.
H-InvDB New Identifier
We defined and assigned a unique identifier for each
annotation unit, transcript, protein or cluster (7,8). The
identifier for H-Invitational transcript is ‘HIT’, prefix HIT
plus nine digit numbers (e.g. HIT000000001) and for
H-Invitational cluster is ‘HIX’, prefix HIX plus seven digit
numbers (e.g. HIX0000001). In order to identify the
modification in sequence or annotation of an H-Inv entry,
a version is assigned to each ID and always stated with the
ID. Additionally, we now provide a new identifier for each
H-Invitational protein, ‘HIP’, prefix HIP with nine digit
numbers (e.g. HIP000000001).
H-InvDB Data Availability
H-InvDB is freely available for both academic and
commercial use and can be accessed online at http://
www.h-invitational.jp/(or hinv.jp). Annotated data can
also be downloaded in FASTA sequence files, the original-
format flat files or XML files at HTTP and FTP servers.
Themirror databaseis
hinvdb.ddbj.nig.ac.jp/. Minor updates are released every
three months and major updates are released once a year.
alsoavailable at http://
ACKNOWLEDGEMENTS
We acknowledge all the members of the H-Invitational 2
consortium and Genome Information Integration Project
(GIIP), especially the staffs of JBIRC for construction of
H-InvDB, Ryo Aono, Tomohiro Endo, Yukie Makita,
Hiromi Kubooka, Yuji Shinso, Harutoshi Maekawa,
Yasuhiro Fukunaga, Hajime Nakaoka, Yoshito Ueki,
Yoshihide Mimiura, Ryuzou Matsumoto, Seigo Hosoda,
Yo Takahashi, Taichirou Sugisaki,
Hiroaki Kawashima, Yasuhiro Imamizu, Makoto Ogawa
for their technical assistance. This research is financially
supported by the Ministry of Economy, Trade and
Industry of Japan (METI), the Ministry of Education,
Culture, Sports, Science and Technology of Japan
(MEXT) andtheJapan
Consortium (JBIC). Also, this work is partly supported
by the Research Grant for the RIKEN Genome
Exploration Research Project from MEXT to Y.H. and
the Grant for the RIKEN Frontier Research System,
Functional RNA research program. Funding to pay the
Hiroki Hokari,
BiologicalInformatics
Open Access publication charges for this article was
provided by JBIC.
Conflict of interest statement. None declared.
REFERENCES
1. Ota,T. et al. (1997) Full-length cDNA project toward a high
throughput functional analysis. Microb. Comp. Genomics, 2,
204–205.
2. Yudate,H.T. et al. (2001) HUNT: launch of a full-length cDNA
database from the helix research institute. Nucleic Acids Res., 29,
185–188.
3. Wiemann,S. et al. (2001) Toward a catalog of human genes and
proteins: sequencing and analysis of 500 novel complete protein
coding human cDNAs. Genome Res., 11, 422–435.
4. Strausberg,R.L. et al. (2002) Generation and initial analysis of more
than 15,000 full-length human and mouse cDNA sequences. Proc.
Natl Acad. Sci. USA, 99, 16899–16903.
5. Kikuno,R. et al. (2002) HUGE: a database for human large
proteins identified in the Kazusa cDNA sequencing project. Nucleic
Acids Res., 30, 166–168.
6. Carninci,P. et al. (2005) The transcriptional landscape of the
mammalian genome. Science, 309, 1559–1563.
7. Frith,M.C. et al. (2006) Pseudo-messenger RNA: phantoms of the
transcriptome. PLoS Genet, 2, p. e23.
8. Gingeras,T.R. et al. (2007) Origin of phenotypes: genes and
transcripts. Genome Res., 17, 682–690.
9. Imanishi,T. et al. (2004) Integrative annotation of 21,037
human genes validated by full-length cDNA clones. PLoS Biol., 2,
856–875.
10. Yamasaki,C. et al. (2005) Investigation of protein
functions through data-mining on integrated human
transcriptome database, H-Invitational database (H-InvDB). Gene,
364, 99–107.
11. Mulder,N.J. et al. (2007) New developments in the
InterPro database. Nucleic Acids Res., 35(Database issue),
D224–D228.
12. Tanino,M. et al. (2005) The human anatomic gene expression
library (H-ANGEL), the H-Inv integrative display of human gene
expression across disparate technologies and platforms. Nucleic
Acids Res., 33(Database Issue), D567–D572.
13. Thompson,J.D., Higgins,D.G. and Gibson,T.J. (1994) CLUSTAL
W: improving the sensitivity of progressive multiple sequence
alignment through sequence weighting, position-specific gap
penalties and weight matrix choice. Nucleic Acids Res., 22,
4673–4680.
14. Burge,C. and Karlin,S. (1997) Prediction of complete gene
structures in human genomic DNA. J. Mol. Biol., 268, 78–94.
15. Krogh,A. (1997) Two methods for improving performance of an
HMM and their application for gene finding. Proc. Int. Conf. Intell.
Syst. Mol. Biol., 5, 179–186.
16. Salamov,A.A. and Solovyev,V.V. (2000) Ab initio gene finding in
Drosophila genomic DNA. Genome Res., 10, 516–522.
17. Allen,J.E. and Salzberg,S.L. (2005) JIGSAW: integration of
multiple sources of evidence for gene prediction. Bioinformatics, 21,
3596–3603.
18. Emanuelsson,O. et al. (2000) Predicting subcellular localization of
proteins based on their N-terminal amino acid sequence. J. Mol.
Biol., 300, 1005–1016.
19. Hirokawa,T., Boon-Chieng,S. and Mitaku,S. (1998) SOSUI: classi-
fication and secondary structure prediction system for membrane
proteins. Bioinformatics, 14, 378–379.
20. Krogh,A. et al. (2001) Predicting transmembrane protein topology
with a hidden Markov model: application to complete genomes.
J. Mol. Biol., 305, 567–580.
21. Horton,P. et al. (2007) WoLF PSORT: protein localization
predictor. Nucleic Acids Res., 35(Web Server issue), W585–W587.
22. Matsuya,A. et al. (2008) Evola: ortholog database of all human
genes in H-InvDB with manual curation of phylogenetic trees.
Nucleic Acids Res, (in press).
Nucleic Acids Research, 2008,Vol. 36,Database issueD797

Page 6

LIST OF AUTHORS FOR THE GENOME
INFORMATION INTEGRATION PROJECT AND
H-INVITATIONAL 2 CONSORTIUM
Chisato Yamasaki1,2, Katsuhiko Murakami1,2,
Yasuyuki Fujii3, Yoshiharu Sato1,2, Erimi Harada1,2,
Jun-ichi Takeda1,2, Takayuki Taniya1,2,
Ryuichi Sakate1,2, Shingo Kikugawa1,2,
Makoto Shimada1,2, Motohiko Tanino4,
Kanako O. Koyanagi5, Roberto A. Barrero6,
Craig Gough1,2, Hong-Woo Chun1,2,
Takuya Habara1, Hideki Hanaoka7,
Yosuke Hayakawa1,8, Phillip B. Hilton1,2,
Yayoi Kaneko9, Masako Kanno1,2,
Yoshihiro Kawahara1,2, Toshiyuki Kawamura10,
Akihiro Matsuya1,11, Naoki Nagata12,
Kensaku Nishikata1,13, Akiko Ogura Noda1,2,
Shin Nurimoto14, Naomi Saichi1,2,
Hiroaki Sakai15, Ryoko Sanbonmatsu1,2,
Rie Shiba1,2, Mami Suzuki1,2,
Kazuhiko Takabayashi8, Aiko Takahashi1,2,
Takuro Tamura16, Masayuki Tanaka1,2,
Susumu Tanaka17, Fusano Todokoro1,18,
Kaori Yamaguchi1, Naoyuki Yamamoto1,19,
Toshihisa Okido20, Jun Mashima20,
Aki Hashizume20, Lihua Jin20, Kyung-Bum Lee20,
Yi-Chueh Lin20, Asami Nozaki20,
Katsunaga Sakai20, Masahito Tada20,
Satoru Miyazaki21, Takashi Makino22,
Hajime Ohyanagi20,23, Naoki Osato20,
Nobuhiko Tanaka20, Yoshiyuki Suzuki20,
Kazuho Ikeo20, Naruya Saitou24,
Hideaki Sugawara20, Claire O’Donovan25,
Tamara Kulikova25, Eleanor Whitfield25,
Brian Halligan26, Mary Shimoyama26,
Simon Twigger26, Kei Yura27,
Kouichi Kimura28, Tomohiro Yasuda28,
Tetsuo Nishikawa28,29, Yutaka Akiyama30,
Chie Motono30, Yuri Mukai30,
Hideki Nagasaki15,30, Makiko Suwa30,
Paul Horton30, Reiko Kikuno31, Osamu Ohara31,
Doron Lancet32, Eric Eveno33,34,
Esther Graudens33,34, Sandrine Imbeaud33,34,35,
Marie Anne Debily33,34,36,
Yoshihide Hayashizaki37,38, Clara Amid39,
Michael Han39, Andreas Osanger39,
Toshinori Endo5, Michael A. Thomas40,
Mika Hirakawa41, Wojciech Makalowski42,
Mitsuteru Nakao43, Nam-Soon Kim44,
Hyang-Sook Yoo44, Sandro J. De Souza45,
Maria de Fatima Bonaldo46,
Yoshihito Niimura47, Vladimir Kuryshev48,
Ingo Schupp48, Stefan Wiemann48,
Matthew Bellgard6, Masafumi Shionyu49,
Libin Jia50, Danielle Thierry-Mieg51,
Jean Thierry-Mieg51, Lukas Wagner51,
Qinghua Zhang34,52, Mitiko Go53,
Shinsei Minoshima54, Masafumi Ohtsubo54,
Kousuke Hanada55, Peter Tonellato56, Takao Isogai29,
Ji Zhang34,57, Boris Lenhard58, Sangsoo Kim59,
Zhu Chen34,60,61, Ursula Hinz62, Anne Estreicher62,
Kenta Nakai63, Izabela Makalowska64,
Winston Hide65, Nicola Tiffin65,
Laurens Wilming66, Ranajit Chakraborty67,
Marcelo Bento Soares68, Maria Luisa Chiusano69,
Yutaka Suzuki70, Charles Auffray33,34,
Yumi Yamaguchi-Kabata2, Takeshi Itoh2,15,
Teruyoshi Hishiki2, Satoshi Fukuchi20,
Ken Nishikawa20, Sumio Sugano2,70, Nobuo Nomura2,
Yoshio Tateno20, Tadashi Imanishi2,5,yand
Takashi Gojobori2,20
1Japan Biological Information Research Center, Japan
Biological Informatics Consortium,2Biological
Information Research Center, National Institute of
Advanced Industrial Science and Technology, Tokyo,
3Graduate School Medicine, Dentistry and
Pharmaceutical Sciences, Okayama University, Okayama,
4DNA Chip Research Inc., Kanagawa,5Hokkaido
University, Hokkaido, Japan,6Centre for Comparative
Genomics, Murdoch University, WA, Australia,
7Biotechnology Research Center, The University of
Tokyo,8Hitachi Software Engineering Co., Ltd.,
9Mitsubishi Kagaku Institute of Life Sciences,10Fujitsu
Limited, Tokyo,11Hitachi, Co., Ltd., Saitama,12Japan
Science and Technology Agency,13NEC Soft, Ltd.,
14Mitsui Knowledge Industry Co., Ltd, Tokyo,15National
Institute of Agrobiological Sciences, Ibaraki,16BITS Co.,
Ltd., Shizuoka,17Tokyo Institute of Psychiatry, Tokyo,
18DYNACOM Co., Ltd., Chiba,19C’s Lab Co., Ltd.,
Hokkaido,20Center for Information Biology and DNA
Data Bank of Japan, National Institute of Genetics,
Shizuoka,21Tokyo University of Science, Chiba, Japan,
22University of Dublin, Trinity College, Dublin, Ireland,
23Mitsubishi Space Software Co., Ltd., Ibaraki,24Division
of Population Genetics, National Institute of Genetics,
Shizuoka, Japan,25EMBL Outstation-Hinxton, European
Bioinformatics Institute, Cambridge, UK,
26Bioinformatics Research Center, Medical College of
Wisconsin, WI, USA,27Center for Computational Science
and Engineering, Japan Atomic Energy Agency, Kyoto,
28Central Research Laboratory, Hitachi Ltd.,29Reverse
Proteomics Research Institute, CO., Ltd.,
30Computational Biology Research Center, National
Institute of Advanced Industrial Science and Technology,
Tokyo,31Department of Human Gene, Kazusa DNA
Research Institute, Chiba, Japan,32Department of
Molecular Genetics, Weizmann Institute of Science,
Rehovot, Israel,33Genexpres, Functional Genomics and
Systems Biology for Health (CNRS and Pierre & Marie
Curie University - Paris VI), Villejuif, France,
34Sino-French Laboratory in Life Sciences and Genomics,
Shanghai, China,35Centre de Ge ´ ne ´ tique Mole ´ culaire,
CNRS and Gif/Orsay DNA Microarray Platform, Gifs/
Yvette,36Laboratory of Genomes Functional
Exploration, CEA, DSV, IRCM, Evry, France,
37Genomic Sciences Center, RIKEN Yokohama Institute,
Kanagawa,38Genome Science Laboratory, Discovery and
Research Institute, RIKEN Wako Institute, Saitama,
Japan,39GSF - National Research Center for
Environment and Health, Institute for Bioinformatics,
D798
Nucleic Acids Research, 2008, Vol. 36, Databaseissue

Page 7

Neuherberg, Germany,40IdahoStateUniversity,ID,USA,
41Institute for Chemical Research, Kyoto University,
Kyoto, Japan,42Institute of Bioinformatics, University of
Muenster, Muenster, Germany,43Kazusa DNA Research
Institute, Chiba, Japan,44Korea Research Institute of
Bioscience & Biotechnology, Taejeon, Korea,45Ludwig
Institute for Cancer Research, Sao Paulo, Brazil,
46Medical Education and Biomedical Research Facility,
University of Iowa, IA, USA,47Medical Research
Institute, Tokyo Medical and Dental University, Tokyo,
Japan,48Molecular Genome Analysis, German Cancer
Research Center, Heidelberg, Germany,49Nagahama
Institute of Bio-Science and Technology, Shiga, Japan,
50National Cancer Institute, National Institutes of Health,
MD,51National Center for Biotechnology Information,
National Library of Medicine, National Institutes of
Health, MD, USA,52National Engineering Center for
Biochips at Shanghai, Shanghai, China,53Ochanomizu
University, Tokyo,54Photon Medical Research Center,
Hamamatsu University School of Medicine, Shizuoka,
55Plant Science Center, RIKEN Yokohama Institute,
Kanagawa,56Harvard Medical School, MA, USA,
57Shanghai Institutes for Biological Sciences, Chinese
Academy of Sciences, Shanghai, China,58Center for
Genomics and Bioinformatics, Karolinska Institute,
yTo whom correspondence should be addressed. Tel: +81-3-3599-8800;
Fax: +81-3-3599-8801; E-mail: t.imanishi@aist.go.jp
Correspondence may also be addressed to Takashi Gojobori. Tel: +81-
55-981-6847; Fax: +81-55-981-6848; Email: tgojobor@genes.nig.ac.jp
Stockholm, Sweden,59Soongsil University, Seoul, Korea,
60State Key Laboratory of Medical Genomics, Shanghai
Institute of Hematology, Rui Jin Hospital, Shanghai Jiao
Tong University School of Medicine,61Chinese National
Human Genome Center at Shanghai, Shanghai, China,
62Swiss Institute of Bioinformatics, Geneva, Switzerland,
63The Institute of Medical Science, The University of
Tokyo, Tokyo, Japan,64The Pennsylvania State
University, PA, USA,65The South African National
Bioinformatics Institute, University of Western Cape,
Cape Town, South Africa,66The Wellcome Trust Sanger
Institute, Wellcome Trust Genome Campus, Cambridge,
UK,67University of Cincinnati, OH,68Children’s
Memorial Research Center, Northwestern University,
Feinberg School of Medicine, USA,69University of
Naples ‘‘Federico II’’, Naples, Italy and70Department of
Medical Genome Sciences, Graduate School of Frontier
Sciences, The University of Tokyo, Tokyo, Japan
Nucleic Acids Research, 2008,Vol. 36,Database issueD799