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n\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg1}{\bkmkend Pg1}\par\pard
\ql \li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\
ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql
\li2268\sb16\sl-241\slmult0 \up0 \expndtw-9\charscalex91 \ul0\nosupersub\cf1\f2\
fs21 TissueDB: A database of adult human anatomy and histology. \par\pard\qj \li
2268\sb0\sl-430\slmult0 \par\pard\qj\li2268\ri2042\sb33\sl-430\slmult0 \up0 \exp
ndtw-9\charscalex89 Osamu Ogasawara\ul0\super\cf2\f3\fs20 1,2\ul0\nosupersub\cf1
\f2\fs21 , Tatsuya Nishizawa\ul0\super\cf2\f3\fs20 2\ul0\nosupersub\cf1\f2\fs21
, Duo Wang\ul0\super\cf2\f3\fs20 2\ul0\nosupersub\cf1\f2\fs21 , Yumiko Harumiya\
ul0\super\cf2\f3\fs20 2\ul0\nosupersub\cf1\f2\fs21 , \up0 \expndtw-9\charscalex9
3 Fuuko Matsuda\ul0\super\cf2\f3\fs20 2\ul0\nosupersub\cf1\f2\fs21 , Midori Sash
ida\ul0\super\cf2\f3\fs20 2\ul0\nosupersub\cf1\f2\fs21 , Lu Yao\ul0\super\cf2\f3
\fs20 1\ul0\nosupersub\cf1\f2\fs21 , Takako Takai-Igarashi\ul0\super\cf2\f3\fs20
1\ul0\nosupersub\cf1\f2\fs21 and \up0 \expndtw-9\charscalex88 Toshihisa Takagi
\ul0\super\cf2\f3\fs20 1 \par\pard\qj \li2268\ri2034\sb402\sl-440\slmult0 \up0 \
expndtw-9\charscalex93 1\ul0\nosupersub\cf1\f2\fs21 Laboratory of Genome Databas
e, Human Genome Center, The Institute of \up0 \expndtw-9\charscalex89 Medical Sc
ience \par\pard\ql \li2268\sb145\sl-241\slmult0 \up0 \expndtw-9\charscalex86 The
University of Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan \par\pard\qj \l
i2268\sb0\sl-420\slmult0 \par\pard\qj\li2268\ri3949\sb52\sl-420\slmult0 \up0 \ex
pndtw-9\charscalex90 \ul0\super\cf2\f3\fs20 2\ul0\nosupersub\cf1\f2\fs21 Informa
tion and Mathematical Science Laboratory Inc. \up0 \expndtw-9\charscalex85 2-43-
1, Ikebukuro, Toshima-ku, Tokyo, Japan \par\pard\ql \li2268\sb0\sl-253\slmult0 \
par\pard\ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb0\sl-253\slmult0 \pa
r\pard\ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb6\sl-253\slmult0 \up0
\expndtw-9\charscalex100 \ul0\nosupersub\cf3\f4\fs22 Abstract \par\pard\qj \li22
68\ri2026\sb24\sl-427\slmult0 \up0 \expndtw-10\charscalex94 We have developed an
internet-accessible database, TissueDB, which \line \up0 \expndtw-10\charscalex
92 provides a hierarchy of names and synonyms for adult human tissues. \line \up
0 \expndtw-10\charscalex95 There are two goals for TissueDB. The first is to pro
vide a framework \line \up0 \expndtw-9\charscalex91 within which to store data c
oncerning gene expression, tissue sources of \line \up0 \expndtw-9\charscalex91
cultured cell lines, and other spatially organized data. The second goal \line \
up0 \expndtw-9\charscalex91 is to provide a dictionary of the anatomical and his
tological terms used \line \up0 \expndtw-9\charscalex92 for computational extrac
tion of information from biological texts. This \line \up0 \expndtw-10\charscale
x95 database focuses, therefore, on the structures of microscopic anatomy \line
\up0 \expndtw-10\charscalex94 and histology, and provides many synonyms fo
r each structure. \line \up0 \expndtw-10\charscalex90 TissueDB currently conta
ins 3,000 human body structures and 10,000 \line \up0 \expndtw-10\charscalex91 n
ames, including English and Latin synonyms. TissueDB also provides \line \up0 \e
xpndtw-9\charscalex94 the biological sources of cDNA libraries and cultured cell
lines. As so \line \up0 \expndtw-10\charscalex92 many gene expression phenom
ena have been studied using these \line \up0 \expndtw-10\charscalex94 mater
ials, an organized body of information on the tissues in which \line \up0 \expnd
tw-10\charscalex91 gene expression occurs is useful. \par\pard\qj \li2268\ri2026
\sb19\sl-420\slmult0 \up0 \expndtw-10\charscalex94 We have also collected gene e
xpression data from numerous scientific \line \up0 \expndtw-9\charscalex91 paper
s. We investigated 1,500 papers and collected gene expression data \line \up0 \e
xpndtw-10\charscalex91 on approximately 400 genes that are related to endocrine
phenomena.
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}}\par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart P
g2}{\bkmkend Pg2}\par\pard\ql \li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb0
\sl-253\slmult0 \par\pard\ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb211
\sl-253\slmult0 \up0 \expndtw-10\charscalex94 \ul0\nosupersub\cf3\f4\fs22 The da
tabase has an easy to use search interface and can be accessed \par\pard\li2268\
sb191\sl-253\slmult0\fi0\tx3192\tx4010\tx5347\tx6391\tx6998 \up0 \expndtw-8\char
scalex100 over\tab \up0 \expndtw-8\charscalex100 the\tab \up0 \expndtw-8\charsca
lex100 Internet\tab \up0 \expndtw-8\charscalex100 using\tab \up0 \expndtw-8\char
scalex100 a\tab \up0 \expndtw-8\charscalex100 WWW browser at\par\pard\ql
\li2268\sb163\sl-253\slmult0 \up0 \expndtw-10\charscalex90 {\field{\*\fldinst {
HYPERLINK "http://tissuedb.ontology.ims.u-tokyo.ac.jp/" }}{\fldrslt {\ul0\nosupe
rsub\cf3\f4\fs22 http://tissuedb.ontology.ims.u-tokyo.ac.jp}}} \par\pard\ql \li2
268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li226
8\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\
sb15\sl-253\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf3\f4\fs22 IN
TRODUCTION \par\pard\qj \li2268\ri2026\sb45\sl-425\slmult0 \up0 \expndtw-10\char
scalex93 In higher organisms, such as humans, cells are highly differentiated. \
line \up0 \expndtw-9\charscalex94 For example, cells differ in physiological fun
ction, in their signaling \line \up0 \expndtw-10\charscalex93 pathways and metab
olism, and in their gene expression patterns and \line \up0 \expndtw-10\charscal
ex94 responses to medicine. Even the gene function can differ among cells. \line
\up0 \expndtw-10\charscalex91 Glucocorticoid receptor \up0 \expndtw-10\charsca
lex93 (GR), for example, activates expression of \par\pard\qj \li2268\ri202
6\sb0\sl-430\slmult0 \up0 \expndtw-10\charscalex93 corticotropin releasing facto
r (CRF) in the placenta, but inhibits CRF \line \up0 \expndtw-10\charscalex92 ex
pression in the paraventricular nucleus. Thus, arrangement of such \line \up0 \e
xpndtw-10\charscalex94 knowledge in a database that includes essential informati
on on cells \line \up0 \expndtw-9\charscalex92 and tissues, as well as a referen
ce database of names, is something that \line \up0 \expndtw-10\charscalex92 is u
rgently needed. \par\pard\qj \li2268\ri2026\sb0\sl-430\slmult0 \up0 \expndtw-10\
charscalex90 A great deal of human gene expression data has already been collect
ed, \up0 \expndtw-10\charscalex89 and several excellent databases of gene expres
sion in humans have been \up0 \expndtw-10\charscalex97 developed (1-3). It is im
perative, however, that descriptions of gene \up0 \expndtw-10\charscalex97 expre
ssion locations be brought together, in order that comparisons \up0 \expndtw-9\c
harscalex100 between expression data can be made. Comparisons involving such \up
0 \expndtw-10\charscalex97 large amounts of data cannot possibly be undertaken w
ithout some \up0 \expndtw-10\charscalex91 automation using computer programs. \p
ar\pard\qj \li2268\ri2026\sb0\sl-420\slmult0 \up0 \expndtw-9\charscalex95 With r
egard to the above, therefore, the reference database for tissues \line \up0 \ex
pndtw-10\charscalex91 should satisfy the following requirements: \up0 \expnd
tw-10\charscalex88 (i) The anatomical and \par\pard\qj \li2268\ri2026\sb0\sl-
426\slmult0 \up0 \expndtw-10\charscalex93 histological data should cover the
whole body and be arranged \up0 \expndtw-9\charscalex89 hierarchically. (i
i) The reference database should focus not only on gross \up0 \expndtw-10\charsc
alex91 anatomy but also on microscopic anatomy and histology. (iii) The data \up
0 \expndtw-10\charscalex86 should be provided in a machine-readable form. \par\p
ard\qj \li2268\ri2026\sb0\sl-426\slmult0 \up0 \expndtw-10\charscalex96 In additi
on, a great deal of gene expression data are reported in the \line \up0 \expndtw
-8\charscalex100 abstracts of scientific papers. These data can be acquired by u
sing \line \up0 \expndtw-10\charscalex94 computer programs that analyze natural
language. In the subsequent \line \up0 \expndtw-10\charscalex95 text, however, v
arious terms are used to describe gene expression in
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15}}{\sp{\sn fLine}{\sv 0}}{\sp{\sn lineType}{\sv 0}}{\sp{\sn fArrowheadsOK}{\sv
1}}{\sp{\sn fBehindDocument}{\sv 1}}{\sp{\sn lineColor}{\sv 0}}
}}\par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart P
g3}{\bkmkend Pg3}\par\pard\qj \li2268\sb0\sl-430\slmult0 \par\pard\qj\li2268\ri2
026\sb394\sl-430\slmult0 \up0 \expndtw-9\charscalex92 \ul0\nosupersub\cf3\f4\fs2
2 tissue. Therefore, in order to extract gene expression data from the body \up0
\expndtw-9\charscalex91 of the text of scientific papers, a database that inclu
des many synonyms \up0 \expndtw-10\charscalex91 for the tissues is required. \pa
r\pard\ql \li2268\ri2026\sb0\sl-428\slmult0\tx3120 \up0 \expndtw-10\charscalex96
With this goal in mind, databases have been developed that offer a \line \up0 \
expndtw-9\charscalex100 comprehensive list of tissues with respect to the primat
e brain (4), \line \up0 \expndtw-10\charscalex89 mouse developmental anatomy (5,
6) and even human anatomy (7). \line \up0 \expndtw-9\charscalex94 Nevertheless,
there is, to date, no database that fulfills all the \line \up0 \expnd
tw-10\charscalex93 above-mentioned requirements. In particular, a database that
sets out \line \up0 \expndtw-9\charscalex94 histological relations is still lack
ing. Thus, we have created TissueDB. \line \up0 \expndtw-9\charscalex92 This dat
abase currently provides the following data: (i) A hierarchy of \line \up0 \expn
dtw-10\charscalex91 both anatomical terms and histological terms for the adult h
uman. (ii) \line \up0 \expndtw-10\charscalex91 Numerous synonyms for adult human
tissues. (iii) Biological sources of \line \up0 \expndtw-10\charscalex97 cDNA l
ibraries and cultured cell lines; as so many gene expression \line \up0 \expndtw
-10\charscalex90 phenomena have been studied using these materials, an organized
body \line \up0 \expndtw-9\charscalex90 of information on the tissues in which
gene expression occurs is needed. \line\tab \up0 \expndtw-10\charscalex96 We col
lected gene expression data from scientific papers. We \up0 \expndtw-10\charscal
ex94 investigated \up0 \expndtw-10\charscalex91 1,500 papers, and collected
gene expression data on \up0 \expndtw-10\charscalex89 approximately 400 genes
that are related to endocrine phenomena. \par\pard\ql \li2268\sb0\sl-253\slmult
0 \par\pard\ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb43\sl-253\slmult0
\up0 \expndtw-8\charscalex100 DATABASE CONTENTS \par\pard\ql \li2268\sb187\sl-2
53\slmult0 \up0 \expndtw-10\charscalex89 Anatomical and histological data \par\p
ard\qj \li2268\ri2026\sb21\sl-430\slmult0 \up0 \expndtw-10\charscalex91 TissueDB
provides a hierarchy of both the anatomical and histological \line \up0 \expndt
w-9\charscalex91 terms used to describe the objects of the adult human body. An
object is \line \up0 \expndtw-9\charscalex100 either a structural entity \up0 \e
xpndtw-8\charscalex100 (e.g., brain, femur and erythrocyte) or a \par\pard\qj \l
i2268\ri2026\sb0\sl-430\slmult0\tx3261 \up0 \expndtw-10\charscalex91 concept \ta
b \up0 \expndtw-10\charscalex93 (e.g., digestive system, connective tiss
ue and mucous \line \up0 \expndtw-10\charscalex93 membrane). The TissueID
and a term identifying the object are \line \up0 \expndtw-10\charscalex93
assigned to each object. Each object can be discriminated as a unique \line \up
0 \expndtw-10\charscalex94 item by means of these identifiers. English and Latin
synonyms have \line \up0 \expndtw-8\charscalex100 been collected for each objec
t. Currently, the database offers \up0 \expndtw-10\charscalex80 3,000 \par\pard\
ql \li2268\sb127\sl-253\slmult0 \up0 \expndtw-10\charscalex88 objects and 10,000
names. \par\pard\qj \li2268\ri2026\sb50\sl-420\slmult0 \up0 \expndtw-10\charsca
lex94 There are two parts to the hierarchy: the anatomical and the \li
ne \up0 \expndtw-10\charscalex95 histological hierarchy. Therefore, relations be
tween TissueDB objects \line \up0 \expndtw-9\charscalex92 are set up not as a tr
ee structure, but as a directed acyclic graph (DAG)
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{\sp{\sn shapeType}{\sv 0}}{\sp{\sn fFlipH}{\sv 0}}{\sp{\sn fFlipV}{\sv 0}}{\sp{
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{\sp{\sn fFillOK}{\sv 1}}{\sp{\sn fFilled}{\sv 1}}{\sp{\sn fillColor}{\sv 167772
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1}}{\sp{\sn fBehindDocument}{\sv 1}}{\sp{\sn lineColor}{\sv 0}}
}}\par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart P
g4}{\bkmkend Pg4}\par\pard\qj \li2268\sb0\sl-426\slmult0 \par\pard\qj\li2268\ri2
026\sb402\sl-426\slmult0 \up0 \expndtw-9\charscalex91 \ul0\nosupersub\cf3\f4\fs2
2 structure. The anatomical hierarchy is organized according to the \up0
\expndtw-9\charscalex89 systematic anatomy of the human body. The histol
ogical hierarchy \up0 \expndtw-10\charscalex97 divides tissues into four classe
s: epithelial, muscular, nervous, and \up0 \expndtw-10\charscalex93 supporting t
issues (Figure 1). \par\pard\qj \li2268\ri2026\sb19\sl-420\slmult0 \up0 \expndtw
-9\charscalex91 There are two kinds of relation between objects in TissueDB. The
first is \line \up0 \expndtw-9\charscalex100 what may be called a \up0 \expndtw
-10\charscalex93 part of \u8217?relation, which defines those relations \par\par
d\ql \li2268\sb158\sl-253\slmult0\tx9249 \up0 \expndtw-10\charscalex93 that pert
ain between structural entities. In TissueDB, the relation \tab \up0 \expndtw-10
\charscalex87 A is \par\pard\ql \li2268\sb167\sl-253\slmult0\tx3266\tx5056 \up0
\expndtw-10\charscalex90 part of B \tab \up0 \expndtw-10\charscalex95 is interpr
eted as \tab \up0 \expndtw-10\charscalex95 B is a lower structure of A\u8217?. \
par\pard\qj \li2268\ri2026\sb25\sl-426\slmult0 \up0 \expndtw-10\charscalex97 The
second relation between objects is that which pertains between \line \up0 \expn
dtw-10\charscalex94 concepts, or between an entity and a concept, and this is kn
own as a \line \up0 \expndtw-10\charscalex96 category \up0 \expndtw-10\charscale
x95 . For example, the digestive system is a lower category of the \line \up0 \e
xpndtw-10\charscalex87 human body, and the trunk is a lower structure of the hum
an body. \par\pard\ql \li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb0\sl-253\
slmult0 \par\pard\ql\li2268\sb71\sl-253\slmult0 \up0 \expndtw-10\charscalex90 Bi
ological sources of cDNA libraries and cultured cell lines \par\pard\qj \li2268\
ri2026\sb45\sl-425\slmult0 \up0 \expndtw-10\charscalex91 As so many gene express
ion phenomena have been studied using cDNA \line \up0 \expndtw-9\charscalex91 li
braries and cultured cell lines, TissueDB provides the biological \line
\up0 \expndtw-10\charscalex91 sources of the UniGene libraries and human cancer
cell lines provided \line \up0 \expndtw-10\charscalex90 by the American Type Cul
ture Collection (ATCC). The biological sources \line \up0 \expndtw-10\charscalex
90 are described using the TissueDB hierarchy. By using information from \line \
up0 \expndtw-10\charscalex90 the UniGene library sources, we can calculate in wh
ich tissue UniGene \line \up0 \expndtw-8\charscalex100 clusters are expressed.
The results of this calculation can be \line \up0 \expndtw-10\charscalex
89 downloaded from our Web site. \par\pard\ql \li2268\sb0\sl-253\slmult0 \par\pa
rd\ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb72\sl-253\slmult0 \up0 \ex
pndtw-10\charscalex94 Gene expression data \par\pard\qj \li2268\ri2026\sb23\sl-4
28\slmult0 \up0 \expndtw-10\charscalex92 TissueDB provides gene expression infor
mation on approximately 400 \line \up0 \expndtw-10\charscalex91 genes that are r
elated to endocrine phenomena. In addition to the gene \line \up0 \expndtw-10\ch
arscalex91 expression data, cases in which gene expression was undetectable have
\line \up0 \expndtw-9\charscalex92 also been collected. We investigated 1,500 s
cientific papers. The papers \line \up0 \expndtw-10\charscalex97 were chosen fro
m the references of textbooks or from review articles \line \up0 \expndtw-10\cha
rscalex88 about endocrinology. \par\pard\qj \li2268\sb0\sl-420\slmult0 \par\pard
\qj\li2268\ri2026\sb19\sl-420\slmult0 \up0 \expndtw-10\charscalex95 The expressi
on data have the following attributes: the LocusLink ID, \line \up0 \expndtw-10\
charscalex90 the LocusLink gene name, the article identifier of the PubMed datab
ase
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}}
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{\sp{\sn shapeType}{\sv 202}}{\sp{\sn fFlipH}{\sv 0}}{\sp{\sn fFlipV}{\sv 0}}{\s
p{\sn fRecolorFillAsPicture}{\sv 0}}{\sp{\sn fUseShapeAnchor}{\sv 0}}{\sp{\sn fL
ine}{\sv 0}}{\sp{\sn fFilled}{\sv 0}}{\sp{\sn fLayoutInCell}{\sv 1}}{\sp{\sn fBe
hindDocument}{\sv 1}}{\shptxt\pard\plain \qj\sl162 \li0\ri0 \expndtw-3\charscale
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\par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg5
}{\bkmkend Pg5}\par\pard\qj \li2268\sb0\sl-430\slmult0 \par\pard\qj\li2268\ri202
6\sb394\sl-430\slmult0 \up0 \expndtw-9\charscalex92 \ul0\nosupersub\cf3\f4\fs22
(PMID), the TissueID in which the gene expresses, and the \up0
\expndtw-10\charscalex89 experimental method used to study gene expression, suc
h as RT-PCR, in \up0 \expndtw-10\charscalex88 situ hybridization, immunohistoche
mistry, and so on (Figure 2). \par\pard\ql \li2268\sb0\sl-253\slmult0 \par\pard\
ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb71\sl-253\slmult0 \up0 \expnd
tw-6\charscalex100 IMPLEMENTATION \par\pard\ql \li2268\ri2026\sb23\sl-428\slmult
0 \up0 \expndtw-9\charscalex94 TissueDB is accessed via the Internet using
a web browser. The \line \up0 \expndtw-9\charscalex92 database can be searc
hed and the results accessed using Netscape 4.0 or \line \up0 \expndtw-10\charsc
alex92 Internet Explorer 4.0, or later versions of these programs. \line \up0 \e
xpndtw-10\charscalex94 TissueDB runs on a Sun server running the Solaris operati
ng system, \line \up0 \expndtw-10\charscalex94 and uses PostgreSQL as the databa
se management system. \line \up0 \expndtw-10\charscalex93 Scripts are implemen
ted using the XSP \up0 \expndtw-10\charscalex95 (extensible server pages) \
par\pard\qj \li2268\ri2026\sb0\sl-433\slmult0 \up0 \expndtw-10\charscalex91 lang
uage, which generates XML documents dynamically. The XML \line \up0 \expn
dtw-10\charscalex95 documents are transformed to HTML on the server side, to avo
id any \line \up0 \expndtw-10\charscalex91 problems of incompatibility among dif
ferent types and versions of Web \line \up0 \expndtw-10\charscalex92 browsers. \
par\pard\qj \li2268\ri2026\sb0\sl-420\slmult0 \up0 \expndtw-10\charscalex93 The
XSP scripts run on Cocoon version 1.7, which runs on the servlet \up0 \expndtw-1
0\charscalex89 container Tomcat, version 3.2. \par\pard\ql \li2268\sb0\sl-253\sl
mult0 \par\pard\ql\li2268\sb0\sl-253\slmult0 \par\pard\ql\li2268\sb0\sl-253\slmu
lt0 \par\pard\ql\li2268\sb225\sl-253\slmult0 \up0 \expndtw-6\charscalex100 THE W
WW INTERFACE \par\pard\qj \li2268\ri2026\sb41\sl-430\slmult0 \up0 \expndtw-8\cha
rscalex100 The TissueDB WWW interface provides two browsing systems with \up0 \e
xpndtw-9\charscalex91 regard to tissues; one is a hierarchy browser and the othe
r is a detailed \up0 \expndtw-10\charscalex89 information browser. \par\pard\qj
\li2268\ri2026\sb0\sl-430\slmult0 \up0 \expndtw-9\charscalex88 The TissueDB
hierarchy browser visualizes the anatomical and \line \up0 \expndtw-9\
charscalex90 histological relation between objects of the adult human body (Figu
re 1). \line \up0 \expndtw-10\charscalex93 The anatomical hierarchy starts w
ith the object \up0 \expndtw-10\charscalex87 body \up0 \expndtw-10\charscalex9
2 , and the \par\pard\ql \li2268\sb127\sl-253\slmult0\tx5769\tx6417 \up0 \expn
dtw-10\charscalex91 histological hierarchy starts with \tab \up0 \expndtw-10\cha
rscalex97 tissue \tab \up0 \expndtw-10\charscalex88 . Clicking on a rightward ar
row \par\pard\qj \li2268\ri2026\sb21\sl-430\slmult0 \up0 \expndtw-10\charscalex9
3 icon displays the lower hierarchy, and clicking on an upward arrow \line \up0
\expndtw-10\charscalex92 displays the upper hierarchy. A round icon preceding th
e name of an \line \up0 \expndtw-7\charscalex100 object indicates a \up0 \expndt
w-10\charscalex94 categorical\u8217?relation, and a square icon indicates a \par
\pard\ql \li2313\sb157\sl-253\slmult0\tx3115 \up0 \expndtw-10\charscalex93 part
of \tab \up0 \expndtw-10\charscalex90 (structural) relation. \par\pard\ql \li226
8\sb167\sl-253\slmult0\tx4567 \up0 \expndtw-10\charscalex94 Clicking on an objec
t \tab \up0 \expndtw-10\charscalex93 s name displays detailed information about
the \par\pard\ql \li2268\sb167\sl-253\slmult0 \up0 \expndtw-9\charscalex92 objec
t. The detailed information includes the TissueID, the name of the
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}}
{\shp {\*\shpinst\shpleft7813\shptop11926\shpright9273\shpbottom12324\shpfhdr0\s
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{\sp{\sn shapeType}{\sv 202}}{\sp{\sn fFlipH}{\sv 0}}{\sp{\sn fFlipV}{\sv 0}}{\s
p{\sn fRecolorFillAsPicture}{\sv 0}}{\sp{\sn fUseShapeAnchor}{\sv 0}}{\sp{\sn fL
ine}{\sv 0}}{\sp{\sn fFilled}{\sv 0}}{\sp{\sn fLayoutInCell}{\sv 1}}{\sp{\sn fBe
hindDocument}{\sv 1}}{\shptxt\pard\plain \qj\sl162 \li0\ri0 \expndtw-3\charscale
x100\ul0\nosupersub\cf3\f4\fs22 \u8216?{\par}}}}
{\shp {\*\shpinst\shpleft2128\shptop14062\shpright3588\shpbottom14460\shpfhdr0\s
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{\sp{\sn shapeType}{\sv 202}}{\sp{\sn fFlipH}{\sv 0}}{\sp{\sn fFlipV}{\sv 0}}{\s
p{\sn fRecolorFillAsPicture}{\sv 0}}{\sp{\sn fUseShapeAnchor}{\sv 0}}{\sp{\sn fL
ine}{\sv 0}}{\sp{\sn fFilled}{\sv 0}}{\sp{\sn fLayoutInCell}{\sv 1}}{\sp{\sn fBe
hindDocument}{\sv 1}}{\shptxt\pard\plain \qj\sl162 \li0\ri0 \expndtw-3\charscale
x100\ul0\nosupersub\cf3\f4\fs22 \u8216?{\par}}}}
\par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg6
}{\bkmkend Pg6}\par\pard\qj \li2268\sb0\sl-430\slmult0 \par\pard\qj\li2268\ri202
6\sb394\sl-430\slmult0 \up0 \expndtw-9\charscalex92 \ul0\nosupersub\cf3\f4\fs22
tissue, synonyms, and relation to other tissues. In addition, clicking on \line
\up0 \expndtw0\charscalex105 the \up0 \expndtw-10\charscalex84 cell line \up0 \e
xpndtw-10\charscalex89 icon on the page of detailed information brings up a list
of \line \up0 \expndtw-10\charscalex90 cell line names that originate from the
tissue, and clicking on the \par\pard\qj \li2268\ri2026\sb0\sl-440\slmult0\fi45
\up0 \expndtw-8\charscalex100 UniLib\u8217?icon displays a list of UniGene libra
ries that relate to the \line \up0 \expndtw-8\charscalex100 tissue. \par\pard\qj
\li2268\ri2026\sb0\sl-430\slmult0 \up0 \expndtw-9\charscalex91 A tissue name ca
n be searched using the search interface; a tissue object \line \up0 \expndtw-10
\charscalex94 can be searched using either a tissue name or TissueID. Tissue nam
es \line \up0 \expndtw-10\charscalex96 consist of names and synonyms. In additio
n, expression data can be \line \up0 \expndtw-10\charscalex92 searched using the
name of a gene. Search targets are shown as options \line \up0 \expndtw-9\chars
calex89 to be checked under the query form. A wild card (*) search is available.
\par\pard\ql \li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0
\par\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0 \p
ar\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0 \par
\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb131\sl-241\slmult0 \up0
\expndtw-5\charscalex100 \ul0\nosupersub\cf1\f2\fs21 ACKNOWLEDGEMENT \par\pard\
qj \li2268\ri2034\sb45\sl-428\slmult0 \up0 \expndtw-9\charscalex94 We would like
to thank Dr. T. Kaminuma (National Institutes of Health \up0 \expndtw-8\charsca
lex91 Science, Tokyo) for his initial contribution. Thanks also go to IMS Lab. I
nc. \up0 \expndtw-9\charscalex95 for their programming support and database main
tenance. This work is \up0 \expndtw-9\charscalex92 supported in part by New Ener
gy and Industrial Technology Development \up0 \expndtw-8\charscalex93 Organizati
on (NEDO) and Ministry of Education, Culture, Sports, Science \up0 \expndtw-9\ch
arscalex93 and Technology (MEXT). \par\pard\ql \li2268\sb0\sl-241\slmult0 \par\p
ard\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0 \par\par
d\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\
ql\li2268\sb222\sl-241\slmult0 \up0 \expndtw-5\charscalex100 REFERENCES \par\par
d\qj \li2268\ri2034\sb21\sl-433\slmult0 \up0 \expndtw-8\charscalex95 1. Wheele
r,D.L., Church,D.M., Lash,A.E., Leipe,D.D., Madden,T.L., \line \up0 \exp
ndtw-8\charscalex93 Pontius,J.U., Schuler,G.D., Schriml,L.M., Tatusova,T.A.,
Wagner,L. and \line \up0 \expndtw-9\charscalex93 Rapp,B.A. \up0 \expndtw-9\cha
rscalex90 (2002) Database resources of the National Center for \li
ne \up0 \expndtw-9\charscalex87 Biotechnology Information: 2002 update. Nucleic
Acids Res., 30, 13-16 \par\pard\qj \li2268\ri2034\sb410\sl-430\slmult0\tx2764 \u
p0 \expndtw-9\charscalex89 2. \tab \up0 \expndtw-9\charscalex93 Sherlock,G.,
Hernandez-Boussard,T., Kasarskis,A., Binkley,G., \line \up0 \expndtw-7\cha
rscalex100 Matese,J.C., Dwight,S.S., Kaloper,M., Weng,S., Jin,H., Ball
,C.A., \line \up0 \expndtw-8\charscalex93 Eisen,M.B., Spellman,P.T., Brown,P.O.,
Botstein,D. and Cherry,J.M. (2001)
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{\sp{\sn shapeType}{\sv 0}}{\sp{\sn fFlipH}{\sv 0}}{\sp{\sn fFlipV}{\sv 0}}{\sp{
\sn geoRight}{\sv 11900}}{\sp{\sn geoBottom}{\sv 16840}}
{\sp{\sn pVerticies}{\sv 8;5;(0,16840);(11900,16840);(11900,0);(0,4);(0,16840)}}
{\sp{\sn pSegmentInfo}{\sv 2;11;16384;45824;1;45824;1;45824;1;45824;1;45824;3276
8}}
{\sp{\sn fFillOK}{\sv 1}}{\sp{\sn fFilled}{\sv 1}}{\sp{\sn fillColor}{\sv 167772
15}}{\sp{\sn fLine}{\sv 0}}{\sp{\sn lineType}{\sv 0}}{\sp{\sn fArrowheadsOK}{\sv
1}}{\sp{\sn fBehindDocument}{\sv 1}}{\sp{\sn lineColor}{\sv 0}}
}}
{\shp {\*\shpinst\shpleft2128\shptop2521\shpright3588\shpbottom2919\shpfhdr0\shp
bxpage\shpbypage\shpwr3\shpwrk0\shpfblwtxt1\shpz10001\shplid10001
{\sp{\sn shapeType}{\sv 202}}{\sp{\sn fFlipH}{\sv 0}}{\sp{\sn fFlipV}{\sv 0}}{\s
p{\sn fRecolorFillAsPicture}{\sv 0}}{\sp{\sn fUseShapeAnchor}{\sv 0}}{\sp{\sn fL
ine}{\sv 0}}{\sp{\sn fFilled}{\sv 0}}{\sp{\sn fLayoutInCell}{\sv 1}}{\sp{\sn fBe
hindDocument}{\sv 1}}{\shptxt\pard\plain \qj\sl162 \li0\ri0 \expndtw-3\charscale
x100\ul0\nosupersub\cf3\f4\fs22 \u8216?{\par}}}}
\par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg7
}{\bkmkend Pg7}\par\pard\ql \li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\s
l-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-
241\slmult0 \par\pard\ql\li2268\sb16\sl-241\slmult0 \up0 \expndtw-9\charscalex88
\ul0\nosupersub\cf1\f2\fs21 The Stanford Microarray Database. Nucleic Acids Res
., 29, 152-155 \par\pard\qj \li2268\sb0\sl-426\slmult0 \par\pard\qj\li2268\ri203
4\sb41\sl-426\slmult0 \up0 \expndtw-8\charscalex93 3. Kawamoto,S., Yoshii,J.,
Mizuno,K., Ito,K., Miyamoto,Y., Ohnishi,T., \line \up0 \expndtw-8\charscalex
92 Matoba,R., Hori,N., Matsumoto,Y., Okumura,T., Nakao,Y., Yoshii,H.,
\line \up0 \expndtw-8\charscalex95 Arimoto,J., Ohashi,H., Nakanishi,H., Ohno,I.,
Hashimoto,J., Shimizu,K., \line \up0 \expndtw-8\charscalex91 Maeda,K., Kuriyam
a,H., Nishida,K., Shimizu-Matsumoto,A., Adachi,W., \line \up0 \expndtw-8\char
scalex93 Ito,R., Kawasaki,S. and Chae,K.S. (2000) BodyMap: a collection of 3' ES
Ts \line \up0 \expndtw-8\charscalex100 for analysis of human gene expression inf
ormation. Genome Res., 10, \line \up0 \expndtw-9\charscalex77 1817-1827 \par\par
d\li2268\sb0\sl-241\slmult0\par\pard\li2268\sb0\sl-241\slmult0\par\pard\li2268\s
b112\sl-241\slmult0\fi0\tx5851 \up0 \expndtw-9\charscalex90 4. Bowden,D.M. and
Martin,R.F.\tab \up0 \expndtw-9\charscalex90 (1995) Neuronames brain hierar
chy.\par\pard\li2268\sb186\sl-241\slmult0\fi0 \up0 \expndtw-9\charscalex90 Neuro
image, 2, 63-83.\par\pard\qj \li2268\sb0\sl-426\slmult0 \par\pard\qj\li2268\ri20
34\sb27\sl-426\slmult0\tx2747 \up0 \expndtw-9\charscalex89 5. \tab \up0 \expndtw
-9\charscalex93 Bard,J., Kaufman,M.H., Dubreuil,C., Brune,R.M., Burg
er,A., \up0 \expndtw-8\charscalex92 Baldock,R.A. and Davidson,D.R. (1998) An int
ernet-accessible database of \up0 \expndtw-9\charscalex91 mouse developmental an
atomy based on a systematic nomenclature. Mech. \up0 \expndtw-9\charscalex83 Dev
., 74, 111-120. \par\pard\qj \li2268\sb0\sl-420\slmult0 \par\pard\qj\li2268\ri20
34\sb19\sl-420\slmult0 \up0 \expndtw-9\charscalex97 6. Bard,J. and Winter,R. (20
01) Ontologies of developmental anatomy: \up0 \expndtw-9\charscalex88 Their curr
ent and future roles. Briefings. Bioinformatics, 2, 289-299. \par\pard\qj \li226
8\sb0\sl-426\slmult0 \par\pard\qj\li2268\ri2034\sb10\sl-426\slmult0 \up0 \expndt
w-8\charscalex92 7. Wingender,E., Chen,X., Fricke,E., Geffers,R., Hehl
,R., Liebich,I., \up0 \expndtw-8\charscalex93 Krull,M., Matys,V., Michael,H.
, Ohnhauser,R., Pruss,M., Schacherer,F., \up0 \expndtw-9\charscalex92 Thiele,
S. and Urbach,S. (2001) The TRANSFAC system on gene expression \up0 \expndtw-9\c
harscalex86 regulation. Nucleic Acids Res., 29, 281-283
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15}}{\sp{\sn fLine}{\sv 0}}{\sp{\sn lineType}{\sv 0}}{\sp{\sn fArrowheadsOK}{\sv
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}}\par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart P
g8}{\bkmkend Pg8}\par\pard\ql \li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0
\sl-241\slmult0 \par\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb0\s
l-241\slmult0 \par\pard\ql\li2268\sb16\sl-241\slmult0 \up0 \expndtw-9\charscalex
100 \ul0\nosupersub\cf1\f2\fs21 Figure Legends \par\pard\qj \li2268\sb0\sl-420\s
lmult0 \par\pard\qj\li2268\ri2034\sb52\sl-420\slmult0 \up0 \expndtw-9\charscalex
100 Figure 1. The top level data hierarchy of anatomy (left) and histology \line
\up0 \expndtw-9\charscalex93 (right). \par\pard\ql \li2268\sb0\sl-241\slmult0 \
par\pard\ql\li2268\sb0\sl-241\slmult0 \par\pard\ql\li2268\sb106\sl-241\slmult0 \
up0 \expndtw-9\charscalex90 Figure 2. An example of search result for molecules.

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