there are currently 1170 biological databases in the world ( 1 ) that are being utilized for various researches and developments .
it is now possible for biologists to try to make discoveries by combining and linking data of different types obtained from multiple databases .
for example , by combining protein sequences and protein structure data that are stored separately in major databases , biologists can study the basic rules of protein 3d structure such as how amino - acid sequences organize themselves into specific and stable 3d structures . in this way , linking specific data stored in multiple databases will lead to the organization of biological knowledge and will provide useful resources for novel researches . finding corresponding data in different databases and setting hyperlinks among them is an effective way of integrating information that are stored in independently operated databases in different organizations .
the maintenance of the hyperlinks among many databases , however , requires a huge cost , because the number of pairs of databases is generally very large .
for example , possible ways of hyperlinks among n related databases will be ( n  1)n , if we consider the directions of hyperlinks .
suppose if one of the n databases is updated , 2(n  1 ) ways of hyperlinks need to be updated .
if each of n databases is periodically updated in every 3 months , at most 8(n  1)n ways of hyperlinks need to be updated in a year , which will be a laborious work .
, we developed a web server for automatically managing and updating hyperlinks that can connect molecular information in multiple databases about human genes and proteins .
furthermore , we developed a web server for converting data ids from one type to another .
the reason for it is that , for database developers , these systems can realize automated , work - saving and efficient management of databases , and can reduce the large cost of maintaining biological databases .
also , for biologists , especially those who are unfamiliar with the data ids of major biological databases , our newly developed web servers will be of help in carrying out efficient analyses of  big data that are being produced massively in laboratories ( 2 ) .
hms is a tool for automatically updating and maintaining hyperlinks between databases in the field of life science .
the hms automatically downloads the lists of data ids for human genes and proteins and their relations from major biological databases everyday , and produces large corresponding tables of all data ids of these databases ( tables 1 and 2 ) . then , using the corresponding tables of data ids , the hms shows the most up - to - date urls for data in a database that are corresponding to a user - specified i d of another database .
the url is easily obtained by running a cgi - program of the hms . 

table 1.databases and viewers handled by the hmsdatabase nameviewer nameformath - invdb ( 3,4)transcript viewtranscriptviewlocus viewlocusviewg - integragintegrappi viewppiinsd ( ddbj / embl/ genbank ) ( 57)ncbi nucleotidenucleotidencbi entrez gene ( 8)entrez geneentrezgenegenome medicine database of japan ( gemdbj ) ( 9)gemdbjgemdbjhugo gene nomenclature committee ( hgnc ) database ( 10)hgnchugomutationview ( 11)mutationviewmutationviewh - gold ( 12)h - goldhgoldpdb ( 13)pdbpdbuniprot ( 14)uniprotkbuniprotensembl ( 15)gene summaryensgtranscript summaryenstglycogene database ( ggdb ) ( 16)ggdbggdbfrnadb ( 17)frnadbfrnadbhuman gene and protein database ( hgpd ) ( 18)hgpdhgpdparameters of database names used in the hms cgi - program , ics and web service . 
 table 2.data ids used in the hmssource databasedata idformatcounth - invdbh - inv transcript i d ( hit)hit_id219 765h - inv cluster i d ( hix)hix_id43 159h - inv protein i d ( hip)hip_id133 629insdaccession numberacc_id222 136ncbiomim idomim_id16 253refseq idref_seq48 671entrez gene idgene_id40 235gemdbjdbsnp rs#jsnp_id76 024hugohugo gene symbolgene_symbol26 421h - goldh - gold marker namems_id494pdbpdb
idpdb_id50 958uniprotuniprot iduniprot_id84 422ensemblensembl transcript idenst63 280ensembl gene idensg37 435frnadbfrnadb idfr_id41 501hgpdcdna clone idpdb_id21 340flj cdna clonesflj_id21 340parameters of i d types used in the hms cgi - program , ics and web service.number of data as of 23 january 2009 .
databases and viewers handled by the hms parameters of database names used in the hms cgi - program , ics and web service .
data ids used in the hms parameters of i d types used in the hms cgi - program , ics and web service .
suppose that the manager of database a wishes to create hyperlinks from database a to database b. usually in this case , the manager uses data ids of database b in the urls of hyperlinks .
however , if the manager uses the hms , he can use data ids of database a to create hyperlinks to database b. this is very useful because we can easily create hyperlinks without knowing data ids of target databases .
currently , the hms collects 17 types of data ids for human genes and proteins ( table 2 ) . among the 17 types of data ids , we defined accession numbers of international nucleotide sequence database ( insd ; ddbj / embl / genbank ) , hugo gene symbols and uniprot ids as 
we collect corresponding tables between a common i d and an other i d from each of source databases ( figure 1 ) .
we also obtain a corresponding table between accession numbers and hugo gene symbols from ncbi and a corresponding table between accession numbers and uniprot ids from uniprot . using these tables
, we create a large corresponding table that shows the relationships among 17 types of data ids .
the common ids define the route of i d conversion ( as shown in figure 1 ) .
for example , when converting hix of h - invdb into pdb ids , we first convert hix into uniprot ids and then convert it into pdb ids . 

for all these ids , the hms and the i d converter system are capable of setting hyperlinks and i d conversion .  common ids that were used as key ids in i d conversion are shown in red , blue or green .
for example , when converting hugo gene symbols into pdb ids , the system first converts hugo gene symbols into accession numbers according to a corresponding table obtained from ncbi , and then converts accession numbers into uniprot ids according to a corresponding table obtained from uniprot , and then converts uniprot ids into pdb ids according to a corresponding table obtained from pdbj . live lists of data ids and their corresponding tables are collected daily from each of these databases .
for all these ids , the hms and the i d converter system are capable of setting hyperlinks and i d conversion .
 common ids that were used as key ids in i d conversion are shown in red , blue or green .
for example , when converting hugo gene symbols into pdb ids , the system first converts hugo gene symbols into accession numbers according to a corresponding table obtained from ncbi , and then converts accession numbers into uniprot ids according to a corresponding table obtained from uniprot , and then converts uniprot ids into pdb ids according to a corresponding table obtained from pdbj .
live lists of data ids and their corresponding tables are collected daily from each of these databases .
the hms directly opens a web page of the target database if there is only one data i d corresponding to the source i d .
however , in converting data ids , an i d does not always correspond to one i d of another type .
if there are more than one ids corresponding to the source i d , the hms shows the list of all corresponding data ids with appropriate hyperlinks , from which users can choose and open the data of interest . in order to create hyperlinks using the hms cgi - program , use the following url as a target url .
http://biodb.jp/hfs.cgi?id = [ id]&type = [ i d type]&db = [ database name ] here , [ i d ] is a data i d of the database from which hyperlink is set , [ i d type ] is a kind of the data i d and [ database name ] is the name of database to which hyperlink is set .
details of parameter settings are shown in tables 1 and 2 and also in the online help pages of the hms .
for example , using bc053 657 , an accession number of insd , you can create a hyperlink toward the corresponding 
< a href = " http://biodb.jp/hfs.cgi?id=bc053657&type=acc_id&db=transcriptview">bc053 657</a > this cgi - program is freely available to all users in the world . for database managers , if their databases have any one of those data ids shown in table 2 , it is possible to create hyperlinks from the database to all the databases shown in table 1 through the hms .
because the hyperlinks of the hms are automatically updated everyday , the connection to the latest data is always guaranteed .
the hms cgi - program is supposed to be used for hyperlinking among databases . however , there are situations that we want to query with a small number of data ids .
we thus developed a web server of the same function as the cgi - program ( figure 2 ) . here
, by utilizing the same corresponding tables of data ids as those of the cgi version , users can open web pages of a database corresponding to a specified data i d of another database .
the usage of the hms web server is quite simple and requires no complicated explanations .
for example , if you enter an accession number of insd in the  source id and push the 
, users can enter multiple data ids delimited by a space , tab or comma . in this case
, the result page shows a list of multiple urls with hyperlinks corresponding to each data . 

input source ids in the textbox , and select the type of ids . then , select database to open , and push the  search button .
then , the hms searches for ids that correspond to the source ids and opens pages of destination databases .
if there are two or more corresponding data , the hms shows the list of ids with hyperlinks .
this figure shows an example of opening locus view of h - invdb with an accession number bc053657 .
input source ids in the textbox , and select the type of ids . then , select database to open , and push the  search button . then , the hms searches for ids that correspond to the source ids and opens pages of destination databases .
if there are two or more corresponding data , the hms shows the list of ids with hyperlinks .
this figure shows an example of opening locus view of h - invdb with an accession number bc053657 .
ics is a tool for converting data ids used in a database into other , corresponding ids used in other databases ( figure 3 ) .
multiple ids can be converted at a time , if users enter multiple data ids delimited by a space , tab or comma .
when a data i d can be converted into multiple corresponding ids , the ics shows all the corresponding ids .
users can also specify a file on their client pc , and convert a list of data ids in it .
furthermore , the ics is accessible by computer programs using the web service , as will be described later . 

then , select the type of data i d to convert , and push the  search button .
then , the system searches for ids that correspond to source ids , and shows the list of them .
this figure shows an example of converting two accession numbers , bc053657 and z34290 , into hugo gene symbols .
then , select the type of data i d to convert , and push the  search button .
then , the system searches for ids that correspond to source ids , and shows the list of them
this figure shows an example of converting two accession numbers , bc053657 and z34290 , into hugo gene symbols . for those who wish to analyze massive data by computers ,
the hms and ics accept queries through the web service , which makes it possible to call functions of these systems through computer programs .
the details of commands for the web service will be shown if you click the 
web service button on the upper right corner of the web pages ( figures 2 and 3 ) . on these pages
, there are some sample programs for the web service . furthermore , we prepared statistics pages of the hsm and ics .
if you click the  update info button on the upper right corner of the top pages ( figures 2 and 3 ) , the number of data ids downloaded from each database everyday will be shown .
release info button , the number of pages of each database that are hyperlinked through various data ids will be shown .
finally , there are help pages that explain how to use the hms and ics .
hms is a tool for automatically updating and maintaining hyperlinks between databases in the field of life science .
the hms automatically downloads the lists of data ids for human genes and proteins and their relations from major biological databases everyday , and produces large corresponding tables of all data ids of these databases ( tables 1 and 2 ) . then , using the corresponding tables of data ids , the hms shows the most up - to - date urls for data in a database that are corresponding to a user - specified i d of another database .
the url is easily obtained by running a cgi - program of the hms . 

table 1.databases and viewers handled by the hmsdatabase nameviewer nameformath - invdb ( 3,4)transcript viewtranscriptviewlocus viewlocusviewg - integragintegrappi viewppiinsd ( ddbj / embl/ genbank ) ( 57)ncbi nucleotidenucleotidencbi entrez gene ( 8)entrez geneentrezgenegenome medicine database of japan ( gemdbj ) ( 9)gemdbjgemdbjhugo gene nomenclature committee ( hgnc ) database ( 10)hgnchugomutationview ( 11)mutationviewmutationviewh - gold ( 12)h - goldhgoldpdb ( 13)pdbpdbuniprot ( 14)uniprotkbuniprotensembl ( 15)gene summaryensgtranscript summaryenstglycogene database ( ggdb ) ( 16)ggdbggdbfrnadb ( 17)frnadbfrnadbhuman gene and protein database ( hgpd ) ( 18)hgpdhgpdparameters of database names used in the hms cgi - program , ics and web service . 
 table 2.data ids used in the hmssource databasedata idformatcounth - invdbh - inv transcript i d ( hit)hit_id219 765h - inv cluster i d ( hix)hix_id43 159h - inv protein i d ( hip)hip_id133 629insdaccession numberacc_id222 136ncbiomim idomim_id16 253refseq idref_seq48 671entrez gene idgene_id40 235gemdbjdbsnp rs#jsnp_id76 024hugohugo gene symbolgene_symbol26 421h - goldh - gold marker namems_id494pdbpdb
idpdb_id50 958uniprotuniprot iduniprot_id84 422ensemblensembl transcript idenst63 280ensembl gene idensg37 435frnadbfrnadb idfr_id41 501hgpdcdna clone idpdb_id21 340flj cdna clonesflj_id21 340parameters of i d types used in the hms cgi - program , ics and web service.number of data as of 23 january 2009 .
databases and viewers handled by the hms parameters of database names used in the hms cgi - program , ics and web service .
data ids used in the hms parameters of i d types used in the hms cgi - program , ics and web service .
suppose that the manager of database a wishes to create hyperlinks from database a to database b. usually in this case , the manager uses data ids of database b in the urls of hyperlinks .
however , if the manager uses the hms , he can use data ids of database a to create hyperlinks to database b. this is very useful because we can easily create hyperlinks without knowing data ids of target databases .
currently , the hms collects 17 types of data ids for human genes and proteins ( table 2 ) . among the 17 types of data ids , we defined accession numbers of international nucleotide sequence database ( insd ; ddbj / embl / genbank ) , hugo gene symbols and uniprot ids as 
we collect corresponding tables between a common i d and an other i d from each of source databases ( figure 1 ) .
we also obtain a corresponding table between accession numbers and hugo gene symbols from ncbi and a corresponding table between accession numbers and uniprot ids from uniprot . using these tables
, we create a large corresponding table that shows the relationships among 17 types of data ids .
the common ids define the route of i d conversion ( as shown in figure 1 ) .
for example , when converting hix of h - invdb into pdb ids , we first convert hix into uniprot ids and then convert it into pdb ids . 

for all these ids , the hms and the i d converter system are capable of setting hyperlinks and i d conversion .  common ids that were used as key ids in i d conversion are shown in red , blue or green .
for example , when converting hugo gene symbols into pdb ids , the system first converts hugo gene symbols into accession numbers according to a corresponding table obtained from ncbi , and then converts accession numbers into uniprot ids according to a corresponding table obtained from uniprot , and then converts uniprot ids into pdb ids according to a corresponding table obtained from pdbj . live lists of data ids and their corresponding tables are collected daily from each of these databases .
for all these ids , the hms and the i d converter system are capable of setting hyperlinks and i d conversion .
 common ids that were used as key ids in i d conversion are shown in red , blue or green .
for example , when converting hugo gene symbols into pdb ids , the system first converts hugo gene symbols into accession numbers according to a corresponding table obtained from ncbi , and then converts accession numbers into uniprot ids according to a corresponding table obtained from uniprot , and then converts uniprot ids into pdb ids according to a corresponding table obtained from pdbj .
live lists of data ids and their corresponding tables are collected daily from each of these databases .
the hms directly opens a web page of the target database if there is only one data i d corresponding to the source i d .
however , in converting data ids , an i d does not always correspond to one i d of another type .
if there are more than one ids corresponding to the source i d , the hms shows the list of all corresponding data ids with appropriate hyperlinks , from which users can choose and open the data of interest . in order to create hyperlinks using the hms cgi - program , use the following url as a target url . http://biodb.jp/hfs.cgi?id = [ id]&type = [ i d type]&db = [ database name ] here , [ i d ] is a data i d of the database from which hyperlink is set , [ i d type ] is a kind of the data i d and [ database name ] is the name of database to which hyperlink is set .
details of parameter settings are shown in tables 1 and 2 and also in the online help pages of the hms .
for example , using bc053 657 , an accession number of insd , you can create a hyperlink toward the corresponding 
< a href = " http://biodb.jp/hfs.cgi?id=bc053657&type=acc_id&db=transcriptview">bc053 657</a > this cgi - program is freely available to all users in the world . for database managers , if their databases have any one of those data ids shown in table 2 , it is possible to create hyperlinks from the database to all the databases shown in table 1 through the hms . because the hyperlinks of the hms are automatically updated everyday , the connection to the latest data is always guaranteed .
the hms cgi - program is supposed to be used for hyperlinking among databases . however , there are situations that we want to query with a small number of data ids .
we thus developed a web server of the same function as the cgi - program ( figure 2 ) . here
, by utilizing the same corresponding tables of data ids as those of the cgi version , users can open web pages of a database corresponding to a specified data i d of another database .
the usage of the hms web server is quite simple and requires no complicated explanations .
for example , if you enter an accession number of insd in the  source id and push the  search button , you can open the  locus view of h - invdb . in the textbox , users can enter multiple data ids delimited by a space , tab or comma . in this case , the result page shows a list of multiple urls with hyperlinks corresponding to each data . 

input source ids in the textbox , and select the type of ids . then , select database to open , and push the  search button .
then , the hms searches for ids that correspond to the source ids and opens pages of destination databases .
if there are two or more corresponding data , the hms shows the list of ids with hyperlinks .
this figure shows an example of opening locus view of h - invdb with an accession number bc053657 .
input source ids in the textbox , and select the type of ids . then , select database to open , and push the  search button .
then , the hms searches for ids that correspond to the source ids and opens pages of destination databases .
if there are two or more corresponding data , the hms shows the list of ids with hyperlinks .
this figure shows an example of opening locus view of h - invdb with an accession number bc053657 .
ics is a tool for converting data ids used in a database into other , corresponding ids used in other databases ( figure 3 ) .
multiple ids can be converted at a time , if users enter multiple data ids delimited by a space , tab or comma .
when a data i d can be converted into multiple corresponding ids , the ics shows all the corresponding ids .
users can also specify a file on their client pc , and convert a list of data ids in it .
furthermore , the ics is accessible by computer programs using the web service , as will be described later . 

then , select the type of data i d to convert , and push the  search button .
then , the system searches for ids that correspond to source ids , and shows the list of them
this figure shows an example of converting two accession numbers , bc053657 and z34290 , into hugo gene symbols .
then , select the type of data i d to convert , and push the  search button .
then , the system searches for ids that correspond to source ids , and shows the list of them
this figure shows an example of converting two accession numbers , bc053657 and z34290 , into hugo gene symbols .
for those who wish to analyze massive data by computers , the hms and ics accept queries through the web service , which makes it possible to call functions of these systems through computer programs .
the details of commands for the web service will be shown if you click the  web service button on the upper right corner of the web pages ( figures 2 and 3 ) . on these pages , there are some sample programs for the web service .
if you click the  update info button on the upper right corner of the top pages ( figures 2 and 3 ) , the number of data ids downloaded from each database everyday will be shown .
if you click the  release info button , the number of pages of each database that are hyperlinked through various data ids will be shown .
finally , there are help pages that explain how to use the hms and ics .
as has been stated earlier , there are currently 1170 databases in the field of life sciences that are listed in the online molecular biology database collection of nucleic acids research ( 1 ) .
because biologists usually wish to combine a certain type of data with another , integration of these various and huge databases will be of great significance . in principle , there are two possible ways of integrating databases .
one is to collect all the databases at one place and merge them , while the other is to combine the databases virtually by hyperlinking corresponding data among them .
the former method requires an enormous amount of disk space of computers and a large number of people to maintain and update the databases . in other words ,
in fact , there was an attempt to construct a huge integrated database of many biological data by the former method , which failed in a few years probably due to the high running cost .
the latter method , on the other hand , can be realized relatively easily if we adopt the automated hyperlinking that we introduced in this article .
the hms will be a fundamental platform to virtually integrate databases that are operated independently by different organizations .
furthermore , the hms will make it possible for us to construct integrated databases in a sustainable way .
the ics is also a quite useful tool . because major databases such as insd and uniprot update their  live lists of data ids on a daily basis , the role of ics to provide users with the up - to - date information of i d
the usage of the ics is very simple , and anyone can make full use of it easily .
for example , even when one has a list of hugo gene symbols for 100 genes , he / she can easily find corresponding data in h - invdb , uniprot , pdb and other databases through the ics .
the most important feature of the ics is that i d conversion can be done between two types of data ids that are not directly related .
the ics can convert from and to all data ids shown in figure 1 , including those that are not directly connected .
for example , the ics can directly convert accession numbers of isnd into pdb ids .
we thus think that the ics will be a useful web server for many researchers .
we plan to add more and more databases into the hms and ics in the future .
it is easy to add new databases as destination of hms hyperlinks if the database uses either accession numbers of insd , uniprot ids or pdb ids .
furthermore , we have been dealing with databases about human molecular data , but we plan to extend the hms to molecular data of other species in near future . the ics will be also extended to incorporate other ids that are frequently used by biologists .
for example , we will incorporate ids of literature databases , which will enable combining biological knowledge in literature with molecular data .
the hms and ics will be of considerable use as an automated tool for database managers and as a new indispensable tool for biologists
. we may be able to extend these systems to incorporate keyword searches that are frequently used in many databases . by indexing general and technical terms by assigning them some ids
integrated database project of the ministry of economy , trade and industry of japan ; research grant for promoting science and technology from japan science and technology agency .
 hyperlink management system ( hms ) is a system for automatically updating and maintaining hyperlinks among major public databases in the field of life science . 
 we daily create corresponding tables of data ids of major databases for human genes and proteins , and provide a cgi - program that returns correct and up - to - date urls for showing data of various databases that correspond to user - specified ids . 
 the hms can deal with various ids : accession numbers of international nucleotide sequence databases , hugo gene symbols and ids of uniprot , pdb , h - invdb and others , and it can return urls of various databases : h - invdb , hugo gene nomenclature committee database , ncbi entrez gene , uniprot , pdb and others . 
 for example , 23 297 pages of locus view of h - invdb are reachable by using hugo gene symbols through the hms . 
 not only the cgi - program , the hms provides a web page for finding and opening urls of these databases . 
 although hyperlinking is an effective way of relating biological data among different databases , updating hyperlinks has been a laborious work . 
 the hms fully automates the job , enabling maintenance - free hyperlinks . 
 we also developed the i d converter system ( ics ) for simply converting data ids by using corresponding tables in the hms . 
 the hms and ics are freely available at http://biodb.jp/. 
INTRODUCTION
WEB SERVER FEATURES
Usage of the Hyperlink Management System (HMS) CGI-program
Usage of the HMS Web Server
Usage of the ID Converter System (ICS)
Web service and other functions
DISCUSSION
FUNDING