owrd thwy ingineeringX
e xew htse of qeneti nd
woleulr thwys
winoru unehis
snstitute for ghemil eserhD uyoto niversity
ing of genes nd moleules is prom qenome eE sequening pro jets hve een
lso rpidly expnding owing to ompleted for udding yest @IP
quenes to puntions
the dvnement of exp erimenE wpA nd for severl teri inE
tl tehnologies in the rod luding ynoteri @QFT wpA
he rumn qenome ro jet
res of moleulr nd ellulr whih ws rried out y the
ws initited in the lte IWVHs
iologyF sn order to mke full uzus hxe eserh snstitute
s nturl onsequene of
use of the informtion otined in tpnF
the tehnology developments in
y genome pro jetsD it is essenE
por the rst time in humn moleulr iology nd with the
til tht suh funtionl dt
history we re eginning to hve expettion of new iomedil
re prop erly omputerized in
the dt t hnd whih leds toE pplitionsF he pro jet will
dtses nd informtis tehE
wrd si understnding of unover the omplete hxe seE
nologies re developed for funE
quene of the humn genome the fundmentl prolems in life
tionl preditionF
onsisting of Q illion se pirs sienes inluding the origin nd
nd IHH thousnd genesF sn evolution of life nd the onE
prom qene qtlogs
IWUUD smll virus genomeD eption nd developmentofn
0xIURD onsisting of just SDHHH individulF he dt will lso
to thwys
se pirs nd II genes ws deE stimulte prtil pplitions
he funtionl dt tht relte termined y the emerging tehE in medilD phrmeutilD nd
to sequene informtion re urE nology of hxe sequene deterE griulturl sienesF roweverD
rently stored s nnottions to mintionF efter two dedes somewht ontrry to puli noE
sequene dtD for exmpleD in of tehnology developments the tionD the sequene dt otined
the soElled fetures tlesD in y genome pro jets do not y rst omplete genome of
the sequene dtses of hxes themselves provide diret nE freeEliving iologil orgnismD
nd proteinsF roweverD these swers to suh fundmentl proE remophilus inuenzeD ws deE
silly represent the sequeneE lems or prtil pplitionsF termined in IWWSF he teriE
funtion reltionships of single he sequening of genome is l genome onsisting of IFV milE
moleulesD iFeFD the individul n esier prt thn the underE lion nuleotides nd IDUHH genes
omp onents of iologil sysE stnding of funtionl impliE is lredy followed y the exE
temD nd they do not ontin tions of whenD whereD nd how plosion of omplete genomi seE
higher level informtionD iFeFD genes nd moleules funtion in quenes of numer of orgnE
wiring digrmsD of geneti inE living orgnismsF portuntelyD isms from teri to eukryE
tertions nd moleulr interE our knowledge of the funtionE otesF es of mid IWWTD the genome
tionsF st is ovious tht withE tht is represented y wht is pthwysD lthough we intend
out suh wiringEdigrms ioE termed inry reltionF en to omputerize other pthwysD
logil system ould never e deE exp ert in the eld would syntheE suh s signl trnsdution nd
sried or understo o dF size pthwy from olletion ell yle pthwys nd the
of inry reltions otined y geneti pthwys of the erly
e hve thus initited
exp erimentl oservtionsF sn stges in fruit y developmentF
pro jet nmed uiqqD uyoto
order to op e with the rpidE e exp et tht one suh dt
inylopedi of qenes nd
ly expnding o dy of informE re prop erly omputerizedD it
qenomesD to omputerize the
tion it is neessry to omputE will eome fesile to ssist exE
urrent knowledge of moleulr
erize the pro ess of synthesizing p erimentsD filitte understndE
nd ellulr iology in terms of
pthwysD in ddition to omE ingD nd even p erform logiE
the informtion pthwys tht
puterizing known pthwys deE l simultions of informtion
onsist of interting genes or
rived y humn exp ertsF pthwys ontrolling ll sp ets
moleulesF he si dt item
of living orgnismsF
in uiqq is pirwise interE gurrentlyD we re fo using
tion of genes or moleules our ttention on the met oli
pigure IX he home pge of the qenomexet server t httpXGGwwwFgenomeFdFjpG nd the
hfqi nd uiqq serh windowsF
qenomexet htse qenomexet under the qenome he im of qenomexet is not
snformtis ro jetD prt of the simply network onnetionY it
ervie
rumn qenome rogrm of the is to estlish the informtis
winistry of idutionD ieneD infrstruture for genome reE
sn IWWI we estlished
p orts nd gulture @wonushoAF serh nd relted reserh res
omputer network nmed
in moleulr nd ellulr ioloE ieneD the niversityofokyoD ed in the FF or iurop eF iven
gyF sn view of the susequent hs gretly ontriuted towrd the dtses whih limed to
government funding of snternet tht endF e orgnized in tpn tully
tivities in tpnD we re only hevily dep end on the systems
he most p opulr mo de
urrently mintining the onE nd proto ols develop ed in other
of ess to the qenomexet
netion etween okyoD uyoto ountriesF
dtse servie is to use our
nd pukuokF yriginllyD we enE uiqq is n ttempt to dE
server shown in pigF ID
visioned network ommunity vne our originl onepts nd
whih provides mong othersD
where the informtis needs of tehnologiesD nd tul dt
the hfqi integrted dtse
individul reserhers nd indiE olletion eortsF elthough
retrievl system nd the seE
vidul pro jets would e relized we hve not yet mde forE
quene interprettion to ols inE
on their lo l mhines y inteE ml nnounement of uiqqD
luding sequene similrity nd
grting dtses nd omputE preliminry version hs een
motif serh progrmsF he
tionl resoures distriuted over pulily ville through the
server reeives tens of thousnds
the networkF e elieve tht the qenomexet server sine
of queries p er dyD oneEthird of
wideErnging dtse servie heemer IWWSF he trget dte
whih re from rodF elE
in qenomexetD whih is jointly of the rst relese of uiqq is
though the qenomexet dtse
provided y the up eromputer yto er IWWTF e pln to disE
servie is result of tehnologE
vortory of the snstitute for triute ompt diss in ddition
il developments in tpnD for
ghemil eserhD uyoto niE to the servie over the snternetF
exmpleD hfqi ws develop ed
versity nd the rumn qenome
in my l ortoryD most of the
genter of snstitute of wedil dtses tht we oer origintE
Pathways
Binary relations KEGG Hierarchies
Genes Molecules
LIGAND
Genome OMIM DBGET CAS Databases
DNA/Protein Databases
Medline
pigure PX he onept of uiqq nd its reltion to hfqiF sn uiqq funtionl sp ets of genes
nd moleules re represented y inry reltionsD hierrhiesD nd pthwysF
e retrieved uniformly nd links he gonepts he onept of reltion nd
re mde etween relted entries dedution is thus the sis
in dierent dtsesF sn this of our uiqq pro jetF por
gurrentlyD uiqq is omp osed
lo oselyEoupled integrtionD the our logiEsed tivitiesD we
of three interonneted setionsX
shem or the formt of hown knowledge the pst oll orE
pthwysD genesD nd moleulesD
entry is orgnized y dt items tions with the pifth qenertion
whih re lso linked to
is left to eh dtseF his gomputer ro jet tem memE
numer of existing dtses
should e ontrsted with using ers in sgy nd the reserhers
through hfqi @pigF PAF
the sme reltionl dtse nd in the qenome snformtis eE
foth oneptully nd prE
enforing unied shem for serh ro jets IWWIEIWWS nd
tillyD uiqq nd hfqi
entries oming from mny dierE IWWTEPHHHF
re tightly oupled systemsF
ent souresD whih neessrily inE
hfqi provides n integrted
volves the pro ess of dt onE
view of vrious dtses in
he ehnologies
versionF
moleulr iologyD where the E
he prolifertion of
sis of integrtion is the link @iE
uiqq mkes full use of the
ws o on to our pproh
nry reltionA etween relted
dvnements in the dtse
of lo ose integrtionY the link
entries in dierent dtsesF sn
nd networking tehnologyD inE
pilities of hfqi t the
uiqqD n orgnism my e
luding dedutive nd o jetE
mehnism of very nieE
onsidered dtse of genes
oriented dtsesD the multimeE
lyF he textEsed hfqi sysE
nd gene pro dutsD nd the link
di environment of D nd
tem ws esily extended to the
etween them is used for synE
the moile gentD tvF elE
multimedi environmentD where
thesizing pthwyF husD
though we mintin the logiE
Qh grphisD Ph grphisD nd
oth uiqq nd hfqi onE
sed formlism of reltion nd
imges re now retrievle in
tin n sp et of the dedutive
dedutionD we tke prtilD
the version of hfqiF
dtse where new reltions
exile pproh in the tul
sn dditionD euse the up dte
n e dedued from reltions
implementtionF por exmpleD
pro edure do es not involve dt
stored in the dtseF
we use the gyev dedutive
onversionD hfqi hs een
enother imp ortnt onept
dtse system for exp erimentE
nd will ontinue to e le to
in uiqq is the hierrhy tht
ing the dedution pro essD ut
op e with the ever inresing
represents funtionlD struturlD
in the tul implementtion of
numer nd volume of dily upE
nd evolutionry reltionships of
uiqq we hve developed our
dted dtsesF
genes nd moleulesF por exE
own gCC lirry for mnipultE
uiqq inherits ll these
mpleD the degree of similrity
ing inry reltions nd hierrE
hfqi pilitiesF purtherE
in sequenes nd Qh strutures
hiesF
moreD the grphis hndling of
of proteins is used for lssifyE
ith similr philosophyD
pthwy digrms nd hromoE
ing sup erfmilies nd Qh foldsF
hfqi do es not dep end on
some mps hs een implementE
he txonomy is the lssiE
ny dtse mngement sysE
ed y tvF he new pilities
tion of orgnismsD whih is imE
temF he entire system hs
of logil inferene nd simulE
portnt in extending sequene
een developed in houseF etuE
tion re still under developmentD
nd Qh struturl similrities to
llyD hfqi hs its ro ots in the
ut we hop e to mke the rst
funtionl similritiesF hese
shie sequene nlysis pkE
test version ville shortlyF
nd other lssitions re tkE
ge tht s developed in the erly
en from pproprite soures nd
IWVHs in the FF xtionl snstiE
implemented in uiqqF
tutes of relthF hfqi ims t
ht golletion ifE
integrting dierent dtses hile the inry reltion
nd dierent types of dt in represents tD horizontl reE
forts
moleulr iologyF he integrE ltionshipsD the hierrhy repE
rowever eiently the system tionD howeverD is t the level of resents vertil reltionshipsF
is developed s dtseD the dt entriesY for exmpleD enE foth re nturlly integrted
most ritil thing is the quliE tries in dierent dtses n in the pro ess of dedutionF
or there is n unknown reE for there is hemil sis of ty of dt tht it ontinsF isE
tion pthwy tht utilizes dierE the inry reltion etween peillyD sine the dt we hnE
ent enzymes in the tlogF por sustrte nd pro dutF uiqq dle require iologil knowledge
the ltter p ossiilityD the deduE ontins the sustrteEpro dut in sp ei dominsD qulity onE
tion from inry reltions of suE reltionships nd the reltionE trol is fr more diult thnD for
strtes nd pro duts is usefulF sn ships of two onseutive enE exmpleD hxe nd protein seE
ny seD the pthwy informE zymes tht pp er in the known quene dtsesF emong the
tion is ritil in the nding nd met oli pthwysF mny dierent su jets of moleE
funtionl ssignment of genes in yne of the m jor o jeE ulr nd geneti pthwysD the
the genome pro jetsF metoli pthwys re proE
tives of the uiqq pro jet is
ly the esiest to omputerize
to link the struturl dt @gene
es in the sequene lignment
euse of the wellEestlished
tlogsA otined y genome
nd Qh struture lignmentD the
knowledge nd existing ompiE
pro jets nd the funtionl dt
pthwy lignment will eome
ltionsF e hve een omE
otined in sp eilized elds of
n imp ortnt to ol to identify
puterizing met oli pthwysD
moleulr nd ellulr iologyF
glol nd lo l similrities eE
in oll ortion with n exp ert
yne the genome sequening is
tween two pthwys or onE
in io hemistryD mostly from
ompleteD it is ustomry to tE
sensus mong mny pthwysF
tempt to lssify ll genes E the fo ehringer wll hrt nd
por exmpleD the omprison of
the ompiltion y the tpnese
ording to their funtionsD for exE
orgnismEsp ei pthwys will
mple in the sheme develop ed fiohemil o ietyD nd prtly
identify funtionl similrities
from other text o oks nd onEline
y woni ileyF e pln to
nd dierenesD s well s evoE
dtsesF
mke more o jetive lssiE
lutionry reltionshipsD etween
tion sed on the pthwy dt
orgnismsF feuse pthwy uiqq urrently ontins
eing enteredF et the momentD
dt re linked to diverse rnge most of the known met oli
we only p erform the lssiE
of dt in uiqq nd hfqiD pthwys represented y out
tion of enzyme genesF
they n e nlyzed in mny VH grphil digrmsF en enE
dierent p ersp etivesF por exE zyme is likle o jet in the
mpleD y exmining where the digrm to retrieve the orreE
puture hiretions
enzymes in the sme op eron pE sponding entry of the vsqexh
p er on the pthwy will give inE dtse nd thenD through
erhpsD the most hllenging
sights into the regultion of gene hfqiD numer of relted
tsk of the uiqq system is the
expressionD s well s the evoE entries in dierent dtsesF
inferene pilities tht will
lutionry implitions of gene vsqexh is dtse of enE
help humn eings to mke logE
struturesF zyme retions nd met oli
il resoning pro essesF hese
ompounds tht we orgnize in
pilities hve not yet een
he pthwy omputtions
seprte pro jetF st proE
developed or implementedD ut
desri ed ove will hve diE
vides links etween the new
here re some exmples @pigF QAF
ret prtil pplitionsD
ere dtse nd the exE
whih my e olletively lled qiven list of enzymes @ig
isting dtses of nuleotide seE
pthwy engineeringF por exmE numersA tht re found in the
quenesD mino id sequenesD
pleD from pthwy omprisons gene tlog of n orgnismD
Qh struturesD sequene motifsD
nd nlysesD n eetive p esE uiqq utomtilly genertes
mino id muttionsD geneti
tiide or sideEeet free drug the orgnism sp ei pthwys
mpsD geneti disesesD nd litE
my etter e designedF qeneti y mrking the enzymes foundF
ertureF
engineering ws sed on the henD the onnetivity nd omE
hxe sequene informtionD nd pleteness of mrked enzymes n sn ddition to omputerizE
protein engineering ws sed on e used to ssess the orretE ing known pthwysD we re deE
the protein Qh struturesF ith ness of funtionl ssignments in veloping metho ds to ompute
the vilility of new types of the gene tlogF he existene pthwys from inry reltionsF
dt on the wiringEdigrms of of missing element implies eiE he met oli pthwy is est
living systemsD pthwy engiE ther the gene tlog is wrong suited for this purp ose s wellD
neering is ound to emerge s new iotehnology in the PIst enturyF
Genome projects Biological knowledge
Binary relations and hierarchies Gene catalogs
Path computation Deduction from binary relations; gene finding and prediction.
Pathway comparison Similarities/differences with respect Pathways to species/environment.
Pathway analysis Duplication of genes; relationships with operons; etc.
Pathway engineering Design of new pathways and
compounds.
pigure QX thwy engineering will eome fesile one dt nd knowledge re prop erly omputerE ized nd new omputtionl metho ds re developedF