生物信息學(xué)第三講基因功能富集分析

基因功能富集分析廖奇寧波大學(xué)醫(yī)學(xué)院Gene

OntologyGene

Ontology(GO)提供目前可獲得的基因或基因產(chǎn)物的功能，是一個可計算知識的最全面的資源，主要包含兩大方面：Gene

Ontology生物功能（terms）之間的邏輯結(jié)構(gòu)和它們之間的關(guān)系，表現(xiàn)為有向無環(huán)圖（directedacyclic

graph）。GO注釋基因產(chǎn)物(aprotein,non-coding

RNA,ormacromolecular

complex)對應(yīng)的功能。GO注釋涉及140000篇發(fā)表文獻(xiàn)的實驗發(fā)現(xiàn)，600000實驗支持的GO注釋條目。這些作為核心知識，用于其他超過600萬來自不同物種的功能注釋的推斷。GO聯(lián)合會(GOConsortium，GOC，/)也提供軟件用于編輯和執(zhí)行GO本體的邏輯推理、提供訪問GO本體和注釋的網(wǎng)上接口、提供基于GO知識支持生物醫(yī)學(xué)研究的分析工具。各物種實驗驗證和非實驗驗證注釋條目的數(shù)目GO類別GeneOntologyBiology

Process生物過程Molecular

Function分子功能Cellular

Component細(xì)胞組分GO類別分子功能：由基因產(chǎn)物所執(zhí)行的分子水平上的活性單個大分子本身的活性或功能，通常通過與其他分子的物理相互作用來實現(xiàn)。主要包含兩大功能：(1)生化活性，(2)作為一個大的系統(tǒng)或過程的組成部分細(xì)胞組分：基因產(chǎn)物實現(xiàn)功能所在的細(xì)胞結(jié)構(gòu)上的定位當(dāng)基因產(chǎn)物執(zhí)行其功能時，所處的相對細(xì)胞組分和結(jié)構(gòu)上的位置。主要有兩種：（1）相對于細(xì)胞結(jié)構(gòu)（例如，質(zhì)膜的細(xì)胞質(zhì)側(cè)）或隔室（例如線粒體），（2）穩(wěn)定的大分子復(fù)合物的一部分（例如核糖體）。與GO的其他方面不同，細(xì)胞組分不涉及過程，而是細(xì)胞解剖學(xué)。生物過程：由多個分子一起完成的生物程序、系統(tǒng)的過程。生物過程通常以其結(jié)果或終止?fàn)顟B(tài)來描述，例如，細(xì)胞分裂的生物學(xué)過 程導(dǎo)致從單個母細(xì)胞產(chǎn)生兩個子細(xì)胞（分裂細(xì)胞）。生物過程是由一組特定基因產(chǎn)物（或大分子復(fù)合物）所執(zhí)行的，通常被 高度調(diào)節(jié)，且在特定的時間點進(jìn)行。Molecular

Function What

does

it

do?Biological

Process What

process

is

it

involved

in?Cellular

Component Where

does

it

act？早老素1蛋白在阿爾茨海默病中促進(jìn)淀粉樣前體蛋白的產(chǎn)生，導(dǎo)致淀粉樣斑塊的生成和神經(jīng)纖維纏結(jié)的形成Beta-amyloid

formationCell

differentiationNeurotransmission regulationBrain

developmentPSEN1Biological

ProcessMolecular

FunctionCellular

ComponentTransmembrane transportTranscription

factor bidingKinase

activityGamma-secretase complexDendritic

rootsRegulatory

protein complexes把GO當(dāng)作圖GO的結(jié)構(gòu)可以用圖的項（terms）來描述，每個GOterm代表一個節(jié)點，而terms之間的關(guān)系用節(jié)點間的邊來表示。GO

的結(jié)構(gòu)是垂直而松散的子（child）節(jié)點相對于父（parent）節(jié)點的功能更加專一。父節(jié)點代表與圖中根節(jié)點更近的節(jié)點，而子節(jié)點則更接近葉節(jié)點，因此，父節(jié)點所對應(yīng)的描述更加寬泛，而子節(jié)點則更加專一，箭頭代表關(guān)系的方向。點線表示推斷的關(guān)系，而實線表示注釋的關(guān)系。一個子節(jié)點可以有超過2個或以上的父節(jié)點。比如：mitochondrion

有2個父節(jié)點:organelle

（細(xì)胞器）以及cytoplasm

（細(xì)胞質(zhì)）;而organelle

有2個子節(jié)點:mitochondrion,以及organelle

membrane又比如：Part

ofIs

aGO

terms之間的關(guān)系is

a

(is

a

subtypeof)part

ofhas

partRegulatesnegatively

regulates

and

positively

regulates.GO功能之間的關(guān)系可以利用AmiGO

and

QuickGO

來查看。is

a

和part

of表示子節(jié)點所描述的功能、細(xì)胞組分或過程從始至終都是屬于父節(jié)點的， 為is

a，否則，只有其中一部分是屬于父節(jié)點的，則part

of。三個本體中（分子功能、細(xì)胞組分和生物過程）不會出現(xiàn)isa關(guān)系 的交叉，而part_of

和regulates

則在不同的GO本體中會有交叉。比如，分子功能‘cyclin-dependent

protein

kinase

activity（細(xì)胞周期蛋白依 賴性蛋白激酶活性）’是part_of

生物過程‘cell

cycle’。is

a

關(guān)系為GO結(jié)構(gòu)的基礎(chǔ)如果說AisaB，我們說A是B的亞類型.比如“mitoticcellcycle（有絲分裂細(xì)胞周期）”

is

a

“cellcycle”，或者“l(fā)yase

activity（裂解酶活性）”

is

a“catalyticactivity（

化活性）”注意：is

a

不代表‘is

an

instance

of’。Instance為例子，比如a

cat

is

amammal，但是Garfield

is

an

instance

of

cat，而不是a

subtype

of

cat。不過，如果我們說cat

is

a

mammal，那么every

instance

of

cat

is

amammal.regulates

關(guān)系包含兩種，positively

regulates

和negatively regulates。haspart：是partof的互補(bǔ)邏輯，從父節(jié)點的角度來說部分—整體 的關(guān)系。pigment

metabolic

processduring

pigmentationpigment

metabolic

processduring

developmentalgmentationcellular

componentpigmentation

duringdevelopmentduringdevelopmentnegative

regulation

ofpigmentatan

duringdevelopmentbiological

processmolecular

functionregulation

aT

biological

processnegative

regulation

ofbialogica!

processpositiveregulation

aT

biologicalprocesseye

pigmem

precursortransportpositive

regulation

ofpigmentatan

duringdevelopmentnegative

regulatian

al

cuticlegmentatiannegative

regulatian

al

eyegmentatianpositive

regulatian

aT

cuticlepigmentatanpositiveregulatian

al

eyegmentatianis

a

&is

a

→

is

aif

A

is

a

B,

and

B

is

a

C,

we

caninfer

that

A

is

a

C.“mitochondrion”isan“intracellularorganelle（胞內(nèi)細(xì)胞器）”， 而“intracellular

organelle”is

an

“organelle”，因此

mitochondrion

is

an

organelle.如何推斷GO

term之間的關(guān)系is

a

&part

of

→

part

ofif

A

is

a

B,

and

B

is

part

of

C,A

is

part

of

C.（如果關(guān)系的順序相反，結(jié)果也是一樣的）比如“mitochondrion”is

a

“intracellular

organelle”，而

intracellular

organelle

is

part

of

cell，因此，mitochondrion

is

part

of cellpart

of&part

of

→

part

ofif

A

part

of

B

part

of

C

then

A

part

of

C比如，“mitochondrion”is

part

of

“cytoplasm”，而“cytoplasm”is

part

of

“cell”，因此mitochondrion

is

part

of

cell關(guān)于part

of

和is

a

關(guān)系的邏輯推理，與中間的is

a

和partof

關(guān)系 的數(shù)目無關(guān)。part

of&is

a

→

part

of if

A

is

part

of

B,

and

B

is

a

C,

we

caninfer

that

A

is

part

of

C.比如,“mitochondrial

membrane

（線粒體膜）”part

of mitochondrion,而mitochondrionis

an

intracellularorganelle，因此

“mitochondrial

membrane”is

part

of

“intracellular

organelle

”。has

part

&has

part

→

has

part if

A

has

part

B,

and

B

has

part

C,we

can

infer

that

A

has

part

C.比如:“spliceosomal

complex

（剪接體復(fù)合體）”has

part “U4/U6

x

U5

tri-snNRP

complex”，且“U4/U6

x

U5

tri-snNRP complex”has

part

“snRNP

U5”，因此，spliceosomal

complex has

part

snRNP

U5

。has

part&is

a

→

has

partIf

A

has

part

B,

and

B

is

a

C,A

has

part

C

（關(guān)系順序相反，結(jié)果一樣）比如:

“precatalytic

spliceosome

（預(yù)

化剪接體）”

has

part “snRNP

U5”，而

“snRNPU5”

is

a

“small

nuclear ribonucleoprotein

complex

（小核核糖核蛋白復(fù)合體）”，因此， “precatalytic

spliceosome”

has

part

“small

nuclear ribonucleoprotein

complex”is

a

&has

part

→

has

part if

A

is

a

B,

and

B

has

part

C,A

has

part

C.比如“U2-dependent

activated

spliceosome（

U2依賴性激活剪接

體）”is

a

“activatedspliceosome”，且“activatedspliceosome” has

part

“snRNP

U5”，因此，“U2-dependent

activated spliceosome”has

part

“snRNP

U5”。regulatesif

A

positively

regulates

X,

it

is

true

to

say

that

A

regulates

X.A

positively

regulates

X,

so

it

also

regulates

X;

B

negatively

regulates

X,

so

it also

regulates

X.互補(bǔ)減數(shù)分裂重組的激活減數(shù)分裂重組檢查點注意：如果X

注釋為regulates

glycolysis的過程，不能推斷X

is involvedin

glycolysis。regulates&is

a

→

regulatesIf

A

is

a

B,and

B

regulates

C，we

can

infer

that

A

regulates

C.This

rule

is

true for

positively

regulates

and

negatively

regulates.（調(diào)換順序，結(jié)果一樣）“negative

regulation

of

M

phase”is

a

“negative

regulation

of

cell cycle

process”,而negative

regulation

of

cell

cycle

process”

negatively

regulates

“cell

cycle

processes”;因此“negative regulation

of

M

phase”negatively

regulates

“cell

cycle

processes”。“negative

regulation

of

M

phase”negatively

regulates

“M phase”，而“M

phase”isa

“cell

cycle

process”，因此，

“negative

regulation

of

M

phase”negatively

regulates

“cell

cycle processes”.regulates&part

of

→

regulatesif

B

is

part

of

C,

any

A

thatregulates

B

also

regulates

C.“regulation

of

mitotic

spindle

organization（有絲分裂紡錘體組成的 調(diào)節(jié)）”regulates

“mitotic

spindle

organization”，而“mitotic

spindle

organization”is

part

of

the

“mitotic

cell

cycle”，因此 ，“regulation

of

mitotic

spindle

organization”regulates

the

“mitotic

cell

cycle”。positively

regulates

&

part

of

→

regulatesnegatively

regulates

&

part

of

→

regulatespart

of

∘regulates

→

???凋亡誘導(dǎo)過程中蛋白質(zhì)插入線粒體膜regulation

of

anti—R

+—8B

—9-????

?regulation

ofapoptosisis

a∘

...part

of

∘

...regulates

∘

...positively

regulates

∘

...negatively

regulates

∘

...has

part

∘

...GO

ID命名每個GO

term有一個名字：如mitochondrion,glucose

transport, amino

acid

binding。GOID為前綴為GO:，后面加七位0填充的標(biāo)識符(oftencalled

the term

accession

or

term

accession

number)如GO:0005125

或GO:0060092.ID

的數(shù)字部分與這個term所處位置或意義無關(guān)。通常GOID的某一范圍被 指定給每個本體的編輯或者編輯團(tuán)隊，因此，GO

ID可以追溯誰添加的。Ontology

更新由GOC

ontology

團(tuán)隊和請求更新的科學(xué)家完成。大 部分請求來自GO功能注釋的科學(xué)家（只是影響少數(shù)GO

terms）， 而特定生物領(lǐng)域中研究功能域的專家可能影響本體中包含很多GO terms和關(guān)系的整個分支。GOC邀請研究者和計算機(jī)科學(xué)家提交更新本體中GOterms和其之 間關(guān)系的請求。GO的更新GO的基因注釋可信等級來自/page/evidence-code-decision-tree3.5

M1.5MExperimental

annotations

by

speciesAn

notations

by

evid

encee^cgvidenceAnnotad

ons160k140k1

2Ok1D0k60k40kAnnotations

by

aspect/species

by

eviden

cesimilaritYevidenceexperimental

evidencecurator

inference

author

statementcombinatarial

evidencegenDmic

context

evidenceGO

Slim:關(guān)于GO的縮減版本，間單地講，為簡化的Gene本體、簡化GO

的注釋結(jié)果，將所有的GO注釋歸類到指定的數(shù)個GO

功能分類上。AmiGOQuickGOGO

term查詢GOIDGO

term名字GO

term描述對應(yīng)基因的注釋條目（所有物種）該GO

term的同義詞語GO

term之間的關(guān)系子節(jié)點（GO）由UniProt-GOA提供的認(rèn)為利用IEA方法獲得的錯誤注釋列表與該GO共同出現(xiàn)的GO

term同時出現(xiàn)的次數(shù)比較的GO

term出現(xiàn)的次數(shù)概率比概率相似度比該GO信息更改的日志518個對應(yīng)基因的注釋條目（涉及所有物種）序列ID基因名該基因與該GO的關(guān)系注釋該條關(guān)系的參考信息物種ID注釋該條關(guān)系的組織提供518個注釋條目的統(tǒng)計信息證據(jù)參考信息物種注釋的組織或機(jī)構(gòu)GO對應(yīng)的類別查詢基因的GO注釋信息NCBI

Entrez

Gene

（所有物種）GeneCards

（物種人）NCBI

Entrez

Gene的結(jié)果ProcessDNAdamage

response.

s

gnat

transduction

b\'

p53

class

mediator

DNA

damage

response,

signal

transduction

by

p53

class

mediatorDNS

damage

response,

signal

transduction

b}'

p?3

class

mediator

resulting

in

c.°.II

r}'ce

arrest

DNA

damage

response,

signal

transduction

b\'

P?3

class

mediator

resulting

in

call

cycle

arrestDNA

damaga

response.

signaltransduction

by

p?3

class

mediator

resulting

in

transrrintion

ofP21

class

mediator

DNA

damaga

response,

signaltransduction

b}'

p?3

class

mediator

resulting

in

transrrintion

of

p21

class

mediator

DNAstrand

renaturatinnER

n\'arInad

rc'sponsaRNA

PaivnJerase

II

trannr:rintionaI

nreinitiatian

cnmplex

as

sniJJbIy

Ras

protein

signal

transductionautoDhagyb

tSr'-e?cixiDn

r*pair

cell

ag

gc=Il

cycle

arrest

r°I1

cycle

arr°st

cell

diP

rentiation

c°Il

proliferationcellular

respDnsc

tO

DNA

daiJJaoe

stimulus

cellular

renpDnse

to

DNA

danJaoe

stimulus

Call

lar

ren0Dnse

to

UVcallclar

resgnnse

to

afiinnmycin

D

cellular

respDnse

to

drugc.°.IIuIar

respDnse

to

gamma

radiatinn

cellular

respDnse

to

glucose

star\’atinn

c.=.IiuIar

resPDnse

to

hypaxiaItems

1

-

26

of

94Items

1

-

25

of

94Last

>>PribMed

PribMed

PubMed

PubYedPage

.1"

”.

of

4

Next

>Evidence

Code

PubsIDA

PubMedIMP

PubfiedlIvIP

PuhfiedTAS

IDAIIvIP

IDAIDAIEAIEPlIvIP

TAS

IhIPIDAlk'IPTAS

TAS

IDAlIvIPIDA

IDA

IEPIDA

IDA

IEPPaQe

1Puhfied

Puhfied

PrihMed

PribMed

PribV?J

PubMeJ

Puh'Ued

PubMed

Pubfied

Puhfied

PrihMed

PribMed

PribMed

PubMed

PubYed

PubMedof4

Next°ComponentPML

bodyC\/t0DlgSlTl

E}10|)@SUcVlOS0

EXOSOIendoplasmic

reticulumintracellular

mitochondrial

mabix

mitoch0ndrion

colocalizes

w'ith

nudear

body

nuclear

chromatinnuclear

matrix

nucleolus

nucleoplasm

nucfeoplasm

nucleus

nucleusprotein-containing

complex

protein-containing

complexcolocalizes_w'?h

transcription

factor

TFllD

E0mplexEvidence

CodeIDA

IDA

IMP

IDA

TASiEAIDAiEA

IDA

IDA

IDA

IDA

IDA

IDA

TAS

IDA

IMP

IDA

IMP

IDAPubsPubMed

PubMed

PubMed

PubMedPubMedPubMed

PubMed

PubMed

PubMed

PubMed

PubMedPubMed

PubMed

PubMed

PubMed

PubMedGeneCards的結(jié)果Irene

Ontology

(GD)

?

Biological

Process

tor

Tf'53

Gene

?*}85

iesillls)

See

all

85

?GO

IDQualifiedGO

ter?iEviderxwPubMad

IOeGO:0000122negative

regulation

oftranscription

by

RNA

polymerase

IIISS1674B7B1GO:0000735DNA

strand

renaturationIDA8183576GO:0006284base-excision

repairTAS15116721GO:000628Bnucleotide-excision

repaifIMP7683514GO:00063fi1transcription.

DNA-temp

ttedIEAGeneSLik9M9

Genes

that

share

ontologies

with

TP53:

viewGene

Ontology

(GO)

-

tellular

Com#ortenls

for

TP53

Gene

?4}(18

results)

See

less

+GO

IDQua1ifiad

GO

ternEvidozxwPubMedIOsGO:0000700nuclearchromatinIDA15710328GO:0005822intracellularIDA16213212GO:0005834nucleusIMP,IEA18479015GO:0005854nucleoplasmTAS.IDAGO:0005857replmation

larkIBAGO:0005886calocalizes

nith

transcription

factor

TFIID

complexIDA1505387BGO:0005730nucleolusIDA12080348GO:0005737cytoplasmIEA,IMP16479015GO:0005736mitochondrionIDA,IEA12807443“KEGGKEGG（京都基因與基因組百科全書），是基因組破譯方面的數(shù)據(jù)庫。是了解高級功能和生物系統(tǒng)（如細(xì)胞、生物和生態(tài)系統(tǒng)），從基因組到分子水平信息，尤其是大型分子數(shù)據(jù)集生成的基因組測序和其他高通量實驗技術(shù)的實用程序數(shù)據(jù)庫資源，由日本京都大學(xué)生物信息學(xué)中心的Kanehisa實驗室于1995年建立。是國際最常用的生物信息數(shù)據(jù)庫之一，以“理解生物系統(tǒng)的高級功能和實用程序資源庫”著稱。https://www.kegg.jp/來自https://paintomics.readthedocs.io/en/latest/1_kegg/主要包含基因和蛋白質(zhì)的分子構(gòu)建塊（基因組信息）以及分子通路圖中被整合進(jìn)相互作用、反應(yīng)和關(guān)系網(wǎng)絡(luò)（系統(tǒng)信息）的化學(xué)物質(zhì)（化學(xué)信息），而且還包含疾病和藥物信息（健康信息）KEGG系統(tǒng)信息基因組信息化學(xué)信息健康信息進(jìn)一步可細(xì)分為18個主要的數(shù)據(jù)庫?？梢酝ㄟ^不同的顏色編碼來區(qū)分。CategoryDatabaseContentColorSystemsKEGG

PATHWAYKEGG

pathway

mapsinformationKEGG

BRITEBRITE

hierarchies

and

tablesKEGG

MODULEKEGG

modulesGenomicKEGG

ORTHOLOGY

(KO)Functional

orthologsinformationKEGG

GENOMEKEGG

organisms

(complete

genomes)KEGG

GENESGenes

and

proteinsKEGG

SSDBGENES

sequence

similarityChemicalKEGG

COMPOUNDSmall

moleculesinformationKEGG

GLYCANGlycansKEGG

REACTIONBiochemical

reactionsKEGG

RCLASSReaction

classKEGG

ENZYMEEnzyme

nomenclatureHealthKEGG

NETWORKDisease-related

network

elementsinformationKEGG

VARIANTHuman

gene

variantsKEGG

DISEASEHuman

diseasesKEGG

DRUGDrugsKEGG

DGROUPDrug

groupsKEGG

ENVIRONHealth-related

substancesDatabaseObjectPrefixExamplepathwayKEGG

pathway

mapmap,

ko<org>map00010map00010ec,

rnhsa04930hsa04930briteBRITE

functional

hierarchybr,

jp<org>br:08303br08303kobr:01002ko01002moduleKEGG

moduleM<org>_MM00010M00010koKO

functional

orthologKK04527genomeKEGG

organismTT01001

(hsa)ID通常前綴(complete

genome)genes<org>Gene

/

proteinhsa:3643vgvg:155971agag:CAA76703compoundSmall

moleculeCC00031glycanGlycanGG00109reactionReactionRR00259rclassReaction

classRCRC00046enzymeEnzymeec:networkNetwork

elementsNN00002variantHuman

gene

variantshsa_var:25v1diseaseHuman

diseaseHH00004drugDrugDD01441dgroupDrug

groupDGDG00710environHealth-related

substanceEE00048+5個數(shù)字KEGGPATHWAY數(shù)據(jù)庫是一個手工畫的代謝通路的集合，包含以下 幾方面的分子間相互作用、反應(yīng)、代表細(xì)胞和物種系統(tǒng)功能的關(guān) 系網(wǎng)絡(luò)：新陳代謝、遺傳信息加工、環(huán)境信息加工、細(xì)胞過程、 生物體系統(tǒng)、人類疾病、藥物開發(fā)。分子相互作用、反應(yīng)和代表細(xì)胞和物種系統(tǒng)功能的關(guān)系網(wǎng)絡(luò)KEGG

Data

base

as

of

2CI

18/”8/

1

5

E

vste

rns

in

fo

re

ati

an

KEGG

PATH

\".’AYKE

VG

BRITEKE

VGF?1C

DU

LEPa

China

y

na

a

p

s,

refe

ren

ce

(CoCa

I}

FunoCio

n

al

hie

ra

rc

h

ies,

refe

rev

ce

{t

DtBI)KEGG

madu

Ies,

refe

renc

e

?{totaI/iGenomic

in

fa

rmaEio

nKE

VG

G

RTH

U

LV

G

Y

KEGG

OWhs

Iog

v

?{

KO)

g

rou

psKEGG

GENWh1EKEGG

organisrn

s

and

selected

viru

se

s(44

3

eukaryDLes,

4B26

bacte

ria,

274

a

rchaea,and

3

2ó

v

iruses)Gen

es

in

KEGG

organi:s

m

s

an

d

ot

h

er

c

ate

go

ries(in

cl

ud

in

g

4,

3

5D

a

dd

end

u

m,

3

1

B,

7

64

vi

ra

\)(s

e

e

an

r

o

tati

c

r-

sta*.istic

s)Best

hit

relations

xvithin

GENESBi—dire

cCion

al

best

h

it

relations

wit

hin

GENESK

EG

G

G

E

NENK

E

SG

S

S

C

B5

29

(

5

1,

99

1

}20

3

(

2

1

,

B2

1

)79

9

d

B

D,94

7)Z,871231,8O3,?

33,B3113,373.90

8,B16Claemica

I

inforns

ationFI

eCa

b

DIIUS

3

ft

d

at

h

er

s

m

ali

m

ol

e

cu

IesGDY*

*Bia

ch

e

m

ina

I

re

a

ctian

sReaCtiDF+

CI

as

sE

n

zy

m

e

na

m

en

cTat

u

reKEC2G

CO

f4

POU

NDK

E

EG

G

LYC1NKEC2G

REACTIC

N

K

E

GG

RC

USBKEGG

EN*Y!'HEHeaft

h

info

i-m

atiar

KEGG

N

'?'?'OR

KKEC2G

1*A

R￡ANTKESG

DIS

EFSEKEC2G

D

R?JGKEC2G

D

C2

GC2UPKESG

ENY''JDG

ND

ru

g

Ia

b

e

IsDis

ease-relate

d

n

etv'z

orkHu

man

g

e

ne

na

rianCsHuns

an

d

isea

sesDru

gsDz

g

g

ro

u

psel

e

me

n

CsC

ru

de

d

ru

gs

an

d

h

ealt

h-

re

IaCed

su

bstan

cesJapan

e

se

pres

cription

drug

Iab

eIs

frDm

J?PICapan

ese

OTC

drug

I

abe

Is

Prorri

JAPICFDA

presc

riptiDW

dru

g

Iab

el

s

lin

ke

d

to

D

aiI

'I-1edFDA OTC

d

ru

g

Iabel

s

lin

ked

Eo

D

a

ile

F?1e

dKESG

F-1ED

ICU

SKESG

F?1ED

ICUS18,379ii,O&81O,99<3,1267,354471169Z,16O1O,Z3ZZ,O9683614,42011,1M93A,911KEGG

PATHWAY–由2-4字母的前綴+5個數(shù)字代表，前綴意義如下:map-Reference

pathway(map)：參考通路圖ko-Reference

pathway(KO)：基因ec-Reference

pathway(EC)：酶rn-Reference

pathway(Reaction)：反應(yīng)org-Organism-specificpathway

map

：物種特異的通路圖僅僅第一種參考通路(referencepathway)圖是手動繪制的，其他的通路圖都是通過計算產(chǎn)生的.對于代謝通路圖中，每個盒子（或線）對應(yīng)Knumber(KOidentifeir，基因),the

EC

number（酶）,and

the

R

number(reactionidentifier，反應(yīng)).而KO,EC,和reaction

maps

只對應(yīng)它自己的內(nèi)容，如基因或酶或反應(yīng).對于所有的代謝和非代謝通路，K標(biāo)識符被認(rèn)為是基因，可以將其轉(zhuǎn)化為物種的某個基因，用來產(chǎn)生物種特異的通路圖.map00010ko00010hsa00010“map”通路不標(biāo)注顏色，“ko/ec/rn”通路標(biāo)注為藍(lán)色，而物種特異的通路標(biāo)注為綠色

在完整的整個代謝通路圖中，“map”pathways被完全著色，而“ko/ec/rn”pathways和organism-specific

pathways

如果沒有著色，則表示缺乏對應(yīng)的對象。圖的符號含義circles

-

other

molecules,

usually

chemical

compounds

identified

by

C numbers,

but

including

glycans

identified

by

G

numberslines

-

reactions

identified

by

R

numbers

in

metabolic

maps;

ortholog (KO)

groups

identified

by

K

numbers

in

global

metabolism

mapsand

in

organism

specific

pathway

maps

that

are

computationally generated:

boxes

-

genes

or

gene

products

identified

by

the combination

of

the

KEGG

organism

code

and

gene

identifiersThese

map

objects

can

be

searched

in

the

search

box

at

the

top

of

the KEGG

PATHWAY

page,

in

the

search

box

in

each

pathway

map,

and

by the

KEGG

Mapper

tools.KEGG

BRITE層級分類表包含了許多不同的關(guān)系類型。例如，可以查詢酶和底物之間的關(guān)系，也可以查詢某種酶的同源基因用層級關(guān)系結(jié)構(gòu)的文件保存，（

htextfile），每行第一個字符為“A”,“B”,“C”,等，表示層級等級，低級別的內(nèi)容可能包含很多tab空格.KEGG

MODULE

：人工定義的功能單元集合，用于解釋基因的高通量數(shù)據(jù)集的生物意義1.通路模塊：代表在KEGG代謝通路圖中的復(fù)雜功能單元，例如

M00002(糖酵解，與三碳化合物相關(guān)的核心模塊)2.結(jié)構(gòu)復(fù)合物：通常形成分子機(jī)械，例如M00072(寡糖轉(zhuǎn)移酶)3.功能集：基本單元的其他形式，例如M00360(氨?；?tRNA合酶，原核生物)4.特征模塊：作為某種表型的標(biāo)記，例如M00363(腸出血性大腸桿菌致病性特征，志賀毒素)每個BRITE

hierarchy

文件用2-4

letter

code

和5

digit

number

標(biāo)識， 前綴意思如下:br

-

Reference

hierarchyjp

-

Reference

hierarchy

in

Japaneseko

-

Reference

hierarchy

(KO)org

-

Organism-specifichierarchy“ko”hierarchy

file

是手動建立的關(guān)于基因和蛋白（用K

numbers表 示）的功能分類，而Organism-specifichierarchy

files

由計算機(jī)自動 將K標(biāo)識符轉(zhuǎn)化為物種對應(yīng)的基因產(chǎn)生。The“br”hierarchy

file是化合物、反應(yīng)、藥物、疾病和物種的功能 分類，用KEGG標(biāo)識符，而不是K標(biāo)識符。ko編號表示一個通路，這個通路是不分物種的，相當(dāng)于所有物種 的這一通路的并集。K編號表示一個基因，是ko通路中的基本單位，某一K編號代表的 不是某一具體物種的基因，而是所有物種的某一同源基因的統(tǒng)稱KEGG

通路查詢EntryThumbnail

ImageNaweDescriptionObjectLegendhsa04110C

ell

cycle

—

Horrosa

pie

ns

(hurro

n)Mito

tic

e

I

cde

progression

isaccompls

he

d

throug

h

are

producibe

seque

n?

ofevents,

DNA

repic......ysis

hsa04010:

MAPK

sipnalinppathway

hsa04110:

CeII

cycle...4,6

CycH

CycA

CycE

CycD

MAPKsignalinp

pathw

ay

CELL

CYCLEMad1

MEN

Bub2

Mps1

p21

p27,57p16

Securi...hsa05100.

Ig

tBacerial

invasion

ofepithelial

ceIIs

-

Homosapiens(hum)...creria

can

invade

phagocyticand

no

n—phapocytic

cells

andcolonize

them

intracellularly,the

n

become......M01}

hsa05100:

Bacterialinvasion

of

e

pithelial

cellshsa04512:

ECM-rece

ptorinteraction

nsa04810:

R...BACTERJAL

INVASIO

N

OFEPITHELIAL

CELLS

ECM-receptorinteractio

n

Regulatio

n

o

f

amincytos

k...Numbe

r

ofentries

in

a

pagePage

:

GO

gf

4heu

ide

a

Items

:1

-

20

of

80

Pre

o

s

|Next

iHomo

sapiens

{hurr?n)0cfHh

DNU60r

tx0P

'0UP

'U0ü00?UuH'NQnDrtDb'0??P

'u

attZl(D

?

tl

tl

4

0Hh

0

0

0

nH

n

tl

tl

40

0tl

'

0

0

0

0tto

C

?0

O

F'F'wC

?

oo?H

'

w'v)

O4(DH

1DMhW<00d(DOF0H*

D9l2O

Cosmetic

Information*

D9l3DeavironmentaJL'#

O9l4D

Ceiluiar*

D9l4land*

DBI43

Ceiiand

deathcycie

PATH:hsaD4l1DJcycie

—

yeastcycie

—

Caaiobacter—

yeastCeiiCeiiCeiiD4l1DD4l11D4l12D4l13**

D4l14D421DD4214D4215D421&D421DD4l15D421Bmeiosis

PATH:hsaD41l4jPATH:hsaD421Dj—

fiy—

maitipie

species

PATH:hsaD42l5PATH:lisaD4216jPATH:hsaD4217jp53

sigziaiing

pathway

PATH:lisaD4ll5jCeiiuiar

semesceace

PATH:hsaD42lBj*

DB144Ceiiuiar

—*

D9l45Ceiiuiar*

DBl42

Ceii*

O915D

OrgaaismaiSystems^?

D

B1

B

Dzacluded

in

PathwaywriteReferencePROD

:15568976AuthorsStegneier

F,

Amon

AT1t1eClosing

mitosis:

the

functions

of

the

Cdcl4

phosphatase

and

itsregulation.JournalAnnu

Rev

Genet

38:263-32

(2064)DOI:

18.

1146/annurev

.

genet

.

38.

872982

.

893851ReferencePROD

:9618481AuthorsXoustakas

A,

Kardas

sis

DTitleRegulation

of

the

human

p21/hAF1/Cip1

promoter

in

hepatic

cells

byfunc

t1ona

1

interact

ions

between

Sp1

and

Snad

family

members

.JournalProc

Natl

Acad

Sci

U

S

A

95:

6733-8

(1998)D01:16.1073/pna

s

.95.12.6733KO

pathwayko04110Other

DBs8SID:

83054G0

:

66662780rgan1snHonosapiens(hunan)

[GU:hsa]Gene595CCND1;cyclinD1

[K0:K64565]894CCND2;cyclinD2

[KO:K10151]896CCND3;cyclinD3

[KO:K10152]1819CDk4;eye

linéepenéent

tins

se

4

[fi0:

k82889]

[fi￡

:2.7.11.

22]1821CDk6;eye

linéepenéent

tins

se

6

[fi0:

fi82891]

[fi￡

:2.7.11.

22]GeneCDKN2A

(polymorphism)

[HSA:1029]

[KO:K06621]CDKN2B

(polymorphism)

[HSA:1030]

[KO:K04685]IGF2BP2

(polymorphism)

[HSA:10644][KO:K17392]CAPN10

(polymorphism)

[HSA:11132]

[KO:K08579]SLC30A8

(polymorphism)

[HSA:169026]

[KO:K14695]JAZF1

(polymorphism)

[HSA:221895]

[KO:K19495]HHEX

(polymorphism)

[HSA:3087]

[K0:K08024]KCNJ11

(polymorphism)

[HSA:5767]

[KO:K05004]KCNQ1

(polymorphism)

[HSA:3784]

[KO:K04926]MTNRIB

(polymorphism)

[HSA:4544]

[KO:K0A286]N0TCH2

(polymorphism)

[HSA:4853]

[KO:K20994]ENPP1

(polymorphism)

[HSA:5167]

[KO:K01513]PPARG

(polymorphism)

[HSA:5468]

[KO:K08530]CDKAL1

(polymorphism)

[HSA:54901]

[KO:K15865]ADAMTS9

(polymorphism)

[HSA:56999][KO:K08624]HNFIB

(polymorphism)

[HSA:6928]

[KO:K08034]TCF7L2

(polymorphism)

[HSA:6934]

[KO:K04491]WFS1

(polymorphism)

[HSA:7466]

[K0:K14020]FTO

(polymorphism)

[HSA:79068]

[KO:K19469]DrugInsulin

human

[DR:D03230]Insulin

lispro

[DR:D04477]Insulin

aspart

[DR:D04475]Insulin

glulisine

[DR:D04540]Insulin

glargine

[DR:D03250]Insulin

detemir

[DR:D04539]Other

DBsICD-11:

5A11ICD-10:

E11MeSH:

D003924OMIM:

125853

601283Refer

encePMID:19749172Aut:horsStaiger

H,

Machicao

F,

Fritsche

A,

Haring

HUT1t:IePathomechanisms

of

type

2

diabetes

genes.3ou

rna1Endocr

Rev

30:557-85

(2009)DOI:10.1210/er.2009-0017ReferencePMID:18782870AuthorsFlorez

JCT1t1eClinical

review:

the

genetics

of

type

2

diabetes:a

realisticappraisal

in

2008.3ou

rna1J

Clin

Endocrinol

Metab

93:4633-42

(2008)DOI:10.1210/jc.2008-1345ReferencePMID:18762020AuthorsDoria

A,

Patti

ME,

Kahn

CRTitleThe

emerginggenetic

architectureof

type

2

diabetes.3ou

rna1Cell

Metab

8:186-200

(2008)D0I:10.1016/j.cmet.2008.08.006Drug

targetomacetax1ne

aepesucc

1nate:

008956BriteKEGG

Orthology

(KO)

[BR:hsa00001]09130

Environmental

Information

Processing09132

Signal

transduction04310

Wnt

signal