基因功能富集分析廖奇寧波大學醫學院Gene

OntologyGene

Ontology(GO)提供目前可獲得的基因或基因產物的功能，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）之間的邏輯結構和它們之間的關系，表現為有向無環圖（directedacyclic

graph）。GO注釋基因產物(aprotein,non-coding

RNA,ormacromolecular

complex)對應的功能。GO注釋涉及140000篇發表文獻的實驗發現，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聯合會(GOConsortium，GOC，/)也提供軟件用于編輯和執行GO本體的邏輯推理、提供訪問GO本體和注釋的網上接口、提供基于GO知識支持生物醫學研究的分析工具。各物種實驗驗證和非實驗驗證注釋條目的數目GO類別GeneOntologyBiology

Process生物過程Molecular

Function分子功能Cellular

Component細胞組分GO類別分子功能：由基因產物所執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。主要包含兩大功能：(1)生化活性，(2)作為一個大的系統或過程的組成部分細胞組分：基因產物實現功能所在的細胞結構上的定位當基因產物執行其功能時，所處的相對細胞組分和結構上的位置。主要有兩種：（1）相對于細胞結構（例如，質膜的細胞質側）或隔室（例如線粒體），（2）穩定的大分子復合物的一部分（例如核糖體）。與GO的其他方面不同，細胞組分不涉及過程，而是細胞解剖學。生物過程：由多個分子一起完成的生物程序、系統的過程。生物過程通常以其結果或終止狀態來描述，例如，細胞分裂的生物學過 程導致從單個母細胞產生兩個子細胞（分裂細胞）。生物過程是由一組特定基因產物（或大分子復合物）所執行的，通常被 高度調節，且在特定的時間點進行。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淀粉樣前體蛋白的產生，導致淀粉樣斑塊的生成和神經纖維纏結的形成Beta-amyloid

formationCell

differentiationNeurotransmission regulationBrain

developmentPSEN1Biological

ProcessMolecular

FunctionCellular

ComponentTransmembrane transportTranscription

factor bidingKinase

activityGamma-secretase complexDendritic

rootsRegulatory

protein complexes把GO當作圖GO的結構可以用圖的項（terms）來描述，每個GOterm代表一個節點，而terms之間的關系用節點間的邊來表示。GO

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

有2個父節點:organelle

（細胞器）以及cytoplasm

（細胞質）;而organelle

有2個子節點:mitochondrion,以及organelle

membrane又比如：Part

ofIs

aGO

terms之間的關系is

a

(is

a

subtypeof)part

ofhas

partRegulatesnegatively

regulates

and

positively

regulates.GO功能之間的關系可以利用AmiGO

and

QuickGO

來查看。is

a

和part

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

a，否則，只有其中一部分是屬于父節點的，則part

of。三個本體中（分子功能、細胞組分和生物過程）不會出現isa關系 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

關系為GO結構的基礎如果說AisaB，我們說A是B的亞類型.比如“mitoticcellcycle（有絲分裂細胞周期）”

is

a

“cellcycle”，或者“lyase

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

關系包含兩種，positively

regulates

和negatively regulates。haspart：是partof的互補邏輯，從父節點的角度來說部分—整體 的關系。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（胞內細胞器）”， 而“intracellular

organelle”is

an

“organelle”，因此

mitochondrion

is

an

organelle.如何推斷GO

term之間的關系is

a

&part

of

→

part

ofif

A

is

a

B,

and

B

is

part

of

C,A

is

part

of

C.（如果關系的順序相反，結果也是一樣的）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關于part

of

和is

a

關系的邏輯推理，與中間的is

a

和partof

關系 的數目無關。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

（關系順序相反，結果一樣）比如:

“precatalytic

spliceosome

（預

化剪接體）”

has

part “snRNP

U5”，而

“snRNPU5”

is

a

“small

nuclear ribonucleoprotein

complex

（小核核糖核蛋白復合體）”，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.互補減數分裂重組的激活減數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.（調換順序，結果一樣）“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 調節）”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

→

???凋亡誘導過程中蛋白質插入線粒體膜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填充的標識符(oftencalled

the term

accession

or

term

accession

number)如GO:0005125

或GO:0060092.ID

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

ID可以追溯誰添加的。Ontology

更新由GOC

ontology

團隊和請求更新的科學家完成。大 部分請求來自GO功能注釋的科學家（只是影響少數GO

terms）， 而特定生物領域中研究功能域的專家可能影響本體中包含很多GO terms和關系的整個分支。GOC邀請研究者和計算機科學家提交更新本體中GOterms和其之 間關系的請求。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

的注釋結果，將所有的GO注釋歸類到指定的數個GO

功能分類上。AmiGOQuickGOGO

term查詢GOIDGO

term名字GO

term描述對應基因的注釋條目（所有物種）該GO

term的同義詞語GO

term之間的關系子節點（GO）由UniProt-GOA提供的認為利用IEA方法獲得的錯誤注釋列表與該GO共同出現的GO

term同時出現的次數比較的GO

term出現的次數概率比概率相似度比該GO信息更改的日志518個對應基因的注釋條目（涉及所有物種）序列ID基因名該基因與該GO的關系注釋該條關系的參考信息物種ID注釋該條關系的組織提供518個注釋條目的統計信息證據參考信息物種注釋的組織或機構GO對應的類別查詢基因的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

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DNA

daiJJaoe

stimulus

cellular

renpDnse

to

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danJaoe

stimulus

Call

lar

ren0Dnse

to

UVcallclar

resgnnse

to

afiinnmycin

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respDnse

to

drugc.°.IIuIar

respDnse

to

gamma

radiatinn

cellular

respDnse

to

glucose

star\’atinn

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resPDnse

to

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?

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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據庫。是了解高級功能和生物系統（如細胞、生物和生態系統），從基因組到分子水平信息，尤其是大型分子數據集生成的基因組測序和其他高通量實驗技術的實用程序數據庫資源，由日本京都大學生物信息學中心的Kanehisa實驗室于1995年建立。是國際最常用的生物信息數據庫之一，以“理解生物系統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的分子構建塊（基因組信息）以及分子通路圖中被整合進相互作用、反應和關系網絡（系統信息）的化學物質（化學信息），而且還包含疾病和藥物信息（健康信息）KEGG系統信息基因組信息化學信息健康信息進一步可細分為18個主要的數據庫。可以通過不同的顏色編碼來區分。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個數字KEGGPATHWAY數據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、代表細胞和物種系統功能的關 系網絡：新陳代謝、遺傳信息加工、環境信息加工、細胞過程、 生物體系統、人類疾病、藥物開發。分子相互作用、反應和代表細胞和物種系統功能的關系網絡KEGG

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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生的.對于代謝通路圖中，每個盒子（或線）對應Knumber(KOidentifeir，基因),the

EC

number（酶）,and

the

R

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

maps

只對應它自己的內容，如基因或酶或反應.對于所有的代謝和非代謝通路，K標識符被認為是基因，可以將其轉化為物種的某個基因，用來產生物種特異的通路圖.map00010ko00010hsa00010“map”通路不標注顏色，“ko/ec/rn”通路標注為藍色，而物種特異的通路標注為綠色

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系類型。例如，可以查詢酶和底物之間的關系，也可以查詢某種酶的同源基因用層級關系結構的文件保存，（

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據集的生物意義1.通路模塊：代表在KEGG代謝通路圖中的復雜功能單元，例如

M00002(糖酵解，與三碳化合物相關的核心模塊)2.結構復合物：通常形成分子機械，例如M00072(寡糖轉移酶)3.功能集：基本單元的其他形式，例如M00360(氨酰基-tRNA合酶，原核生物)4.特征模塊：作為某種表型的標記，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

是手動建立的關于基因和蛋白（用K

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

files

由計算機自動 將K標識符轉化為物種對應的基因產生。The“br”hierarchy

file是化合物、反應、藥物、疾病和物種的功能 分類，用KEGG標識符，而不是K標識符。ko編號表示一個通路，這個通路是不分物種的，相當于所有物種 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稱KEGG

通路查詢EntryThumbnail

ImageNaweDescriptionObjectLegendhsa04110C

ell

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repic......ysis

hsa04010:

MAPK

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hsa04110:

CeII

cycle...4,6

CycH

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become......M01}

hsa05100:

Bacterialinvasion

of

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pithelial

cellshsa04512:

ECM-rece

ptorinteraction

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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