生物信息学第三讲基因功能富集分析

基因功能富集分析廖奇宁波大学医学院Gene

OntologyGene

Ontology(GO)提供目前可获得的基因或基因产物的功能，是一个可计算知识的最全面的资源，主要包含两大方面：Gene

Ontology生物功能（terms）之间的逻辑结构和它们之间的关系，表现为有向无环图（directedacyclic

graph）。GO注释基因产物(aprotein,non-coding

RNA,ormacromolecular

complex)对应的功能。GO注释涉及140000篇发表文献的实验发现，600000实验支持的GO注释条目。这些作为核心知识，用于其他超过600万来自不同物种的功能注释的推断。GO联合会(GOConsortium，GOC，/)也提供软件用于编辑和执行GO本体的逻辑推理、提供访问GO本体和注释的网上接口、提供基于GO知识支持生物医学研究的分析工具。各物种实验验证和非实验验证注释条目的数目GO类别GeneOntologyBiology

Process生物过程Molecular

Function分子功能Cellular

Component细胞组分GO类别分子功能：由基因产物所执行的分子水平上的活性单个大分子本身的活性或功能，通常通过与其他分子的物理相互作用来实现。主要包含两大功能：(1)生化活性，(2)作为一个大的系统或过程的组成部分细胞组分：基因产物实现功能所在的细胞结构上的定位当基因产物执行其功能时，所处的相对细胞组分和结构上的位置。主要有两种：（1）相对于细胞结构（例如，质膜的细胞质侧）或隔室（例如线粒体），（2）稳定的大分子复合物的一部分（例如核糖体）。与GO的其他方面不同，细胞组分不涉及过程，而是细胞解剖学。生物过程：由多个分子一起完成的生物程序、系统的过程。生物过程通常以其结果或终止状态来描述，例如，细胞分裂的生物学过 程导致从单个母细胞产生两个子细胞（分裂细胞）。生物过程是由一组特定基因产物（或大分子复合物）所执行的，通常被 高度调节，且在特定的时间点进行。Molecular

Function What

does

it

do?Biological

Process What

process

is

it

involved

in?Cellular

Component Where

does

it

act？早老素1蛋白在阿尔茨海默病中促进淀粉样前体蛋白的产生，导致淀粉样斑块的生成和神经纤维缠结的形成Beta-amyloid

formationCell

differentiationNeurotransmission regulationBrain

developmentPSEN1Biological

ProcessMolecular

FunctionCellular

ComponentTransmembrane transportTranscription

factor bidingKinase

activityGamma-secretase complexDendritic

rootsRegulatory

protein complexes把GO当作图GO的结构可以用图的项（terms）来描述，每个GOterm代表一个节点，而terms之间的关系用节点间的边来表示。GO

的结构是垂直而松散的子（child）节点相对于父（parent）节点的功能更加专一。父节点代表与图中根节点更近的节点，而子节点则更接近叶节点，因此，父节点所对应的描述更加宽泛，而子节点则更加专一，箭头代表关系的方向。点线表示推断的关系，而实线表示注释的关系。一个子节点可以有超过2个或以上的父节点。比如：mitochondrion

有2个父节点:organelle

（细胞器）以及cytoplasm

（细胞质）;而organelle

有2个子节点:mitochondrion,以及organelle

membrane又比如：Part

ofIs

aGO

terms之间的关系is

a

(is

a

subtypeof)part

ofhas

partRegulatesnegatively

regulates

and

positively

regulates.GO功能之间的关系可以利用AmiGO

and

QuickGO

来查看。is

a

和part

of表示子节点所描述的功能、细胞组分或过程从始至终都是属于父节点的， 为is

a，否则，只有其中一部分是属于父节点的，则part

of。三个本体中（分子功能、细胞组分和生物过程）不会出现isa关系 的交叉，而part_of

和regulates

则在不同的GO本体中会有交叉。比如，分子功能‘cyclin-dependent

protein

kinase

activity（细胞周期蛋白依 赖性蛋白激酶活性）’是part_of

生物过程‘cell

cycle’。is

a

关系为GO结构的基础如果说AisaB，我们说A是B的亚类型.比如“mitoticcellcycle（有丝分裂细胞周期）”

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为例子，比如a

cat

is

amammal，但是Garfield

is

an

instance

of

cat，而不是a

subtype

of

cat。不过，如果我们说cat

is

a

mammal，那么every

instance

of

cat

is

amammal.regulates

关系包含两种，positively

regulates

和negatively regulates。haspart：是partof的互补逻辑，从父节点的角度来说部分—整体 的关系。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（胞内细胞器）”， 而“intracellular

organelle”is

an

“organelle”，因此

mitochondrion

is

an

organelle.如何推断GO

term之间的关系is

a

&part

of

→

part

ofif

A

is

a

B,

and

B

is

part

of

C,A

is

part

of

C.（如果关系的顺序相反，结果也是一样的）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关于part

of

和is

a

关系的逻辑推理，与中间的is

a

和partof

关系 的数目无关。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

（线粒体膜）”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

（剪接体复合体）”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

（关系顺序相反，结果一样）比如:

“precatalytic

spliceosome

（预

化剪接体）”

has

part “snRNP

U5”，而

“snRNPU5”

is

a

“small

nuclear ribonucleoprotein

complex

（小核核糖核蛋白复合体）”，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依赖性激活剪接

体）”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.互补减数分裂重组的激活减数分裂重组检查点注意：如果X

注释为regulates

glycolysis的过程，不能推断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.（调换顺序，结果一样）“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（有丝分裂纺锤体组成的 调节）”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

→

???凋亡诱导过程中蛋白质插入线粒体膜regulation

of

anti—R

+—8B

—9-••••

•regulation

ofapoptosisis

a∘

...part

of

∘

...regulates

∘

...positively

regulates

∘

...negatively

regulates

∘

...has

part

∘

...GO

ID命名每个GO

term有一个名字：如mitochondrion,glucose

transport, amino

acid

binding。GOID为前缀为GO:，后面加七位0填充的标识符(oftencalled

the term

accession

or

term

accession

number)如GO:0005125

或GO:0060092.ID

的数字部分与这个term所处位置或意义无关。通常GOID的某一范围被 指定给每个本体的编辑或者编辑团队，因此，GO

ID可以追溯谁添加的。Ontology

更新由GOC

ontology

团队和请求更新的科学家完成。大 部分请求来自GO功能注释的科学家（只是影响少数GO

terms）， 而特定生物领域中研究功能域的专家可能影响本体中包含很多GO terms和关系的整个分支。GOC邀请研究者和计算机科学家提交更新本体中GOterms和其之 间关系的请求。GO的更新GO的基因注释可信等级来自/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:关于GO的缩减版本，间单地讲，为简化的Gene本体、简化GO

的注释结果，将所有的GO注释归类到指定的数个GO

功能分类上。AmiGOQuickGOGO

term查询GOIDGO

term名字GO

term描述对应基因的注释条目（所有物种）该GO

term的同义词语GO

term之间的关系子节点（GO）由UniProt-GOA提供的认为利用IEA方法获得的错误注释列表与该GO共同出现的GO

term同时出现的次数比较的GO

term出现的次数概率比概率相似度比该GO信息更改的日志518个对应基因的注释条目（涉及所有物种）序列ID基因名该基因与该GO的关系注释该条关系的参考信息物种ID注释该条关系的组织提供518个注释条目的统计信息证据参考信息物种注释的组织或机构GO对应的类别查询基因的GO注释信息NCBI

Entrez

Gene

（所有物种）GeneCards

（物种人）NCBI

Entrez

Gene的结果ProcessDNAdamage

response.

s

gnat

transduction

b\'

p53

class

mediator

DNA

damage

response,

signal

transduction

by

p53

class

mediatorDNS

damage

response,

signal

transduction

b}'

pñ3

class

mediator

resulting

in

c.°.II

r}'ce

arrest

DNA

damage

response,

signal

transduction

b\'

Pñ3

class

mediator

resulting

in

call

cycle

arrestDNA

damaga

response.

signaltransduction

by

pñ3

class

mediator

resulting

in

transrrintion

ofP21

class

mediator

DNA

damaga

response,

signaltransduction

b}'

pñ3

class

mediator

resulting

in

transrrintion

of

p21

class

mediator

DNAstrand

renaturatinnER

n\'arInad

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trannr:rintionaI

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protein

signal

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r*pair

cell

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gc=Il

cycle

arrest

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complexIDA1505387BGO:0005730nucleolusIDA12080348GO:0005737cytoplasmIEA,IMP16479015GO:0005736mitochondrionIDA,IEA12807443“KEGGKEGG（京都基因与基因组百科全书），是基因组破译方面的数据库。是了解高级功能和生物系统（如细胞、生物和生态系统），从基因组到分子水平信息，尤其是大型分子数据集生成的基因组测序和其他高通量实验技术的实用程序数据库资源，由日本京都大学生物信息学中心的Kanehisa实验室于1995年建立。是国际最常用的生物信息数据库之一，以“理解生物系统的高级功能和实用程序资源库”著称。https://www.kegg.jp/来自https://paintomics.readthedocs.io/en/latest/1_kegg/主要包含基因和蛋白质的分子构建块（基因组信息）以及分子通路图中被整合进相互作用、反应和关系网络（系统信息）的化学物质（化学信息），而且还包含疾病和药物信息（健康信息）KEGG系统信息基因组信息化学信息健康信息进一步可细分为18个主要的数据库。可以通过不同的颜色编码来区分。CategoryDatabaseContentColorSystemsKEGG

PATHWAYKEGG

pathway

mapsinformationKEGG

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hierarchies

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MODULEKEGG

modulesGenomicKEGG

ORTHOLOGY

(KO)Functional

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organisms

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GENESGenes

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SSDBGENES

sequence

similarityChemicalKEGG

COMPOUNDSmall

moleculesinformationKEGG

GLYCANGlycansKEGG

REACTIONBiochemical

reactionsKEGG

RCLASSReaction

classKEGG

ENZYMEEnzyme

nomenclatureHealthKEGG

NETWORKDisease-related

network

elementsinformationKEGG

VARIANTHuman

gene

variantsKEGG

DISEASEHuman

diseasesKEGG

DRUGDrugsKEGG

DGROUPDrug

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ENVIRONHealth-related

substancesDatabaseObjectPrefixExamplepathwayKEGG

pathway

mapmap,

ko<org>map00010map00010ec,

rnhsa04930hsa04930briteBRITE

functional

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jp<org>br:08303br08303kobr:01002ko01002moduleKEGG

moduleM<org>_MM00010M00010koKO

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orthologKK04527genomeKEGG

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proteinhsa:3643vgvg:155971agag:CAA76703compoundSmall

moleculeCC00031glycanGlycanGG00109reactionReactionRR00259rclassReaction

classRCRC00046enzymeEnzymeec:networkNetwork

elementsNN00002variantHuman

gene

variantshsa_var:25v1diseaseHuman

diseaseHH00004drugDrugDD01441dgroupDrug

groupDGDG00710environHealth-related

substanceEE00048+5个数字KEGGPATHWAY数据库是一个手工画的代谢通路的集合，包含以下 几方面的分子间相互作用、反应、代表细胞和物种系统功能的关 系网络：新陈代谢、遗传信息加工、环境信息加工、细胞过程、 生物体系统、人类疾病、药物开发。分子相互作用、反应和代表细胞和物种系统功能的关系网络KEGG

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

PATHWAY–由2-4字母的前缀+5个数字代表，前缀意义如下:map-Reference

pathway(map)：参考通路图ko-Reference

pathway(KO)：基因ec-Reference

pathway(EC)：酶rn-Reference

pathway(Reaction)：反应org-Organism-specificpathway

map

：物种特异的通路图仅仅第一种参考通路(referencepathway)图是手动绘制的，其他的通路图都是通过计算产生的.对于代谢通路图中，每个盒子（或线）对应Knumber(KOidentifeir，基因),the

EC

number（酶）,and

the

R

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

maps

只对应它自己的内容，如基因或酶或反应.对于所有的代谢和非代谢通路，K标识符被认为是基因，可以将其转化为物种的某个基因，用来产生物种特异的通路图.map00010ko00010hsa00010“map”通路不标注颜色，“ko/ec/rn”通路标注为蓝色，而物种特异的通路标注为绿色

在完整的整个代谢通路图中，“map”pathways被完全着色，而“ko/ec/rn”pathways和organism-specific

pathways

如果没有着色，则表示缺乏对应的对象。图的符号含义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层级分类表包含了许多不同的关系类型。例如，可以查询酶和底物之间的关系，也可以查询某种酶的同源基因用层级关系结构的文件保存，（

htextfile），每行第一个字符为“A”,“B”,“C”,等，表示层级等级，低级别的内容可能包含很多tab空格.KEGG

MODULE

：人工定义的功能单元集合，用于解释基因的高通量数据集的生物意义1.通路模块：代表在KEGG代谢通路图中的复杂功能单元，例如

M00002(糖酵解，与三碳化合物相关的核心模块)2.结构复合物：通常形成分子机械，例如M00072(寡糖转移酶)3.功能集：基本单元的其他形式，例如M00360(氨酰基-tRNA合酶，原核生物)4.特征模块：作为某种表型的标记，例如M00363(肠出血性大肠杆菌致病性特征，志贺毒素)每个BRITE

hierarchy

文件用2-4

letter

code

和5

digit

number

标识， 前缀意思如下:br

-

Reference

hierarchyjp

-

Reference

hierarchy

in

Japaneseko

-

Reference

hierarchy

(KO)org

-

Organism-specifichierarchy“ko”hierarchy

file

是手动建立的关于基因和蛋白（用K

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

files

由计算机自动 将K标识符转化为物种对应的基因产生。The“br”hierarchy

file是化合物、反应、药物、疾病和物种的功能 分类，用KEGG标识符，而不是K标识符。ko编号表示一个通路，这个通路是不分物种的，相当于所有物种 的这一通路的并集。K编号表示一个基因，是ko通路中的基本单位，某一K编号代表的 不是某一具体物种的基因，而是所有物种的某一同源基因的统称KEGG

通路查询EntryThumbnail

ImageNaweDescriptionObjectLegendhsa04110C

ell

cycle

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tic

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I

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progression

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d

throug

h

are

producibe

seque

nœ

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.

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tBacerial

invasion

ofepithelial

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can

invade

phagocyticand

no

n—phapocytic

cells

andcolonize

them

intracellularly,the

n

become......M01}

hsa05100:

Bacterialinvasion

of

e

pithelial

cellshsa04512:

ECM-rece

ptorinteraction

nsa04810:

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OFEPITHELIAL

CELLS

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n

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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