生物信息学第四讲基因调节网络分析

基因调节网络分析廖

奇宁波大学医学院主要内容蛋白互作、转录因子调节关系数据库的介绍和使用非编码RNA调节网络数据库的介绍和使用基因网络图的展示、Cytoscape软件的介绍和使用蛋白蛋白相互作用STRINGMIPSBioGRIDIntActHPRDSTRING输入蛋白名、蛋白描述、基因名选择物种/名字序列多个蛋白名字多个蛋白序列显示物种信息蛋白家族（家族名、单个或多个蛋白名、序列等）网络节点、边颜色的意义Input

protein预测的相

互作用蛋白线的颜色、粗细、形状代表

不同意思，选择其中一种展示相互作用的来源预测相互作用的最低分值相互作用蛋白的个数图形类型图显示参数基因功能富集网络基本信息基因功能富集计算富集功能的背景输出结果相互作用关系MIPSMIPS收集由专业审核者从文献中手动核对的高质量的哺乳动物蛋白蛋白相互作用。只选取单通量实验验证的数据，因为更可靠。http://mips.gsf.de/proj/ppi/蛋白1的信息蛋白2的信息相互作用的信息BioGRID目前版本：3.4.163，搜索了65590篇发表的文献，收录了来自主要模式物种的1591402个蛋白和遗传相互作用，27785个化学反应和39028个转录后修饰/…

…目前收录的统计信息1）基因名、基因ID、关键词2）Pubmed

ID3）3个字符+*，如MYC*多个关键词搜索,

AND,

ORSH2

OR

Domainprotein

AND

kinase

ANDadapter

(+protein

+kinase+adapter)c.

+protein

+kinase–yeastd.+“proteinkinasedomain”

-“SH2Domain”e.+(proteinkinasedomain)

+(sh2domain)数据下载相互作用的分子信息富集的GO功能相互作用的信息化合物信息组蛋白修饰位点未知特定位点的关联的蛋白网络展示IntAct比如输入MYC基因相互作用自定义显示条目下载相互作用分子不同种类的分子HPRD/查询浏览比对输入MYC功能表达定位相互作用序列比对转录因子调节关系TRRUSTCistromeTRRUST/trrustHuman:

800

TFs

8,444

TF-target

regulatory

relationshipsMouse:

828

TFs

6,552

TF-target

regulatory来源于11,237

pubmed

文献。输入一个基因名，如BRCA1、MYC等输入基因列表，用逗号分隔调节的靶基因上游调节的TFs共有靶基因的TF查询高通量数据检测的转录因子靶基因数据库（高通量数据来源，具有一定的可信度）/Cistrome/Cistrome_Project.htmlCistrome转录因子靶基因输入关键词，如转录因子名字选择物种选择细胞系选择转录因子搜索人CEPBP在不同生物过程下的靶基因选择其中1个，得到如下基本信息GEO数据库的ID生物过程或细胞系信息ChIP-seq数据基本信息，可忽略靶基因点击putative

targets下载选择排序靠前的靶基因较为可信，若想进一步提高可靠性：多个同个转录因子不同细胞系（或相同细胞系）的靶基因取交集与共表达的蛋白编码基因取交集转录因子在癌症中的靶基因转录因子选择转录因子和癌症类型miRNA

target

database（实验验证）miRTarBaseTarBasemiRTarBase靶基因Tarbasehttp://carolina.imis.athena-

innovation.gr/diana_tools/web/index.php?r=tarbasev8%2Findex比如，输入hsa-let-7b-3p靶基因miRNA

target

database（预测）TargetScanmiRDBmiRcodeTargetScan/vert_72/比如输入MYC调节的miRNAsmiRDB由软件MirTarget预测而来的结果。MirTarget基于高通量检测的miIRNA-靶基因关系，提取相关特征，构建机器学习方法，从而获得预测模型。包含5个物种，

human,

mouse,

rat,

dog

和

chicken.比如输入MYC/index.html查询的结果miRNA信息miRcode输入MYC或者ENSG00000136997.9/index.phpSearch

MYCSearch

miR-155Search

linc00472非编码RNA综合数据库starBasemiRNA-ncRNA,miRNA-mRNA,ncRNA-RNA,RBP-

ncRNA

and

RBP-mRNA

interactions1.1millionmiRNA-ncRNA,

2.5millionmiRNA-mRNA,0.9millionRBP-ncRNAand1.1

millionRBP-mRNA

interactionsgeneexpressiondataof32typesofcancerswhich

arederivedfrom10,159RNA-seqand9,925miRNA-

seqdata/点击更换参数后，点击√，再点击Quick

Search更换参数对特定列进行筛查ceRNA调节关系RNA结合蛋白相互作用预测catPARID/page/catrapid_group/update_submission/143562/31bb002528选择物种输入蛋白序列基于蛋白序列进行预测基于RNA序列进行预测/update_submission/143563/73bf419b9e调节网络综合数据库RegNetworkTF→TFTF→geneTF→miRNAmiRNA→TFmiRNA→gene/DATABASEDESCRIPTIONSPECIESWEBSITEBioGridBioGRID

is

an

online

interaction

repository

with

data

compiled

through

comprehensive

curationeffortsMouse/EnsemblEnsembl

is

to

provide

a

centralized

resource

for

geneticists,

molecular

biologists

and

other

researchers

studying

the

genomes

of

our

own

species

and

other

vertebrates

and

model

organismsHuman

and

mouseHPRDHPRD

is

a

curated

human

protein-protein

interaction

databaseHumanIntActIntAct

is

a

database

system

of

molecular

interaction

data.

All

interactions

are

derived

from

literature

curation

or

direct

user

submissionsMousehttp://www.ebi.ac.uk/intact/KEGGKEGG

is

a

widely

used

pathway

database

resource

for

understanding

high-level

linkage

functionsand

utilitiesof

biological

systemHuman

and

mousehttp://www.genome.jp/kegg/MicroTDIANA-microT

is

a

combined

computational-experimental

approach

predicts

mouse

microRNAtargetsHuman

and

mousehttp://www.microrna.gr/microTmiRandamiRanda

is

a

miRNA

target

prediction

method

based

on

dynamic

programming

algorithmHuman

and

mousemiRBasemiRBase

database

is

a

searchable

database

of

published

miRNA

sequences

and

annotationHuman

and

mouse/miRecordsmiRecords

is

a

resource

for

animal

miRNA-target

interactions.

The

validated

targets

component

is

used,

which

is

a

large,

high-quality

database

of

experimentally

validated

miRNAtargetsHuman

and

mousehttp://miR/miRecordsmiRTarBasemiRTarBase

is

a

database

which

curates

experimentally

validated

microRNA-targetinteractionsHuman

and

mousehttp://miRTarB.tw/PicTarPicTar

is

a

computational

method

for

identifying

common

targets

of

microRNAsHuman

and

mousehttp://pictar.mdc-berlin.de/STRINGSTRING

is

a

database

of

known

and

predicted

protein

interactionsMouseTarbaseTarbase

collectes

available

miRNA

targets

derived

from

all

contemporary

experimental

techniques(gene

specific

and

high-throughput)Human

and

mousehttp://www.microrna.gr/tarbaseTargetScanTargetScan

is

an

algorithm

to

predict

biological

targets

of

miRNAs

by

searching

for

the

presence

of

conserved

8mer

and

7mer

sites

that

match

the

seed

region

of

each

miRNAHuman

and

mouse/TransmiRTransmiR

is

a

transcription

factor-microRNA

regulation

databaseHuman

and

mouse51/hmdd/mirna/tf/TREDTranscriptional

Regulatory

Element

Database

(TRED)

is

an

integrated

repository

repository

for

both

cis-

and

trans-

regulatory

elements

in

mammals.

It

contains

the