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實用生物資訊研習課程
2008/04/09 - FastSNP
生物醫學資訊所 博士班
邱振傑
生物資訊校內推廣
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主辦單位：生物醫學資訊研究所
推廣宗旨：有效解決生物資訊問題、實用工具推廣
預期目標：真正協助各領域的研究
互動方式：
– 實用生物資訊研習課程 – 面對面推廣
– 「生物資訊論壇」（免註冊帳號）- 線上互動
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What is FastSNP?
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An website – http://fastsnp.ibms.sinica.edu.tw
IIS & IBMS, Academia Sinica
進階生物資訊核心設施, 基因體國家型計畫
Nucleic Acids Research 2006 34(Web Server
issue):W635-W641; doi:10.1093/nar/gkl236
Bioinformatics for Geneticists: A Bioinformatics
Primer for the Analysis of Genetic Data (2nd edition)
Website traffic
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Advanced Bioinformatics Core (ABC)
進階生物資訊核心設施
Genome
related info
許鈞南
Hsu, Chun-Nan
資訊科學技術
Information
Technology
IT
比較生物資訊
Comparative
Bioinformatics
張傳雄
Chang, Chuan-Hsiung
CB
李國彬
Li, Kuo-Bin
FB
功能生物資訊
Functional
Bioinformatics
楊永正
Yang, Ueng-Cheng
GS
基因體研究統計
Genomic
Statistics
陳珍信 Chen, Chen-Hsin
陳君厚 Chen, Chun-houh
Preventive &
personal medicine
http://abc.binfo.org.tw/
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Website
traffic
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Purpose of FastSNP
Millions of SNPs deposited in public SNP databases,
only a very small proportion may contribute to
disease phenotypes
• to approach functional variation in a disease
in association studies.
• to help selecting SNPs more efficiently
• to generate a Completely Function Report
for a SNP
 “A Functional Analysis and Selection Tool
for SNP".
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Strategy for SNP selection
• Specific disease or phenotype
• Select candidate genes, regions (PubMed, OMIM…etc)
• Retrieve SNP data from public domain databases
(dbSNP, Ensembl…etc)
• SNP selection work!
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It depends on your criterion
To get SNP list, Flanking sequence
Primer design for genotyping
Basic information of selected SNPs
“SNP functional effects” for example
• Many on-line tools can do different analysis
• But hard to integrate all results from out source
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Query Module
Function Analysis Module
ESEfinder
Seq.
EnsemblMart
RESCUE-ESE
HUGO Aliases
FAS-ESS
Gene
NCBI Gene Symbol
coding
PolyPhen
SNP set
?
TFSearch
non-coding
Ensembl Protein Domain
dbSNP
SNP
SNP Seq.
SNP basic Info.
SNP prediction Info.
SNP functional effects
Function Report Module
Prioritization Module
UCSC Seq. Check
Classification
Ranking
SNP
Function
Report
Link out query
HapMap Haplotype
SwissProt’s Feature
Generate SNP function report
GenBank Protein Domain
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Real-Time SNP Data Analysis
Gene Symbol
Candidate Gene Approach
SNP rsID
Single SNP (batch)
Chromosome
SNP Search
Novel SNP
ESEfinder
RESCUE-ESE
Ensembl
Agent Starter
dbSNP
TFSEARCH
PolyPhen
Swiss-prot
Function
Report
NCBI GenBank
Prioritization
Decision tree
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Functional effect for coding SNP
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Functional effect for non-coding
SNP
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Decision tree
SNP
Coding?
No
5' upstreaam,
5' UTR, 3'
UTR?
No
Intronic?
Yes
TF binfing
site?
No
Downstream with
no known function
Yes
No
TF binding
site?
Risk = 0
Upstream with
no known function
Yes
Risk = 0
No
Splicing
Site?
No
Risk = 0
Intronic with no known function
Yes
Yes
Risk = 1~ 3
Risk = 1 ~ 2
Risk = 3 ~ 4
Promoter / regulatory region
Intronic enhancer
Splicing site
Yes
Non-sense?
No
Nonsynonymous
?
Splicing
regulation?
No
No
Risk = 1
Sense / synonymous
Yes
Yes
Yes
ESE Motif
diminish?
Affect protein
structure?
Yes
Risk = 5
No
Risk = 2 ~ 3
No
Yes
Mis-sense
(leading to conservative change)
Protein
domain
abolished/
No
Risk = 3 ~ 4
Yes
Non-sense
Mis-sense
(leading to non-conservative change)
Risk = 2 ~ 3
Splicing regulation
Risk = 3 ~ 4
Splicing regulation
(protein domain abolished)
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FastSNP user guide
• http://fastsnp.ibms.sinica.edu.tw/userguide/
UserGuide.jsp
• A result example:
– http://fastsnp.ibms.sinica.edu.tw/pages/Prioritiz
eResult.jsp?taskid=TK14938&Submit=ENST000
00272895
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Result - SNP list
Click here to export SNP list to Excel format
Click here to get “Function Report”
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Function Report
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Click here to get detail information
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Hands on session
• 任意挑選Coding region與Non-coding region的SNP
各三個進行FastSNP分析。
– 取得SNP周圍的DNA序列
– 寫下這三個SNP分別被預測屬於產生哪種Functional
effects？
• 以一個您正在研究的疾病為例，輸入Candidate
gene，看看是否FastSNP能找到資料並進行分析？
• 如果我所輸入的Gene Symbol出現多筆
Transcription資訊，我該如何判斷選擇哪一個？
• 我分析完成的結果，要如何回去看呢？
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謝謝您的參與
關於本課程後續相關討論，
可上「生物資訊論壇」（免註冊）
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