VisualSNP 20061128

Download
Share  Add to  Flag Embed
Uploaded from authorPOINTLite
Views:
 
Category: Education
     
 
License:   All Rights Reserved

Presentation Description

No description available.

Comments

 

By: Lorna.lih (25 month(s) ago)

Great presentation. I would be very grateful if I could have a copy of it. Thanks. Lorna Li

 

By: DrHealth (45 month(s) ago)

Great presentation. I would like permission to have a copy of it. You will be credited properly. Thanks, Bill Simons (William J Simons, MD, Asheville, NC)

Presentation Transcript

VisualSNP v1.2 Robust Functional SNP Prioritization Tool: 

VisualSNP v1.2 Robust Functional SNP Prioritization Tool 劉傳崑 chuankun@ibms.sinica.edu.tw Biomedical IT Core Institute of Biomedical Sciences Academia Sinica 2006/11/28

Outline: 

Outline Introduction System Interface Method Risk type and Risk level Live Demo Conclusion

Introduction: 

Single Nucleotide Polymorphism (SNP) Introduction A point mutation ? Within a population, one will refer to SNPs with a minor allele frequency of ≧ 1% (or 0.5% etc.).

Introduction: 

Variation Class: SNP: single nucleotide polymorphism 9,636,322 80.82% DIP: deletion/insertion polymorphism 2,202,926 18.48% MIXED: 51,775 0.43% MNP: 16,329 0.14% NAMED: 9,815 0.08% STR: 5,096 0.04% NO VARIATON: 424 0.004% HETEROZYGOUS: 4 0.00003% Introduction Updated 2006/11/15 NCBI dbSNP 126

Introduction: 

Introduction ATG TAA GT AG Intron Exon1 Exon2 Promoter downstream upstream 5' 3' SNP Function: Nonsynonymous Synonymous Example:

Introduction: 

Introduction Cartegni, L., S. L. Chew, et al. (2002). Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 3(4): 285-98. Exon Splicing Enhancer (ESE) Exon Splicing Silencer (ESS) RS domain RNA Recognition Motifs (RRM)

Introduction: 

Introduction Homo sapiens Updated 2006/11/15 NCBI Build 36.2 NCBI dbSNP 126

Introduction: 

Check the location and the function of the SNP Introduction The aim of VisualSNP is to prioritize the risk level of all SNP related to human genes based on the phenotypic risk. RESCUE-ESE Web Server FAS-ESS web server Check any protein domain or motif contain SNP Check protein structure affection by SNP Check any exon splicing enhancer cover SNP Check any exon splicing silencer cover SNP Extract transcripts information and compare to data from NCBI Check any stop codon generate by SNP

System interface: 

System interface GenePipe http://genepipe.ngc.sinica.edu.tw

System interface: 

System interface GenePipe http://genepipe.ngc.sinica.edu.tw VisualSNP http://genepipe.ngc.sinica.edu.tw/visualsnp

System interface: 

System interface Gene Official Symbol

System interface: 

System interface Gene Official Symbol Gene Alias

System interface: 

System interface Single SNP rsID

System interface: 

System interface

System interface: 

System interface

System interface: 

System interface

Processing: 

Processing

Processing: 

2. Invalid dbSNP rsID or gene name 4. The gene is not found 5. Find more than one gene 6. The gene has no transcript 7. No SNPs in the coding region 3. SNPs number is over the upper limit 100 Processing

Result page: 

a. Summary Result page

Result page: 

b. Global View Result page

Result page: 

c. Transcript View Result page

Result page: 

d. SNP View 3. Provide 200 bps flanking seq 4. Primer design (PrimerZ) Result page 2. Descriptions and source links

Result page: 

d. SNP View 5. Display the result of each SNPs 6. Show detailed info of each steps 7. Link to original websites Result page

Result page: 

e. Export Result Result page

Method: 

Method

Check the location and the function of the SNP: 

Check the location and the function of the SNP

Check any stop codon generate by SNP: 

Check any stop codon generate by SNP

Check any stop codon generate by SNP: 

Check any stop codon generate by SNP

Check protein structure affection by SNP: 

Check protein structure affection by SNP

Check protein structure affection by SNP: 

62241015 K301H NCBI Protein GI Original AA + Position + New AA Searches for similar sequences Chooses sequences that may have similar function Makes a multiple alignment of the chosen sequences Calculates normalized probabilities for all possible substitutions at each position from the alignment http://blocks.fhcrc.org/sift/SIFT.html Pauline C. Ng and Steven Henikoff (2003) SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res., 31, 3812-3814. Check protein structure affection by SNP

Check protein structure affection by SNP: 

Check protein structure affection by SNP

Check any exon splicing enhancer / silencer cover SNP: 

Check any exon splicing enhancer / silencer cover SNP

Check any exon splicing enhancer / silencer cover SNP: 

RESCUE-ESE Web Server 238 hexamers as candidate ESEs Fairbrother WG, Yeh RF, Sharp PA, Burge CB. Predictive identification of exonic splicing enhancers in human genes. Science. 2002 Aug 9;297(5583):1007-13. http://genes.mit.edu/burgelab/rescue-ese/ cctggTgaagg Check any exon splicing enhancer / silencer cover SNP

Check any exon splicing enhancer / silencer cover SNP: 

FAS-ESS web server 176 hexamers as candidate ESSs Wang, Z., Rolish, M. E., Yeo, G., Tung, V., Mawson, M. and Burge, C. B. (2004). Systematic identification and analysis of exonic splicing silencers. Cell 119, 831-845. http://genes.mit.edu/fas-ess/ agtgtTtggac Check any exon splicing enhancer / silencer cover SNP

Check any protein domain or motif contain SNP: 

Check any protein domain or motif contain SNP

Check any protein domain or motif contain SNP: 

Conserved Domains Entrez Protein Check any protein domain or motif contain SNP

Risk type and Risk level: 

7 Risk Type 4 Risk Level (1) Non-sense (2) Mis-sense (Non-conservative change) (3) Mis-sense (Protein domain abolished) (4) Mis-sense (conservative change) (5) Exon splicing regulation (Protein domain abolished) (6) Exon splicing regulation (7) Sense Risk type and Risk level

Slide38: 

Non-sense rs11555436

Slide39: 

Mis-sense (Non-conservative change) rs11555431

Slide40: 

Mis-sense (Protein domain abolished) rs11555433

Slide41: 

Mis-sense (conservative change) rs28931576

Slide42: 

Exon splicing regulation (Protein domain abolished) rs2230508

Slide43: 

Exon splicing regulation rs17846825

Slide44: 

Sense rs1130233

Live Demo: 

Live Demo Query by gene name APOE, apoprotein, BRCA1, RP11-493K23.3 Query by single SNP rs4988111, rs12269642, rs2771 Batch SNP query Case for exceptions http://genepipe.ngc.sinica.edu.tw/visualsnp

Conclusion: 

Prioritize the risk level of SNPs according to phenotypic data from five website Conclusion Extract data from website immediately without database Provide a visualized interface to browse the risk level of SNPs Provide links to go back to the source page Export all result data as a CSV file for downloading

Slide47: 

陳衍豪 姚文萱博士 林依蓉 蔡明芳 鄭煜璋

Thanks for your listening!: 

Thanks for your listening! http://genepipe.ngc.sinica.edu.tw/visualsnp VisualSNP

Examples: 

Gene Name: APOE BRCA1 ATM AKT1 LPL ORC4L ADSL CYP2C9 SNP rsID: rs328 rs12269642 rs11083750 rs769452 rs28931576 rs1060788 rs11542033 rs11542038 rs3218672 Examples