VisualSNP 20061128

50 %
50 %
Information about VisualSNP 20061128
Education

Published on January 17, 2008

Author: Sibilla

Source: authorstream.com

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

Add a comment

Related presentations