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On the Selection of Tag SNPs for Capturing Human Leukocyte Antigen

Discover the methodology for selecting tag SNPs to efficiently capture HLA genes essential in transplantation. Reduce time and costs associated with traditional HLA typing using a systematic approach.

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On the Selection of Tag SNPs for Capturing Human Leukocyte Antigen

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  1. On the Selection of Tag SNPs for Capturing Human Leukocyte Antigen

  2. HLA Genes • HLA genes located on chromosome 6 • The genes’ expression is codominance • They have a great diversity • They encode cell-surface antigen-presenting proteins • They play an important role in immune system and transplantation

  3. SNPs and Haplotype

  4. Problem • Before transplantation, the donor and the acceptor must compare their HLA type • The traditional biological HLA typing is time-consuming and expensive • The method we use is much faster and cheaper • We want to find a small subset of the given SNPs called tag SNPs, which is able to capture the HLA genes

  5. Method • Stage1 • Set Cover • Stage2 • Prediction • Result

  6. Example of TagSNPs(Stage1) C C C C C A C A C A A A A A A A C A C A S1 S2 S3 S4 S5 S6 A A A A A T T T T T T, A C, C HLA-A-0301 HLA-A-0301 HLA-A-0301 HLA-A-0301 HLA-A-0301 HLA-A-0502 HLA-A-0502 HLA-A-0502 HLA-A-0502 HLA-A-0502 G1 G1 HLA-A0301 HLA-A0502 C C C C C C G G G C A T A T A C C A A A A A C C C C C C C C

  7. Method • Stage1 • Set Cover • Stage2 • Prediction • Result

  8. Set cover S1 S2 S3 S4 A T A T C G G C A A A A C C C T 0301 0405 0502 0704 • Every time select a SNP which cover the most pair • Until every pair is covered • then generate a set of tag SNPs S1 S2 S3 S4 0301 0301 0301 0405 0405 0502 0405 0502 0704 0502 0704 0704

  9. Method • Stage1 • Set Cover • Stage2 • Prediction • Result

  10. Example of TagSNPs(Stage2) C C C C C A C A C A A A A A A A C A C A S1 S2 S3 S4 S5 S6 A A A A A T T T T T T, A orC,C C, A orA,C HLA-A-0301 HLA-A-0301 HLA-A-0301 HLA-A-0301 HLA-A-0301 HLA-A-0502 HLA-A-0502 HLA-A-0502 HLA-A-0502 HLA-A-0502 HLA-A0301 HLA-A0502 C C C C C A A A A A C G G G C A T A T A C C A A A A A C C C T T T T T C C C C C

  11. Method • Stage1 • Set Cover • Stage2 • Prediction • Result

  12. Prediction Leave one out to test Delete appear one time allele type Observe the similarity between the testing data and training data If the answer we find has the same allele type with testing data then we say prediction is successful

  13. Prediction example S01S02 S03S04 S05 S06 … HLA-A-0301CA A TTC ... Stage1 HLA-A-0301C AAT TC ... HLA-A-0405 T T C C T C ... HLA-A-1701 T A A T A C ... Set Cover HLA-A-1920 C T C C T T ... HLA-A-4050 T A C C T T ... Stage2 HLA-A-5101 T A C C A T ... HLA-A-6050 T A A C T C ... HLA-A-7810 C T C T A T ... HLA-A-8801 T T A C A C ...

  14. Prediction example Score: Match:+1 Dismatch:+0 S10S26 S39S03 S08 S89 Test 0301CA A ATC HLA-A-0301C AAA TC HLA-A-0405 T T C C T C HLA-A-1701 T A A A A C HLA-A-1920 C T C C T T HLA-A-4050 T A C C T T HLA-A-5101 T A C C A T HLA-A-6050 T A A A T C HLA-A-7810 C T C C A T HLA-A-8801 T T A A A C

  15. Prediction example S01S02 S03S04 S05 S06 … HLA-A-0301CA A TTC ... Stage1 HLA-A-0301C AAT TC ... HLA-A-0405 T T C C T C ... HLA-A-1701 T A A T A C ... Set Cover HLA-A-1920 C T C C T T ... HLA-A-4050 T A C C T T ... Stage2 HLA-A-5101 T A C C A T ... HLA-A-6050 T A A C T C ... HLA-A-7810 C T C T A T ... HLA-A-8801 T T A C A C ...

  16. Flowchart • Entropy • Set Cover • Data Propose • Prediction • Result

  17. HLA Region

  18. HLA-A HLA-B HLA-C

  19. HLA-QA HLA-QB HLA-RB

  20. Reference • http://www.ncbi.nlm.nih.gov/ • http://www.hapmap.org/whatishapmap.html.en • http://www.imflammegn.org

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