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) HLA-A-0301 HLA-A-0502 CCCCCCCCCC CGGGCCGGGC ATATAATATA CCAAACCAAA AACCCAACCC CCCCCCCCCC CCCCCCCCCC AAAAAAAAAA ACACAACACA ACACAACACA TTTTTTTTTT AAAAAAAAAA G1G1 S1 S2 S3 S4 S5 S6 G1 T, A HLA-A 0301 C, C HLA-A 0502

7. Method Stage1 Set Cover Stage2 Prediction Result

8. Set cover 0301 0405 0502 0704 S1S2S3S4 0301 0301 0301 0405 0405 0502 0405 0502 0704 0502 0704 0704 S1 S2 S3 S4 Every time select a SNP which cover the most pair Until every pair is covered then generate a set of tag SNPs ATATATAT CGGCCGGC AAAAAAAA CCCTCCCT

9. Method Stage1 Set Cover Stage2 Prediction Result

10. Example of TagSNPs(Stage2) HLA-A-0301 HLA-A-0502 CCCCCCCCCC CGGGCCGGGC ATATAATATA CCAAACCAAA AACCCAACCC TTTTTTTTTT AAAAAAAAAA AAAAAAAAAA ACACAACACA ACACAACACA TTTTTTTTTT AAAAAAAAAA S1 S2 S3 S4 S5 S6 CCCCCCCCCC CCCCCCCCCC T, A or C,C HLA-A 0301 C, A or A,C HLA-A 0502

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 S01 S02 S03 S04 S05 S06 … HLA-A-0301 C A A T T C... HLA-A-0405 T T C C T C... HLA-A-1701 T A A T 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 C T C... HLA-A-7810 C T C T A T... HLA-A-8801 T T A C A C... Stage1 Set Cover Stage2

14. Prediction example S10 S26 S39 S03 S08 S89 Test 0301 C A A A T C HLA-A-0301 C A A A T C 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 Score: Match:+1 Dismatch:+0 Score 6 2 3 2 2 1 2 2 2

15. Prediction example S01 S02 S03 S04 S05 S06 … HLA-A-0301 C A A T T C... HLA-A-0405 T T C C T C... HLA-A-1701 T A A T 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 C T C... HLA-A-7810 C T C T A T... HLA-A-8801 T T A C A C... Stage1 Set Cover Stage2

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.ht ml.en http://www.imflammegn.org