On the Selection of Tag SNPs for Capturing
- Slides: 20
On the Selection of Tag SNPs for Capturing Human Leukocyte Antigen
HLA Genes n n n HLA genes located on chromosome 6 The genes’ expression is codominance They have a great diversity They encode cell-surface antigenpresenting proteins They play an important role in immune system and transplantation
SNPs and Haplotype
Problem n n 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
Method n n n Stage 1 Set Cover Stage 2 Prediction Result
Example of Tag. SNPs(Stage 1) S 1 S 2 S 3 S 4 S 5 S 6 HLA-A-0301 C A A A T A HLA-A-0301 C A C T A HLA-A-0301 C A A T A HLA-A-0301 C A C C G A 1 C T A HLA-A-0301 C A A A T A HLA-A-0502 C A C HLA-A-0502 G T C A C C HLA-A-0502 G A A C C C HLA-A-0502 G T A C C C HLA-A-0502 C A A C C C G 1 C T, A HLA-A 0301 C, C HLA-A 0502
Method n n n Stage 1 Set Cover Stage 2 Prediction Result
Set cover S 1 S 2 S 3 S 4 0301 A C 0405 T G A C 0502 A G A C 0704 T C A T S 1 0301 0405 0301 0502 n. Every time select a SNP which cover the most pair n. Until every pair is covered then generate a set of tag SNPs S 2 0301 0704 S 3 0405 0502 S 4 0405 0704 0502 0704
Method n n n Stage 1 Set Cover Stage 2 Prediction Result
Example of Tag. SNPs(Stage 2) S 1 S 2 S 3 HLA-A-0301 C A A HLA-A-0301 C HLA-A-0301 S 4 S 5 S 6 A T A C C T A C A A A T A HLA-A-0502 C A T C A C HLA-A-0502 G A A C T C A C HLA-A-0502 G T A C T C A C HLA-A-0502 C A A C T C A C T, A or C, C HLA-A 0301 C, A or A, C HLA-A 0502
Method n n n Stage 1 Set Cover Stage 2 Prediction Result
Prediction n n 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
Prediction example S 01 S 02 S 03 S 04 S 05 S 06 … 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 A T . . . HLA-A-8801 T T A C . . . Stage 1 Set Cover Stage 2
Score: Match: +1 Dismatch: +0 Prediction example S 10 S 26 S 39 S 03 S 08 S 89 Score 0301 C A A A T C 6 HLA-A-0301 C A A A T C 2 HLA-A-0405 T T C C T C HLA-A-1701 T A A C 3 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 1 HLA-A-6050 T A A A T C 2 HLA-A-7810 C T C C A T 2 HLA-A-8801 T T A A A C 2 Test 2 2
Prediction example S 01 S 02 S 03 S 04 S 05 S 06 … 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 A T . . . HLA-A-8801 T T A C . . . Stage 1 Set Cover Stage 2
Flowchart n n n Entropy Set Cover Data Propose Prediction Result
HLA Region
HLA-A HLA-B HLA-C
HLA-QA HLA-QB HLA-RB
Reference n n n http: //www. ncbi. nlm. nih. gov/ http: //www. hapmap. org/whatishapmap. ht ml. en http: //www. imflammegn. org
