On the Selection of Tag SNPs for
Capturing Human Leukocyte
Antigen
HLA Genes
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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
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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
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Stage1
Set Cover
Stage2
Prediction
Result
Example of TagSNPs(Stage1)
S1
S2
S3
S4
S5
S6
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
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
G1
C
T, A
HLA-A
0301
C, C
HLA-A
0502
Method
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Stage1
Set Cover
Stage2
Prediction
Result
Set cover
0301
S1
A
S2
C
S3
A
S4
C
0405
T
G
A
C
0502
A
G
A
C
0704
T
C
A
T
S1
0301
0405
0301
0502
Every time select a SNP
which cover the most pair
Until every pair is covered
then generate a set of tag
SNPs
S2
0301
0704
S3
0405
0502
S4
0405
0704
0502
0704
Method
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Stage1
Set Cover
Stage2
Prediction
Result
Example of TagSNPs(Stage2)
S1
S2
S3
S4
S5
S6
HLA-A-0301
C
A
A
A
T
A
HLA-A-0301
C
A
C
C
T
A
HLA-A-0301
C
A
A
A
T
A
HLA-A-0301
C
A
C
C
T
A
HLA-A-0301
C
A
A
A
T
A
HLA-A-0502
C
A
C
A
T
C
A
C
HLA-A-0502
G
T
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
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Stage1
Set Cover
Stage2
Prediction
Result
Prediction
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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
S01
S02
S03
S04
S05
S06 …
HLA-A-0301
C
A
A
T
T
C
...
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
Score:
Match:+1
Dismatch:+0
Prediction example
S10
S26
S39
S03
S08
S89
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
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
S01
S02
S03
S04
S05
S06 …
HLA-A-0301
C
A
A
T
T
C
...
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
Flowchart
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Entropy
Set Cover
Data Propose
Prediction
Result
HLA Region
HLA-A HLA-B HLA-C
HLA-QA HLA-QB HLA-RB
Reference
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http://www.ncbi.nlm.nih.gov/
http://www.hapmap.org/whatishapmap.ht
ml.en
http://www.imflammegn.org