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Interaction Test
When an allele or residual was associated (p < 0.05) with the disease, tests for independence, difference in association, combined action, interaction and linkage disequilibrium (LD) are used to determine the strongest association.
Table 1 Number of individuals with/without (+/-) factor A and/or factor B.
| Factor A | Factor B | Number of Cases | Number of Controls |
|---|---|---|---|
| + | + | x1 | y1 |
| + | - | x2 | y2 |
| - | + | x3 | y3 |
| - | - | x4 | y4 |
Table 2 Summary of the ten tests (2x2 Tables)
| Comparison | a | b | c | d | Test [Number] |
|---|---|---|---|---|---|
| A vs. non-A | x1+x2 | x3+x4 | y1+y2 | y3+y4 | [1] A associated? |
| B vs. non-B | x1+x3 | x2+x4 | y1+y3 | y2+y4 | [2] B associated? |
| ++ vs. -+ | x1 | x3 | y1 | y3 | [3] A associated in B-positives? |
| +- vs. -- | x2 | x4 | y2 | y4 | [4] A associated in B-negatives? |
| ++ vs. +- | x1 | x2 | y1 | y2 | [5] B associated in A-positives? |
| -+ vs. -- | x3 | x4 | y3 | y4 | [6] B associated in A-negatives? |
| +- vs. -+ | x2 | x3 | y2 | y3 | [7] Difference between A and B association? |
| ++ vs. -- | x1 | x4 | y1 | y4 | [8] Combined A-B association? |
| Association A and B in Cases | x1 | x2 | x3 | x4 | [9] Linkage disequilibrium in cases |
| Association A and B in Controls | y1 | y2 | y3 | y4 | [10] Linkage disequilibrium in controls |
Both test 3 and test 4 are significant: A is associated with the disease independently of B.
Both test 5 and test 6 are significant: B is associated with the disease independently of A.
Both test 3 and test 5 are significant: A and B show interaction.
Test 7 is significant: Difference between A and B is associated with the disease.
Test 8 is significant: A and B have combined action.
Test 9 is significant: A and B are in LD in cases.
Test 10 is significant: A and B are in LD in controls.
--file input0.txt [Mandatory]
--interaction [Mandatory]
--test [Default]
--level [Default]
--out output.txt [Default]
--print [Optimal]
--consensus [Optimal, for residual level only]
--digit [Default, for allele level only]
--freq [Default, for allele level only]
Two levels --level residue and --level allele for amino acid and allele test, respectively. Default is --level residue.
Only --test fisher and --test chisq can be used here. Default is --test fisher.
Test of association using two digits, four digits or six digits. When two was used, alleles such as A*02:01 and A*02:06 will be combined as A*02. Default value is 4.
A value between 0 and 1. Only alleles/allele groups have frequency higher than this threshold will be included in association analysis. Default value is 0.
Default value is output.txt.
Specify --print will print all results to screen (still write results to the output file).
When low resolution HLA typing was used in the input file, the program takes the consensus string of all possible high-resolution HLA typings, marking polymorphic amino acid positions as unknown.
python PyHLA.py --file input0.txt --interaction --consensus
By default, Fisher's exact test was used. Each ID contains three parts: gene, position and residue. OR is the odds ratio calculated with Haldane's correction of Woolf's method. P3-P10 and OR3-OR10 are the p-value and odds ratio for tests listed in table 2, respectively.
ID1 ID2 P3 P4 P5 P6 P7 P8 P9 P10 OR3 OR4 OR5 OR6 OR7 OR8 OR9 OR10
A_57_P B_45_T 0.3897 0.0365 0.0456 1.0000 0.4365 0.0234 1.0000 1.0000 4.71 11.64 1.21 3.00 3.88 14.14 0.58 1.44
A_57_P B_62_G 1.0000 0.0148 0.0473 1.0000 1.0000 0.0076 1.0000 1.0000 1.69 14.61 1.27 11.00 1.33 18.59 0.23 1.97
A_57_P B_65_R 1.0000 0.0148 0.0473 1.0000 1.0000 0.0076 1.0000 1.0000 1.69 14.61 1.27 11.00 1.33 18.59 0.23 1.97
A_57_P B_66_N 1.0000 0.0148 0.0473 1.0000 1.0000 0.0076 1.0000 1.0000 1.69 14.61 1.27 11.00 1.33 18.59 0.23 1.97
A_57_P B_67_M 1.0000 0.0148 0.0473 1.0000 1.0000 0.0076 1.0000 1.0000 1.69 14.61 1.27 11.00 1.33 18.59 0.23 1.97
A_57_P B_67_Y 0.2025 0.0646 0.0330 1.0000 0.1607 0.0913 1.0000 1.0000 6.14 10.49 0.82 1.40 7.49 8.59 0.61 1.04
A_57_P B_70_Q 0.2025 0.0646 0.0330 1.0000 0.1607 0.0913 1.0000 1.0000 6.14 10.49 0.82 1.40 7.49 8.59 0.61 1.04
A_57_P B_70_S 1.0000 0.0148 0.0473 1.0000 1.0000 0.0076 1.0000 1.0000 1.69 14.61 1.27 11.00 1.33 18.59 0.23 1.97
A_57_P B_74_D 0.1988 0.0636 0.0363 1.0000 0.1590 0.0888 1.0000 1.0000 6.24 10.59 0.82 1.40 7.56 8.73 0.78 1.33
A_57_P B_77_S 0.0146 1.0000 0.0490 1.0000 0.0071 1.0000 1.0000 1.0000 14.67 1.74 0.77 0.09 19.13 1.33 5.57 0.66
A_57_P B_80_I 1.0000 0.0162 0.0148 1.0000 1.0000 0.0080 1.0000 0.3334 1.65 14.16 1.28 11.00 1.29 18.12 0.46 3.98
A_57_P B_80_N 0.0346 0.3667 0.0279 1.0000 0.0186 0.4307 1.0000 0.5405 11.91 5.22 0.76 0.33 15.65 3.97 4.53 1.98
A_57_P B_82_R 0.0346 0.3667 0.0279 1.0000 0.0186 0.4307 1.0000 0.5405 11.91 5.22 0.76 0.33 15.65 3.97 4.53 1.98
A_57_P B_83_G 0.0346 0.3667 0.0279 1.0000 0.0186 0.4307 1.0000 0.5405 11.91 5.22 0.76 0.33 15.65 3.97 4.53 1.98
A_57_P B_152_V 0.0347 0.3631 0.0228 1.0000 0.0179 0.4312 1.0000 0.5309 11.89 5.30 0.75 0.33 15.89 3.96 4.59 2.04
A_57_P C_1_G 1.0000 0.0129 0.0243 1.0000 1.0000 1.0000 1.0000 1.0000 0.23 15.31 0.17 11.00 1.39 2.54 0.00 0.09
A_57_P C_165_E 1.0000 0.0129 0.0243 1.0000 1.0000 1.0000 1.0000 1.0000 0.23 15.31 0.17 11.00 1.39 2.54 0.00 0.09
A_57_P DQA1_25_Y 0.0120 1.0000 0.0219 1.0000 0.0599 1.0000 1.0000 1.0000 15.72 0.98 1.46 0.09 10.74 1.43 12.88 0.80
A_57_P DQB1_14_M 0.0123 1.0000 0.0046 1.0000 0.1487 1.0000 1.0000 1.0000 15.58 0.69 2.06 0.09 7.57 1.42 42.74 1.89
A_57_P DQB1_53_L 0.0287 0.4765 0.0488 1.0000 0.0528 0.4110 1.0000 0.5746 12.91 3.32 1.30 0.33 9.96 4.30 6.97 1.79
...
python PyHLA.py --file input0.txt --interaction --level allele --freq 0.01
By default, Fisher's exact test and 4 digit allele was used.
ID1 ID2 P3 P4 P5 P6 P7 P8 P9 P10 OR3 OR4 OR5 OR6 OR7 OR8 OR9 OR10
A*11:77 B*35:01 1.0000 0.0793 1.0000 0.0595 0.7396 0.4127 0.6210 1.0000 0.39 0.67 0.35 0.59 1.13 0.23 0.44 0.76
A*11:77 B*58:01 0.8144 0.0493 0.3127 0.0879 0.0072 1.0000 0.1053 0.6684 0.87 0.61 1.79 1.25 0.49 1.09 1.83 1.28
A*11:77 DQA1*02:01 0.5562 0.1022 0.7598 0.1128 0.6857 0.2500 0.4217 0.3392 0.66 0.68 0.75 0.78 0.87 0.51 1.49 1.54
A*11:77 DRB1*04:66 0.2609 0.1014 1.0000 0.0209 0.0033 0.4209 0.6364 0.5004 0.11 0.69 0.35 2.18 0.32 0.24 0.35 2.20
B*35:01 DQA1*02:01 1.0000 0.0359 1.0000 0.0851 0.3555 0.6945 0.5018 1.0000 0.92 0.56 1.24 0.76 0.74 0.70 1.52 0.92
B*35:01 DRB1*04:66 0.2609 0.0813 1.0000 0.0209 0.0027 0.4214 1.0000 0.3831 0.11 0.62 0.39 2.18 0.28 0.24 0.58 3.20
B*58:01 DQA1*02:01 0.1916 0.1199 1.0000 0.0622 0.0091 0.6062 0.2718 1.0000 1.69 1.23 0.99 0.72 1.70 1.22 1.37 0.99
B*58:01 DRB1*04:66 0.4124 0.0413 1.0000 0.0192 0.1095 1.0000 0.8205 0.3967 0.51 1.29 0.94 2.39 0.54 1.21 0.86 2.19
DQA1*02:01 DRB1*04:66 0.1732 0.1198 1.0000 0.0144 0.0045 0.6998 1.0000 0.1343 0.30 0.79 0.92 2.39 0.33 0.72 1.17 3.05