Introduction

MiDAS is a comprehensive R package for immunogenetic data manipulation and statistical analysis. MiDAS recodes input data in the form of HLA alleles and KIR types into biologically meaningful variables, allowing HLA amino acid fine mapping, analyses of HLA evolutionary divergence as well as validated HLA-KIR interactions. Further, it allows comprehensive statistical association analysis workflows with phenotypes of diverse measurement scales. MiDAS thus closes the gap between the inference of immunogenetic variation and its efficient utilization to make relevant discoveries related to T cell, Natural Killer cell, and disease biology.

Quick start

Reading input data

MiDAS includes functions to read HLA and KIR typing data, checking for the correct format and adherence to the right nomenclature. HLA calls can be reduced to a desired resolution when importing it, e.g. from 6-digit to 4-digit. Phenotypic observations can be read e.g. using the read.table function (make sure to include stringsAsFactors = FALSE argument).

pheno_file <- system.file("extdata", "MiDAS_tut_pheno.txt", package = "midasHLA")
pheno <- read.table(pheno_file, header = TRUE, stringsAsFactors = FALSE)
ID disease lab_value outcome
P001 1 -0.85 1
P002 1 -1.60 1
P003 1 -1.04 0
P004 1 -0.92 0
P005 1 -0.42 1
P006 1 -1.53 0
P007 1 0.48 1
P008 1 -1.88 0
P009 1 0.88 0
P010 1 -0.68 0
# HLA calls can be loaded using the readHlaCalls function with the desired resolution
hla_calls_file <- system.file("extdata", "MiDAS_tut_HLA.txt", package = "midasHLA")
hla_calls <- readHlaCalls(hla_calls_file, resolution = 4)
ID A_1 A_2 B_1 B_2 C_1 C_2 DPA1_1 DPA1_2 DPB1_1 DPB1_2 DQA1_1 DQA1_2 DQB1_1 DQB1_2 DRA_1 DRA_2 DRB1_1 DRB1_2
C001 A*25:01 A*26:01 B*07:02 B*18:01 C*12:03 C*07:02 DPA1*01:03 DPA1*01:03 DPB1*02:01 DPB1*04:01 DQA1*05:05 DQA1*01:02 DQB1*06:02 DQB1*03:01 DRA*01:02 DRA*01:02 DRB1*15:01 DRB1*12:01
C002 A*02:01 A*02:324 B*50:01 B*18:01 C*06:02 C*12:03 DPA1*01:03 DPA1*01:03 DPB1*04:02 DPB1*04:02 DQA1*02:01 DQA1*05:05 DQB1*02:02 DQB1*03:01 DRA*01:01 DRA*01:01 DRB1*07:01 DRB1*11:04
C003 A*24:02 A*24:04 B*46:01 B*40:06 C*01:03 C*15:02 DPA1*02:02 DPA1*02:01 DPB1*05:01 DPB1*14:01 DQA1*01:04 DQA1*01:03 DQB1*06:01 DQB1*05:02 DRA*01:02 DRA*01:01 DRB1*14:07 DRB1*08:03
C004 A*01:01 A*24:02 B*08:01 B*15:01 C*07:01 C*03:03 DPA1*01:03 DPA1*01:03 DPB1*04:01 DPB1*03:01 DQA1*01:03 DQA1*01:02 DQB1*06:04 DQB1*06:03 DRA*01:02 DRA*01:01 DRB1*13:01 DRB1*13:02
C005 A*01:01 A*25:01 B*18:01 B*08:01 C*12:03 C*07:01 DPA1*01:03 DPA1*01:03 DPB1*04:01 DPB1*23:01 DQA1*05:01 DQA1*01:02 DQB1*02:01 DQB1*06:02 DRA*01:02 DRA*01:02 DRB1*03:01 DRB1*15:01
C006 A*03:01 A*01:01 B*07:02 B*08:01 C*07:01 C*07:02 DPA1*01:03 DPA1*01:03 DPB1*57:01 DPB1*271:01 DQA1*01:02 DQA1*01:01 DQB1*06:04 DQB1*05:01 DRA*01:01 DRA*01:02 DRB1*13:02 DRB1*01:02
C007 A*01:01 A*02:01 B*15:01 B*08:01 C*07:01 C*03:03 DPA1*02:01 DPA1*01:03 DPB1*04:02 DPB1*13:01 DQA1*05:01 DQA1*03:01 DQB1*02:01 DQB1*03:02 DRA*01:01 DRA*01:02 DRB1*03:01 DRB1*04:01
C008 A*11:01 A*02:01 B*35:01 B*27:05 C*03:04 C*04:01 DPA1*01:03 DPA1*01:03 DPB1*04:01 DPB1*04:01 DQA1*03:03 DQA1*01:02 DQB1*06:04 DQB1*03:01 DRA*01:02 DRA*01:01 DRB1*13:02 DRB1*04:01
C009 A*23:01 A*01:01 B*13:02 B*18:01 C*07:01 C*07:02 DPA1*02:01 DPA1*01:03 DPB1*01:01 DPB1*04:02 DQA1*05:05 DQA1*03:01 DQB1*03:01 DQB1*03:02 DRA*01:01 DRA*01:01 DRB1*11:04 DRB1*04:03
C010 A*31:01 A*02:06 B*15:01 B*56:01 C*04:01 C*03:03 DPA1*02:02 DPA1*02:02 DPB1*05:01 DPB1*05:01 DQA1*03:02 DQA1*03:02 DQB1*03:03 DQB1*03:96 DRA*01:01 DRA*01:01 DRB1*09:01 DRB1*09:01
# KIR calls (currently presence/absence calls, no allele-level resolution) can be loaded using the readKirCalls function
kir_calls_file <- system.file("extdata", "MiDAS_tut_KIR.txt", package = "midasHLA")
kir_calls <- readKirCalls(kir_calls_file)
ID KIR3DL3 KIR2DS2 KIR2DL2 KIR2DL3 KIR2DP1 KIR2DL1 KIR3DP1 KIR2DL4 KIR3DL1 KIR3DS1 KIR2DL5 KIR2DS3 KIR2DS5 KIR2DS4 KIR2DS1 KIR3DL2
C001 1 0 0 1 1 1 1 1 1 0 0 0 0 1 0 1
C002 1 0 0 1 1 1 1 1 1 0 0 0 0 1 0 1
C003 1 0 0 1 1 1 1 1 0 1 1 0 1 0 1 1
C004 1 0 0 1 1 1 1 1 0 1 1 0 1 0 1 1
C005 1 0 0 1 1 1 1 1 1 1 1 0 1 1 1 1
C006 1 0 0 1 1 1 1 1 1 0 0 0 0 1 0 1
C007 1 0 0 1 1 1 1 1 1 0 0 0 0 1 0 1
C008 1 0 0 1 1 1 1 1 1 0 0 0 0 1 0 1
C009 1 1 1 0 1 1 1 1 0 1 1 1 1 0 1 1
C010 1 1 1 1 1 1 1 1 0 1 1 0 1 0 1 1

For convenience, we will here use test data shipped with the package.

HLA <- reduceHlaCalls(MiDAS_tut_HLA, resolution = 4)
KIR <- MiDAS_tut_KIR
pheno <- MiDAS_tut_pheno

Creating midas objects

MiDAS provides the prepareMiDAS function to combine genetic and phenotypic data for subsequent analysis. In this step, it is also possible to infer amino acid level information from HLA calls, encode HLA-KIR interactions, or calculate HLA evolutionary divergence (experiment argument).

midas <- prepareMiDAS(
  hla_calls = HLA,
  kir_calls = KIR,
  colData = pheno,
  experiment = c("hla_alleles", "hla_aa")
  )

MiDAS object

A MiDAS object contains our input data as well as defined transformations. This is an extension of a MultiAssayExperiment and can be handled as such. MiDAS provides some functions to interact with MiDAS objects (check ?MiDAS-class for a full list).

For example, we can explore the HLA alleles frequencies, compare them with published frequencies from the allelefrequencies.net database, and filter out low frequency alleles.

freq <- getFrequencies(
  object = midas,
  carrier_frequency = FALSE,
  experiment = "hla_alleles",
  compare = TRUE
)
term Counts Freq USA NMDP African American pop 2 USA NMDP Chinese USA NMDP European Caucasian USA NMDP Hispanic South or Central American USA NMDP Japanese USA NMDP North American Amerindian USA NMDP South Asian Indian
A*01:01 236 0.1180 0.046700 0.014500 0.1646000 0.072600 0.01000 0.12020 0.154500
A*01:02 2 0.0010 0.004200 NA 0.0001000 0.001400 NA 0.00020 0.000005
A*01:234 1 0.0005 NA NA NA NA NA NA NA
A*01:237 1 0.0005 NA NA NA NA NA NA NA
A*01:274 4 0.0020 NA NA NA NA NA NA NA
A*01:43 1 0.0005 NA NA NA NA NA NA 0.000008
A*01:98 1 0.0005 NA NA NA NA NA NA NA
A*02:01 486 0.2430 0.123500 0.094600 0.2755000 0.209500 0.14800 0.27760 0.049200
A*02:02 2 0.0010 0.041400 0.000100 0.0009000 0.007600 0.00004 0.00140 0.000200
A*02:03 7 0.0035 0.000200 0.077400 0.0000193 0.000200 0.00140 0.00003 0.011000
A*02:05 17 0.0085 0.014900 0.001400 0.0097000 0.014800 0.00060 0.00720 0.010000
A*02:06 22 0.0110 0.000700 0.034900 0.0018000 0.019800 0.07480 0.02750 0.017500
A*02:07 7 0.0035 0.000017 0.094800 0.0000392 0.000055 0.02000 0.00003 0.000600
A*02:08 2 0.0010 0.000001 0.000005 0.0000121 0.000007 NA NA 0.000200
A*02:10 3 0.0015 NA 0.001100 NA NA NA NA 0.000026
A*02:211 1 0.0005 NA NA NA 0.000007 NA 0.00001 NA
A*02:22 1 0.0005 0.000079 0.000030 0.0000640 0.005600 NA 0.00008 0.000013
A*02:324 1 0.0005 NA NA NA NA NA NA NA
A*02:60 1 0.0005 0.000500 NA 0.0000012 0.000017 NA NA NA
A*02:614 1 0.0005 NA NA NA NA NA NA NA
A*02:642 1 0.0005 NA NA NA NA NA NA NA
A*02:686 1 0.0005 NA NA NA NA NA NA NA
A*02:753 1 0.0005 NA NA NA NA NA NA NA
A*02:763 1 0.0005 NA NA NA NA NA NA NA
A*03:01 199 0.0995 0.083900 0.014000 0.1399000 0.073800 0.00900 0.10440 0.063600
A*03:02 13 0.0065 0.000400 0.000600 0.0024000 0.002500 0.00100 0.00150 0.008600
A*03:205 1 0.0005 NA NA NA NA NA NA NA
A*03:24 1 0.0005 0.000005 NA NA NA NA NA NA
A*03:312 3 0.0015 NA NA NA NA NA NA NA
A*03:72 2 0.0010 NA NA NA NA NA NA NA
A*11:01 114 0.0570 0.014200 0.275200 0.0609000 0.045600 0.08740 0.04880 0.139600
A*11:02 1 0.0005 0.000005 0.026300 0.0000056 0.000014 NA NA 0.000100
A*11:03 1 0.0005 0.000008 0.000065 NA 0.000007 NA 0.00001 0.000400
A*11:12 1 0.0005 NA 0.000010 0.0000080 0.000007 NA NA 0.000003
A*11:306 3 0.0015 NA NA NA NA NA NA NA
A*11:43 1 0.0005 NA NA NA NA NA NA NA
A*11:50Q 1 0.0005 NA NA NA NA NA NA NA
A*11:88 3 0.0015 NA NA NA NA NA NA NA
A*23:01 47 0.0235 0.109900 0.002100 0.0197000 0.036800 0.00110 0.01810 0.006600
A*23:17 1 0.0005 NA NA NA NA NA NA NA
A*23:18 1 0.0005 NA NA NA NA NA NA NA
A*24:02 228 0.1140 0.024500 0.151900 0.0846000 0.131600 0.35300 0.12920 0.136200
A*24:03 2 0.0010 0.000400 0.001400 0.0019000 0.004900 0.00010 0.00480 0.006000
A*24:04 1 0.0005 NA 0.000100 NA NA NA NA 0.000038
A*24:07 2 0.0010 0.000500 0.004500 0.0000690 0.000300 0.00070 0.00010 0.011200
A*24:104 2 0.0010 NA NA NA NA NA NA NA
A*24:20 4 0.0020 0.000004 0.001400 0.0000004 NA NA NA 0.000043
A*24:50 4 0.0020 NA NA NA NA NA NA NA
A*24:95 1 0.0005 NA NA 0.0000004 0.000007 NA NA NA
A*25:01 52 0.0260 0.003400 0.000200 0.0210000 0.010100 0.00070 0.01480 0.000100
A*25:09 2 0.0010 NA NA NA NA NA NA NA
A*25:25 1 0.0005 NA NA NA NA NA NA NA
A*26:01 90 0.0450 0.014600 0.023700 0.0309000 0.029500 0.07980 0.01990 0.041800
A*26:02 4 0.0020 0.000005 0.000100 0.0000068 0.000024 NA NA 0.000025
A*26:03 2 0.0010 0.000010 0.000100 0.0000036 0.000034 0.02330 0.00001 0.000014
A*26:08 3 0.0015 0.000100 0.000003 0.0010000 0.000900 NA 0.00090 NA
A*26:16 1 0.0005 NA NA 0.0000002 0.000002 NA NA NA
A*29:01 6 0.0030 0.000300 0.007600 0.0027000 0.002100 0.00030 0.00170 0.013200
A*29:02 45 0.0225 0.031800 0.001000 0.0353000 0.044100 0.00180 0.02740 0.001300
A*29:119 3 0.0015 NA NA NA NA NA NA NA
A*30:01 37 0.0185 0.068500 0.027400 0.0130000 0.019900 0.00190 0.01090 0.017300
A*30:02 44 0.0220 0.066700 0.000300 0.0090000 0.027300 0.00060 0.01160 0.002400
A*30:04 3 0.0015 0.002200 0.000200 0.0015000 0.002500 0.00030 0.00110 0.000200
A*31:01 58 0.0290 0.010000 0.024200 0.0270000 0.043900 0.08490 0.07370 0.033100
A*31:08 1 0.0005 NA NA 0.0000101 NA NA NA NA
A*31:21 1 0.0005 NA NA NA NA NA NA NA
A*32:01 58 0.0290 0.015000 0.006200 0.0355000 0.026100 0.00170 0.02540 0.038600
A*32:02 1 0.0005 NA NA 0.0000028 0.000007 NA NA 0.000003
A*32:116 4 0.0020 NA NA NA NA NA NA NA
A*33:01 20 0.0100 0.020600 0.000500 0.0081000 0.021800 0.00020 0.00660 0.001200
A*33:03 16 0.0080 0.051800 0.101100 0.0032000 0.008200 0.06480 0.00390 0.099200
A*33:05 2 0.0010 0.000013 NA 0.0000986 0.000020 NA 0.00001 NA
A*33:125 1 0.0005 NA NA NA NA NA NA NA
A*33:163 1 0.0005 NA NA NA NA NA NA NA
A*33:51 1 0.0005 NA NA NA NA NA NA NA
A*34:01 1 0.0005 0.000077 0.001100 0.0000398 0.000200 0.00060 0.00020 0.000100
A*34:02 6 0.0030 0.033500 0.000016 0.0009000 0.004600 NA 0.00190 0.000040
A*66:01 10 0.0050 0.014100 0.000200 0.0041000 0.006400 0.00010 0.00320 0.000300
A*68:01 53 0.0265 0.039500 0.004000 0.0319000 0.048000 0.00170 0.03810 0.067600
A*68:02 21 0.0105 0.060300 0.000100 0.0084000 0.024800 0.00030 0.00790 0.000300
A*68:04 1 0.0005 0.000001 NA NA 0.000003 NA NA 0.000003
A*68:16 1 0.0005 NA NA NA 0.000037 NA NA 0.000001
A*68:164 1 0.0005 NA NA NA NA NA NA NA
A*68:17 1 0.0005 0.000011 0.000002 0.0000012 0.000100 NA NA NA
A*68:23 1 0.0005 NA NA 0.0000008 0.000017 NA NA NA
A*68:66 1 0.0005 NA NA NA NA NA NA NA
A*69:01 6 0.0030 0.000200 0.001000 0.0014000 0.002800 0.00008 0.00070 0.000600
A*74:01 2 0.0010 0.054600 0.001400 0.0004000 0.007300 0.00010 0.00230 0.001500
B*07:02 152 0.0760 0.072900 0.007900 0.1306000 0.058400 0.05880 0.10050 0.044000
B*07:04 1 0.0005 0.000008 0.000005 0.0003000 0.000017 0.00002 0.00010 NA
B*07:05 5 0.0025 0.008200 0.008300 0.0030000 0.005200 0.00070 0.00210 0.025000
B*07:06 5 0.0025 NA NA NA NA NA NA NA
B*07:10 1 0.0005 0.000022 NA 0.0000616 0.000007 NA NA 0.000003
B*07:14 1 0.0005 0.000007 0.000005 0.0000286 0.000092 NA NA NA
B*07:22 1 0.0005 0.000002 NA 0.0000052 NA NA NA NA
B*07:47 1 0.0005 NA NA NA NA NA NA NA
B*08:01 128 0.0640 0.037600 0.004600 0.1144000 0.039000 0.00510 0.08220 0.036600
B*08:156 2 0.0010 NA NA NA NA NA NA NA
B*08:94 1 0.0005 NA NA NA NA NA NA NA
B*13:01 5 0.0025 0.000097 0.063500 0.0000961 0.000200 0.01110 0.00020 0.013600
B*13:02 74 0.0370 0.007800 0.029100 0.0239000 0.012800 0.00370 0.01640 0.018400
B*13:117 1 0.0005 NA NA NA NA NA NA NA
B*14:01 22 0.0110 0.007900 0.000200 0.0102000 0.008900 0.00070 0.00790 0.000200
B*14:02 40 0.0200 0.021600 0.001000 0.0286000 0.044100 0.00120 0.02040 0.001700
B*14:28 1 0.0005 NA NA NA NA NA NA NA
B*15:01 86 0.0430 0.010800 0.030000 0.0606000 0.027100 0.07690 0.06160 0.016100
B*15:02 6 0.0030 0.000300 0.064700 0.0000410 0.000300 0.00060 0.00020 0.025600
B*15:03 8 0.0040 0.064000 0.000700 0.0014000 0.012900 0.00010 0.00320 0.000200
B*15:07 2 0.0010 0.000100 0.001600 0.0006000 0.000400 0.00470 0.00690 0.000051
B*15:09 2 0.0010 0.000064 0.000010 0.0002000 0.000700 0.00002 0.00010 0.000200
B*15:10 4 0.0020 0.034600 0.000100 0.0004000 0.005500 0.00020 0.00130 0.000200
B*15:11 3 0.0015 0.000011 0.009100 0.0000084 0.000017 NA NA 0.000064
B*15:12 1 0.0005 0.000001 0.002800 0.0000008 0.000010 NA NA 0.000076
B*15:15 1 0.0005 NA 0.000015 0.0000125 0.004300 0.00008 0.00006 0.000003
B*15:17 10 0.0050 0.004500 0.000800 0.0036000 0.006800 0.00020 0.00220 0.014300
B*15:18 3 0.0015 0.001500 0.009300 0.0026000 0.002100 0.01540 0.00250 0.013500
B*15:20 1 0.0005 0.000004 0.000005 0.0000004 0.000200 NA NA NA
B*15:212 1 0.0005 NA NA NA NA NA NA NA
B*15:220 1 0.0005 NA NA NA NA NA NA NA
B*15:25 3 0.0015 0.000100 0.007400 0.0000072 0.000092 0.00020 0.00006 0.005100
B*15:256 1 0.0005 NA NA NA NA NA NA NA
B*15:27 1 0.0005 NA 0.011200 0.0000036 0.000003 0.00100 0.00003 0.000024
B*15:39 1 0.0005 0.000018 0.000035 0.0000929 0.000700 NA 0.00010 0.000032
B*15:63 1 0.0005 NA 0.000005 0.0000020 0.000027 0.00004 0.00040 NA
B*18:01 129 0.0645 0.032000 0.002600 0.0443000 0.041100 0.00210 0.03230 0.025200
B*18:02 1 0.0005 0.000010 0.001500 0.0000016 0.000010 NA 0.00001 0.000086
B*18:03 1 0.0005 0.000020 0.000005 0.0001000 0.000031 NA 0.00002 NA
B*18:07 1 0.0005 0.000001 NA 0.0000141 0.000002 NA NA 0.000001
B*27:02 9 0.0045 0.000400 0.000070 0.0039000 0.001900 0.00020 0.00280 0.000800
B*27:03 3 0.0015 0.003300 NA 0.0000680 0.000500 NA NA 0.000019
B*27:04 2 0.0010 0.000018 0.019100 0.0000064 0.000027 0.00200 0.00010 0.002000
B*27:05 59 0.0295 0.008400 0.003500 0.0373000 0.016000 0.00230 0.05450 0.008300
B*27:06 1 0.0005 0.000300 0.001000 0.0000056 0.000089 0.00006 0.00001 0.000093
B*27:127 2 0.0010 NA NA NA NA NA NA NA
B*27:14 1 0.0005 0.000032 0.000005 0.0000909 0.000003 NA 0.00040 NA
B*35:01 84 0.0420 0.068900 0.022300 0.0560000 0.071300 0.08690 0.09790 0.062200
B*35:02 14 0.0070 0.000800 0.000700 0.0102000 0.012900 0.00040 0.00450 0.007300
B*35:03 39 0.0195 0.002000 0.007900 0.0162000 0.014700 0.00050 0.00950 0.072000
B*35:05 2 0.0010 0.000400 0.005400 0.0000378 0.005600 0.00050 0.00010 0.000600
B*35:08 15 0.0075 0.000400 0.000500 0.0043000 0.006000 0.00010 0.00150 0.002000
B*35:09 1 0.0005 NA NA 0.0000012 0.000400 NA NA 0.000001
B*35:17 1 0.0005 0.000017 0.000010 0.0000595 0.005100 0.00001 0.00030 0.000008
B*35:194 1 0.0005 NA NA NA NA NA NA NA
B*35:41 1 0.0005 0.000008 NA 0.0000616 0.000003 NA 0.00001 NA
B*35:42 1 0.0005 NA NA NA NA NA NA NA
B*35:43 1 0.0005 0.000092 0.000005 0.0000394 0.018500 NA 0.00020 0.000011
B*35:60 1 0.0005 NA NA NA NA NA NA NA
B*35:67 1 0.0005 NA NA NA NA NA NA NA
B*35:71 1 0.0005 NA NA NA NA NA NA NA
B*37:01 25 0.0125 0.005500 0.006000 0.0144000 0.007500 0.00480 0.01080 0.034100
B*37:68 1 0.0005 NA NA NA NA NA NA NA
B*38:01 53 0.0265 0.002200 0.004100 0.0209000 0.019900 0.00100 0.01020 0.002800
B*38:02 5 0.0025 0.000073 0.040000 0.0000378 0.000200 0.00330 0.00030 0.006900
B*39:01 29 0.0145 0.003200 0.019300 0.0112000 0.007300 0.03030 0.03390 0.005500
B*39:05 1 0.0005 0.000200 0.002000 0.0001000 0.023300 0.00008 0.00090 0.000019
B*39:06 10 0.0050 0.001400 0.000095 0.0064000 0.014600 0.00020 0.01760 0.001100
B*39:09 1 0.0005 0.000012 0.000900 0.0000125 0.002100 0.00004 0.00006 0.000200
B*40:01 58 0.0290 0.012800 0.153800 0.0528000 0.014400 0.06030 0.05180 0.022100
B*40:02 28 0.0140 0.003300 0.017300 0.0126000 0.047800 0.07660 0.03100 0.003000
B*40:06 17 0.0085 0.000400 0.017200 0.0003000 0.001300 0.04450 0.00060 0.091400
B*40:117 1 0.0005 NA 0.000005 NA NA NA NA NA
B*40:21 1 0.0005 NA 0.000002 NA NA NA NA NA
B*40:32 1 0.0005 NA NA 0.0000097 NA NA NA NA
B*40:353 1 0.0005 NA NA NA NA NA NA NA
B*40:49 1 0.0005 NA NA NA NA NA NA NA
B*41:01 9 0.0045 0.003000 0.000400 0.0043000 0.010100 0.00040 0.00280 0.003500
B*41:02 9 0.0045 0.005600 0.000055 0.0050000 0.005200 0.00010 0.00310 0.000600
B*42:01 5 0.0025 0.053100 0.000070 0.0003000 0.006800 0.00006 0.00170 0.000100
B*42:02 2 0.0010 0.007300 0.000025 0.0001000 0.001900 NA 0.00020 0.000016
B*44:02 169 0.0845 0.020800 0.003800 0.0952000 0.040300 0.00750 0.07440 0.008200
B*44:03 87 0.0435 0.045900 0.014000 0.0467000 0.055200 0.06050 0.03780 0.074000
B*44:04 1 0.0005 0.000100 0.000005 0.0006000 0.000300 0.00002 0.00040 0.000001
B*44:05 5 0.0025 0.000300 0.000045 0.0029000 0.001300 0.00010 0.00140 0.000040
B*44:06 1 0.0005 0.000001 NA 0.0000398 0.000041 NA NA 0.000300
B*44:27 10 0.0050 NA NA NA NA NA NA NA
B*44:270 2 0.0010 NA NA NA NA NA NA NA
B*44:37 1 0.0005 NA NA 0.0000004 NA NA NA 0.000005
B*44:55 1 0.0005 NA NA 0.0000004 NA NA NA NA
B*45:01 15 0.0075 0.049500 0.002000 0.0059000 0.017100 0.00040 0.00630 0.000900
B*46:01 11 0.0055 0.000072 0.134300 0.0000752 0.000200 0.04100 0.00010 0.001000
B*47:01 6 0.0030 0.001000 0.000070 0.0027000 0.001800 0.00006 0.00180 0.000600
B*47:04 2 0.0010 NA 0.000005 NA NA NA NA NA
B*48:01 11 0.0055 0.000500 0.013100 0.0007000 0.014200 0.02710 0.01820 0.003700
B*49:01 43 0.0215 0.027900 0.000600 0.0158000 0.025700 0.00050 0.01450 0.006100
B*50:01 31 0.0155 0.008900 0.002700 0.0105000 0.015000 0.00050 0.00790 0.017200
B*50:02 1 0.0005 0.000100 0.000005 0.0004000 0.002000 0.00008 0.00040 0.000008
B*51:01 132 0.0660 0.021700 0.045700 0.0473000 0.060500 0.08900 0.06780 0.074700
B*51:02 1 0.0005 0.000800 0.012200 0.0000696 0.002400 0.00260 0.00760 0.000200
B*51:05 1 0.0005 0.000014 NA 0.0002000 0.000051 0.00002 0.00004 0.000011
B*51:07 4 0.0020 0.000068 0.000800 0.0005000 0.000900 0.00010 0.00030 0.001400
B*51:08 6 0.0030 0.000100 0.000100 0.0012000 0.001800 0.00002 0.00070 0.000900
B*51:09 1 0.0005 0.000700 0.000018 0.0005000 0.000200 0.00007 0.00130 0.000046
B*51:173Q 1 0.0005 NA NA NA NA NA NA NA
B*51:203 1 0.0005 NA NA NA NA NA NA NA
B*51:230 1 0.0005 NA NA NA NA NA NA NA
B*52:01 43 0.0215 0.015400 0.013400 0.0089000 0.020500 0.09900 0.00660 0.074500
B*53:01 8 0.0040 0.117800 0.000300 0.0034000 0.019500 0.00030 0.00730 0.001300
B*54:01 12 0.0060 0.000030 0.030400 0.0000382 0.000092 NA NA 0.000300
B*55:01 32 0.0160 0.004000 0.000800 0.0186000 0.009100 0.00100 0.01430 0.020300
B*55:02 8 0.0040 0.000066 0.027600 0.0000342 0.000089 0.02720 0.00004 0.000500
B*56:01 17 0.0085 0.002300 0.006100 0.0064000 0.003400 0.00930 0.00440 0.006100
B*56:03 1 0.0005 0.000004 0.001800 0.0000012 0.000003 NA NA 0.000016
B*56:09 1 0.0005 NA 0.000002 NA NA NA NA NA
B*57:01 81 0.0405 0.007100 0.005100 0.0365000 0.015200 0.00130 0.02680 0.067600
B*57:02 7 0.0035 0.003800 0.000015 0.0003000 0.000700 0.00002 0.00020 0.000024
B*57:03 6 0.0030 0.031800 0.000065 0.0007000 0.006200 0.00002 0.00100 0.000200
B*58:01 22 0.0110 0.037800 0.087400 0.0073000 0.014200 0.00760 0.00700 0.042000
B*58:02 5 0.0025 0.042200 0.000035 0.0001000 0.003700 NA 0.00180 0.000057
B*59:01 2 0.0010 0.000007 0.000600 0.0000028 0.000003 0.02240 0.00004 0.000019
B*67:01 1 0.0005 0.000100 0.004100 0.0000652 0.000100 0.00910 0.00010 0.000040
B*73:01 2 0.0010 0.000200 0.000070 0.0004000 0.000700 NA 0.00008 0.000200
C*01:02 100 0.0500 0.007800 0.191500 0.0341000 0.054400 0.17320 0.04920 0.035100
C*01:03 2 0.0010 NA 0.001400 0.0000063 NA NA NA 0.000034
C*01:103 1 0.0005 NA NA NA NA NA NA NA
C*01:22 1 0.0005 NA NA NA 0.000005 NA NA NA
C*01:51 1 0.0005 NA NA 0.0000012 NA NA NA NA
C*02:02 88 0.0440 0.089000 0.003600 0.0435000 0.036700 0.00150 0.05540 0.009300
C*02:06 1 0.0005 0.000006 NA 0.0000140 NA NA 0.00010 NA
C*02:10 8 0.0040 NA NA NA NA NA NA NA
C*02:20 1 0.0005 NA NA NA NA NA NA NA
C*03:02 13 0.0065 0.018500 0.087400 0.0022000 0.004900 0.00760 0.00230 0.041900
C*03:03 82 0.0410 0.012900 0.047300 0.0534000 0.029800 0.14850 0.04170 0.015200
C*03:04 86 0.0430 0.056500 0.116500 0.0749000 0.060200 0.12690 0.10160 0.016200
C*03:05 1 0.0005 0.000042 NA 0.0000211 0.019700 NA 0.00005 NA
C*03:06 1 0.0005 0.000004 NA 0.0000143 0.002600 NA 0.00010 NA
C*03:344 4 0.0020 NA NA NA NA NA NA NA
C*03:39 3 0.0015 NA 0.000020 NA NA NA NA NA
C*03:85 1 0.0005 NA NA NA NA NA NA NA
C*04:01 247 0.1235 0.203700 0.043400 0.1059000 0.175600 0.04040 0.13120 0.136400
C*04:03 3 0.0015 0.000100 0.011200 0.0000748 0.000300 0.00030 0.00030 0.013800
C*04:277 1 0.0005 NA NA NA NA NA NA NA
C*05:01 159 0.0795 0.033600 0.003600 0.0939000 0.057900 0.00720 0.07610 0.008400
C*05:05 1 0.0005 0.000003 NA 0.0000167 NA NA NA NA
C*05:37 1 0.0005 NA NA NA NA NA NA NA
C*06:02 195 0.0975 0.086500 0.044700 0.0932000 0.061400 0.01050 0.06970 0.139100
C*06:09 1 0.0005 0.000051 NA NA 0.000007 NA 0.00004 NA
C*07:01 243 0.1215 0.117000 0.010100 0.1600000 0.102000 0.00730 0.11720 0.103900
C*07:02 219 0.1095 0.071300 0.194400 0.1413000 0.121400 0.12180 0.15100 0.107800
C*07:04 34 0.0170 0.007200 0.006400 0.0154000 0.005500 0.00940 0.01160 0.015500
C*07:18 10 0.0050 NA NA NA NA NA NA NA
C*07:204 1 0.0005 NA NA NA NA NA NA NA
C*07:51 2 0.0010 0.000004 NA 0.0000012 NA NA NA 0.000006
C*07:578 7 0.0035 NA NA NA NA NA NA NA
C*07:615 1 0.0005 NA NA NA NA NA NA NA
C*07:696 2 0.0010 NA NA NA NA NA NA NA
C*08:01 22 0.0110 0.001100 0.104300 0.0004000 0.014900 0.06820 0.02220 0.028300
C*08:02 72 0.0360 0.034000 0.001200 0.0385000 0.052600 0.00190 0.02860 0.001900
C*08:03 9 0.0045 0.000070 0.004000 0.0004000 0.003300 0.01290 0.00440 0.001800
C*12:02 43 0.0215 0.001100 0.030700 0.0087000 0.011600 0.10000 0.00480 0.081300
C*12:03 142 0.0710 0.014900 0.017600 0.0486000 0.041500 0.00190 0.02650 0.049100
C*12:132 1 0.0005 NA NA NA NA NA NA NA
C*12:167 1 0.0005 NA NA NA NA NA NA NA
C*12:28 1 0.0005 NA NA NA NA NA NA NA
C*14:02 29 0.0145 0.016500 0.040600 0.0127000 0.015400 0.07810 0.01350 0.033600
C*14:03 5 0.0025 0.001500 0.004200 0.0000629 0.000200 0.05760 0.00010 0.000077
C*15:02 47 0.0235 0.005400 0.025600 0.0223000 0.039300 0.01960 0.04350 0.107700
C*15:05 12 0.0060 0.013000 0.007400 0.0035000 0.006100 0.00050 0.00200 0.011500
C*15:07 1 0.0005 0.000006 NA 0.0000034 0.000013 NA NA 0.000200
C*15:09 1 0.0005 0.000004 NA 0.0000133 0.001900 NA 0.00020 0.000010
C*16:01 49 0.0245 0.096900 0.000200 0.0338000 0.050300 0.00160 0.02810 0.000700
C*16:02 16 0.0080 0.000200 0.000700 0.0027000 0.003900 0.00010 0.00100 0.027900
C*16:04 4 0.0020 0.000043 0.000200 0.0006000 0.000300 NA 0.00020 0.000300
C*17:01 11 0.0055 0.068100 0.000500 0.0088000 0.020000 0.00070 0.00820 0.003900
C*17:03 10 0.0050 NA NA NA NA NA NA NA
C*18:02 3 0.0015 NA NA NA NA NA NA NA
DPA1*01:03 1522 0.7610 NA NA NA NA NA NA NA
DPA1*01:04 12 0.0060 NA NA NA NA NA NA NA
DPA1*01:05 1 0.0005 NA NA NA NA NA NA NA
DPA1*01:11 1 0.0005 NA NA NA NA NA NA NA
DPA1*02:01 308 0.1540 NA NA NA NA NA NA NA
DPA1*02:02 125 0.0625 NA NA NA NA NA NA NA
DPA1*02:06 9 0.0045 NA NA NA NA NA NA NA
DPA1*02:07 13 0.0065 NA NA NA NA NA NA NA
DPA1*03:01 8 0.0040 NA NA NA NA NA NA NA
DPA1*04:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*01:01 74 0.0370 NA NA NA NA NA NA NA
DPB1*02:01 304 0.1520 NA NA NA NA NA NA NA
DPB1*02:02 30 0.0150 NA NA NA NA NA NA NA
DPB1*03:01 137 0.0685 NA NA NA NA NA NA NA
DPB1*04:01 685 0.3425 NA NA NA NA NA NA NA
DPB1*04:02 202 0.1010 NA NA NA NA NA NA NA
DPB1*05:01 107 0.0535 NA NA NA NA NA NA NA
DPB1*06:01 19 0.0095 NA NA NA NA NA NA NA
DPB1*09:01 20 0.0100 NA NA NA NA NA NA NA
DPB1*10:01 25 0.0125 NA NA NA NA NA NA NA
DPB1*104:01 48 0.0240 NA NA NA NA NA NA NA
DPB1*105:01 14 0.0070 NA NA NA NA NA NA NA
DPB1*107:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*11:01 40 0.0200 NA NA NA NA NA NA NA
DPB1*113:01 2 0.0010 NA NA NA NA NA NA NA
DPB1*124:01 12 0.0060 NA NA NA NA NA NA NA
DPB1*126:01 7 0.0035 NA NA NA NA NA NA NA
DPB1*13:01 51 0.0255 NA NA NA NA NA NA NA
DPB1*131:01 2 0.0010 NA NA NA NA NA NA NA
DPB1*133:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*135:01 6 0.0030 NA NA NA NA NA NA NA
DPB1*138:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*14:01 39 0.0195 NA NA NA NA NA NA NA
DPB1*15:01 13 0.0065 NA NA NA NA NA NA NA
DPB1*150:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*158:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*16:01 10 0.0050 NA NA NA NA NA NA NA
DPB1*162:01 5 0.0025 NA NA NA NA NA NA NA
DPB1*17:01 49 0.0245 NA NA NA NA NA NA NA
DPB1*18:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*19:01 7 0.0035 NA NA NA NA NA NA NA
DPB1*20:01 7 0.0035 NA NA NA NA NA NA NA
DPB1*21:01 4 0.0020 NA NA NA NA NA NA NA
DPB1*22:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*23:01 15 0.0075 NA NA NA NA NA NA NA
DPB1*234:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*259:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*271:01 4 0.0020 NA NA NA NA NA NA NA
DPB1*294:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*33:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*350:01 7 0.0035 NA NA NA NA NA NA NA
DPB1*351:01 3 0.0015 NA NA NA NA NA NA NA
DPB1*36:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*38:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*398:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*40:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*41:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*414:01 7 0.0035 NA NA NA NA NA NA NA
DPB1*45:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*461:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*462:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*463:01 4 0.0020 NA NA NA NA NA NA NA
DPB1*47:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*51:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*519:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*547:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*57:01 3 0.0015 NA NA NA NA NA NA NA
DPB1*651:01 4 0.0020 NA NA NA NA NA NA NA
DPB1*702:01 7 0.0035 NA NA NA NA NA NA NA
DPB1*744:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*80:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*88:01 1 0.0005 NA NA NA NA NA NA NA
DPB1*92:01 1 0.0005 NA NA NA NA NA NA NA
DQA1*01:01 192 0.0960 NA NA NA NA NA NA NA
DQA1*01:02 358 0.1790 NA NA NA NA NA NA NA
DQA1*01:03 150 0.0750 NA NA NA NA NA NA NA
DQA1*01:04 52 0.0260 NA NA NA NA NA NA NA
DQA1*01:05 25 0.0125 NA NA NA NA NA NA NA
DQA1*01:06 1 0.0005 NA NA NA NA NA NA NA
DQA1*01:10 2 0.0010 NA NA NA NA NA NA NA
DQA1*02:01 256 0.1280 NA NA NA NA NA NA NA
DQA1*03:01 163 0.0815 NA NA NA NA NA NA NA
DQA1*03:02 31 0.0155 NA NA NA NA NA NA NA
DQA1*03:03 132 0.0660 NA NA NA NA NA NA NA
DQA1*04:01 58 0.0290 NA NA NA NA NA NA NA
DQA1*04:02 2 0.0010 NA NA NA NA NA NA NA
DQA1*05:01 222 0.1110 NA NA NA NA NA NA NA
DQA1*05:03 20 0.0100 NA NA NA NA NA NA NA
DQA1*05:05 305 0.1525 NA NA NA NA NA NA NA
DQA1*05:06 1 0.0005 NA NA NA NA NA NA NA
DQA1*05:07 1 0.0005 NA NA NA NA NA NA NA
DQA1*05:08 1 0.0005 NA NA NA NA NA NA NA
DQA1*05:09 6 0.0030 NA NA NA NA NA NA NA
DQA1*06:01 22 0.0110 NA NA NA NA NA NA NA
DQB1*02:01 218 0.1090 NA NA NA 0.178000 NA NA NA
DQB1*02:02 201 0.1005 NA NA NA NA NA NA NA
DQB1*02:10 1 0.0005 NA NA NA NA NA NA NA
DQB1*03:01 403 0.2015 NA NA NA 0.192700 NA NA NA
DQB1*03:02 169 0.0845 NA NA NA 0.194400 NA NA NA
DQB1*03:03 78 0.0390 NA NA NA 0.021600 NA NA NA
DQB1*03:04 7 0.0035 NA NA NA 0.001400 NA NA NA
DQB1*03:05 3 0.0015 NA NA NA 0.000200 NA NA NA
DQB1*03:19 11 0.0055 NA NA NA NA NA NA NA
DQB1*03:22 22 0.0110 NA NA NA NA NA NA NA
DQB1*03:251 2 0.0010 NA NA NA NA NA NA NA
DQB1*03:96 5 0.0025 NA NA NA NA NA NA NA
DQB1*04:01 26 0.0130 NA NA NA NA NA NA NA
DQB1*04:02 58 0.0290 NA NA NA 0.090300 NA NA NA
DQB1*04:23 3 0.0015 NA NA NA NA NA NA NA
DQB1*05:01 206 0.1030 NA NA NA 0.112200 NA NA NA
DQB1*05:02 68 0.0340 NA NA NA 0.014000 NA NA NA
DQB1*05:03 48 0.0240 NA NA NA 0.019600 NA NA NA
DQB1*05:04 4 0.0020 NA NA NA 0.000300 NA NA NA
DQB1*05:107 1 0.0005 NA NA NA NA NA NA NA
DQB1*06:01 49 0.0245 NA NA NA 0.011200 NA NA NA
DQB1*06:02 215 0.1075 NA NA NA 0.074800 NA NA NA
DQB1*06:03 113 0.0565 NA NA NA 0.049200 NA NA NA
DQB1*06:04 70 0.0350 NA NA NA 0.030300 NA NA NA
DQB1*06:07 1 0.0005 NA NA NA NA NA NA NA
DQB1*06:09 18 0.0090 NA NA NA 0.009300 NA NA NA
DRA*01:01 1289 0.6445 NA NA NA NA NA NA NA
DRA*01:02 711 0.3555 NA NA NA NA NA NA NA
DRB1*01:01 130 0.0650 0.026500 0.009300 0.0860000 0.044400 0.05840 0.07030 0.032100
DRB1*01:02 38 0.0190 0.039200 0.000700 0.0138000 0.035800 0.00060 0.00950 0.001300
DRB1*01:03 9 0.0045 0.002600 0.000070 0.0123000 0.007900 0.00070 0.01000 0.000049
DRB1*03:01 215 0.1075 0.069900 0.068100 0.1216000 0.069500 0.00680 0.08970 0.074600
DRB1*03:02 4 0.0020 0.063100 0.000035 0.0003000 0.010300 0.00008 0.00210 0.000086
DRB1*03:07 1 0.0005 0.000023 NA 0.0000072 0.000034 NA NA 0.000003
DRB1*04:01 101 0.0505 0.020200 0.005100 0.0878000 0.015000 0.01150 0.06580 0.009000
DRB1*04:02 20 0.0100 0.000800 0.000500 0.0106000 0.014300 0.00050 0.00380 0.006400
DRB1*04:03 36 0.0180 0.001700 0.023100 0.0079000 0.017400 0.02440 0.01130 0.052700
DRB1*04:04 48 0.0240 0.008200 0.008800 0.0388000 0.042100 0.00320 0.05120 0.020100
DRB1*04:05 49 0.0245 0.015300 0.061200 0.0067000 0.024300 0.14720 0.00980 0.007500
DRB1*04:06 8 0.0040 0.000200 0.024800 0.0004000 0.001300 0.02480 0.00020 0.001500
DRB1*04:07 16 0.0080 0.003900 0.000800 0.0112000 0.074800 0.00640 0.04860 0.001300
DRB1*04:08 7 0.0035 0.000600 0.000300 0.0039000 0.001600 0.00006 0.00250 0.002300
DRB1*04:10 2 0.0010 0.000100 0.001500 0.0000591 0.003500 0.01820 0.00160 0.001500
DRB1*04:13 1 0.0005 NA 0.000005 0.0000153 0.000003 NA NA 0.000200
DRB1*04:92 1 0.0005 NA NA NA NA NA NA NA
DRB1*07:01 249 0.1245 0.101100 0.053100 0.1342000 0.109000 0.00940 0.10060 0.169500
DRB1*08:01 32 0.0160 0.003700 0.000200 0.0232000 0.012000 0.00080 0.01560 0.003200
DRB1*08:02 14 0.0070 0.000900 0.005500 0.0008000 0.055600 0.04340 0.01580 0.005100
DRB1*08:03 18 0.0090 0.000400 0.068000 0.0024000 0.001800 0.07440 0.00170 0.007100
DRB1*08:04 9 0.0045 0.054200 0.000100 0.0020000 0.009400 0.00020 0.03070 0.000800
DRB1*08:06 2 0.0010 0.005400 0.000010 0.0002000 0.000800 NA 0.00020 NA
DRB1*08:11 1 0.0005 0.000800 0.000002 0.0001000 0.000007 NA 0.00700 NA
DRB1*08:18 1 0.0005 NA NA 0.0000024 0.000024 NA NA 0.000011
DRB1*08:40 1 0.0005 NA NA NA NA NA NA NA
DRB1*08:77 7 0.0035 NA NA NA NA NA NA NA
DRB1*09:01 32 0.0160 0.029700 0.155400 0.0103000 0.017600 0.13870 0.02720 0.009400
DRB1*10:01 22 0.0110 0.019200 0.013400 0.0085000 0.018100 0.00400 0.00690 0.062800
DRB1*11:01 137 0.0685 0.085400 0.062600 0.0556000 0.044300 0.02580 0.04350 0.059800
DRB1*11:02 8 0.0040 0.038800 0.000060 0.0028000 0.011300 0.00010 0.00440 0.000070
DRB1*11:03 12 0.0060 0.000700 0.000095 0.0061000 0.003400 0.00010 0.00330 0.000200
DRB1*11:04 93 0.0465 0.005800 0.002500 0.0295000 0.028000 0.00120 0.01630 0.019700
DRB1*11:14 1 0.0005 0.000074 NA 0.0000893 0.000100 NA 0.00007 0.000005
DRB1*12:01 38 0.0190 0.038200 0.034200 0.0164000 0.010900 0.03750 0.01330 0.006000
DRB1*12:02 18 0.0090 0.002900 0.115000 0.0002000 0.000800 0.01710 0.00030 0.029900
DRB1*12:10 2 0.0010 NA NA NA NA NA NA NA
DRB1*13:01 105 0.0525 0.054200 0.007800 0.0563000 0.047800 0.00760 0.04270 0.067300
DRB1*13:02 89 0.0445 0.073000 0.024200 0.0488000 0.042100 0.05750 0.03790 0.033700
DRB1*13:03 26 0.0130 0.032600 0.000200 0.0109000 0.013300 0.00050 0.00930 0.001300
DRB1*13:05 4 0.0020 0.000300 0.000010 0.0025000 0.003600 0.00004 0.00090 0.000032
DRB1*13:12 2 0.0010 0.000006 0.008100 0.0000008 0.000055 NA NA 0.000097
DRB1*13:27 1 0.0005 0.000020 NA 0.0000020 NA NA NA 0.000005
DRB1*14:01 7 0.0035 0.018600 0.033300 0.0261000 0.019000 0.03010 0.02750 0.011300
DRB1*14:02 3 0.0015 0.000800 0.000200 0.0003000 0.025600 0.00020 0.06350 0.000400
DRB1*14:03 2 0.0010 NA 0.002500 0.0000221 0.000007 NA NA 0.000089
DRB1*14:04 3 0.0015 0.000500 0.005100 0.0007000 0.000800 0.00020 0.00120 0.071300
DRB1*14:05 2 0.0010 0.000025 0.022800 0.0000294 0.000051 0.02420 0.00002 0.000900
DRB1*14:06 6 0.0030 0.000100 0.000200 0.0002000 0.017300 0.01420 0.00290 0.000500
DRB1*14:07 1 0.0005 0.000062 0.001000 0.0002000 0.000200 0.00090 0.00020 0.001500
DRB1*14:18 1 0.0005 0.000001 0.001100 0.0000004 NA NA NA 0.000011
DRB1*14:54 40 0.0200 NA NA NA NA NA NA NA
DRB1*15:01 228 0.1140 0.028200 0.101200 0.1346000 0.059200 0.08670 0.10410 0.090200
DRB1*15:02 37 0.0185 0.002300 0.026600 0.0072000 0.011100 0.09670 0.00450 0.107300
DRB1*15:03 4 0.0020 0.116600 0.000025 0.0005000 0.013700 0.00006 0.00270 0.000200
DRB1*16:01 39 0.0195 0.002000 0.000400 0.0143000 0.010500 0.00030 0.00840 0.000600
DRB1*16:02 5 0.0025 0.013800 0.043500 0.0015000 0.022000 0.00670 0.02910 0.006700
DRB1*16:15 10 0.0050 NA NA NA NA NA NA NA
DRB1*16:32 1 0.0005 NA NA NA NA NA NA NA
DRB1*16:42 1 0.0005 NA NA NA NA NA NA NA
midas <-
  filterByFrequency(
    object = midas,
    experiment = "hla_alleles",
    lower_frequency_cutoff = 0.01
    )

Association analysis

Model definition

Before the actual analysis can be run, we still need to define a statistical model we would like to use. We can use most of the statistical models available in R, such as lm, glm, coxme etc. (technically, they need to have a tidy method available). MiDAS then provides a wrapper function that will evaluate our model for each HLA allele in our data.

Here we will use a very simple formula disease ~ term, term being a placeholder for each tested HLA allele. This notation is necessary to also allow interaction tests (e.g. disease ~ lab_value:term) and also works with other appropriate operations.

midas has to be passed as a data argument to our statistical function, here glm.

# Logistic regression
object <- glm(disease ~ term, data = midas, family = binomial(link = "logit"))

Running analysis

To run our analysis, we will use the runMiDAS function. This function offers multiple analysis scenarios which can be tuned using conditional and omnibus arguments. It can also pre-filter input data based on frequency (check ?runMiDAS to learn more).

results <-
  runMiDAS(
    object = object,
    experiment = "hla_alleles",
    inheritance_model = "dominant",
    conditional = FALSE,
    omnibus = FALSE,
    lower_frequency_cutoff = 0.05
    )

kableResults(results)
MiDAS analysis results
allele p.value p.adjusted estimate std.error conf.low conf.high statistic Ntotal Ntotal [%] N(disease=0) N(disease=0) [%] N(disease=1) N(disease=1) [%]
DQB1*06:02 2.600e-06 1.184e-04 7.756e-01 0.1651 4.552e-01 1.103e+00 4.698e+00 198 9.90% 69 6.90% 129 12.90%
DRB1*15:01 7.300e-06 3.303e-04 7.251e-01 0.1617 4.109e-01 1.046e+00 4.484e+00 206 10.30% 74 7.40% 132 13.20%
C*07:02 1.859e-04 8.367e-03 6.003e-01 0.1606 2.877e-01 9.181e-01 3.737e+00 204 10.20% 78 7.80% 126 12.60%
B*18:01 6.012e-04 2.705e-02 -6.903e-01 0.2012 -1.092e+00 -3.011e-01 -3.431e+00 122 6.10% 79 7.90% 43 4.30%
DRA*01:02 2.701e-03 1.216e-01 3.855e-01 0.1285 1.341e-01 6.379e-01 3.000e+00 573 28.65% 263 26.30% 310 31.00%
DQB1*02:02 4.569e-03 2.056e-01 -4.689e-01 0.1654 -7.957e-01 -1.467e-01 -2.836e+00 185 9.25% 110 11.00% 75 7.50%
B*51:01 4.863e-03 2.188e-01 5.465e-01 0.1941 1.697e-01 9.320e-01 2.816e+00 128 6.40% 49 4.90% 79 7.90%
DRA*01:01 1.073e-02 4.826e-01 -4.765e-01 0.1867 -8.466e-01 -1.132e-01 -2.552e+00 862 43.10% 445 44.50% 417 41.70%
B*44:02 2.068e-02 9.306e-01 4.030e-01 0.1742 6.344e-02 7.472e-01 2.314e+00 161 8.05% 67 6.70% 94 9.40%
DRB1*11:01 3.188e-02 1.000e+00 -4.078e-01 0.1900 -7.841e-01 -3.770e-02 -2.146e+00 131 6.55% 77 7.70% 54 5.40%
DRB1*07:01 3.518e-02 1.000e+00 -3.194e-01 0.1517 -6.181e-01 -2.303e-02 -2.106e+00 228 11.40% 128 12.80% 100 10.00%
DPB1*04:01 6.596e-02 1.000e+00 2.337e-01 0.1271 -1.519e-02 4.832e-01 1.839e+00 539 26.95% 255 25.50% 284 28.40%
B*08:01 8.299e-02 1.000e+00 -3.383e-01 0.1951 -7.243e-01 4.218e-02 -1.734e+00 122 6.10% 70 7.00% 52 5.20%
DQA1*01:02 9.218e-02 1.000e+00 2.275e-01 0.1351 -3.697e-02 4.929e-01 1.684e+00 327 16.35% 151 15.10% 176 17.60%
B*07:02 1.037e-01 1.000e+00 2.969e-01 0.1825 -5.937e-02 6.571e-01 1.627e+00 142 7.10% 62 6.20% 80 8.00%
DRB1*03:01 1.102e-01 1.000e+00 -2.566e-01 0.1606 -5.729e-01 5.751e-02 -1.597e+00 194 9.70% 107 10.70% 87 8.70%
DQA1*02:01 1.177e-01 1.000e+00 -2.341e-01 0.1496 -5.284e-01 5.863e-02 -1.565e+00 235 11.75% 128 12.80% 107 10.70%
C*07:01 1.309e-01 1.000e+00 -2.291e-01 0.1517 -5.275e-01 6.762e-02 -1.511e+00 226 11.30% 123 12.30% 103 10.30%
DQB1*02:01 1.314e-01 1.000e+00 -2.408e-01 0.1596 -5.551e-01 7.133e-02 -1.509e+00 197 9.85% 108 10.80% 89 8.90%
DQA1*01:01 1.613e-01 1.000e+00 2.319e-01 0.1656 -9.190e-02 5.581e-01 1.401e+00 179 8.95% 81 8.10% 98 9.80%
DQB1*03:01 1.699e-01 1.000e+00 -1.797e-01 0.1309 -4.368e-01 7.671e-02 -1.373e+00 373 18.65% 197 19.70% 176 17.60%
A*02:01 1.796e-01 1.000e+00 1.718e-01 0.1280 -7.893e-02 4.229e-01 1.342e+00 427 21.35% 203 20.30% 224 22.40%
DQA1*05:05 2.041e-01 1.000e+00 -1.795e-01 0.1414 -4.573e-01 9.730e-02 -1.270e+00 278 13.90% 148 14.80% 130 13.00%
A*11:01 2.223e-01 1.000e+00 -2.501e-01 0.2049 -6.550e-01 1.501e-01 -1.220e+00 108 5.40% 60 6.00% 48 4.80%
DPA1*01:03 2.340e-01 1.000e+00 2.863e-01 0.2406 -1.828e-01 7.639e-01 1.190e+00 924 46.20% 457 45.70% 467 46.70%
DQA1*05:01 2.369e-01 1.000e+00 -1.871e-01 0.1582 -4.982e-01 1.225e-01 -1.183e+00 201 10.05% 108 10.80% 93 9.30%
DPB1*04:02 2.921e-01 1.000e+00 -1.712e-01 0.1625 -4.910e-01 1.469e-01 -1.054e+00 187 9.35% 100 10.00% 87 8.70%
A*03:01 2.960e-01 1.000e+00 1.685e-01 0.1612 -1.471e-01 4.855e-01 1.045e+00 191 9.55% 89 8.90% 102 10.20%
DPA1*02:02 2.968e-01 1.000e+00 2.190e-01 0.2099 -1.912e-01 6.337e-01 1.043e+00 102 5.10% 46 4.60% 56 5.60%
DQA1*03:01 2.986e-01 1.000e+00 1.807e-01 0.1738 -1.594e-01 5.229e-01 1.040e+00 158 7.90% 73 7.30% 85 8.50%
DQA1*01:03 3.208e-01 1.000e+00 1.798e-01 0.1811 -1.746e-01 5.366e-01 9.928e-01 143 7.15% 66 6.60% 77 7.70%
C*12:03 5.147e-01 1.000e+00 -1.215e-01 0.1865 -4.886e-01 2.438e-01 -6.516e-01 133 6.65% 70 7.00% 63 6.30%
DRB1*01:01 5.622e-01 1.000e+00 -1.121e-01 0.1934 -4.930e-01 2.669e-01 -5.795e-01 122 6.10% 64 6.40% 58 5.80%
DQB1*03:02 6.084e-01 1.000e+00 8.756e-02 0.1709 -2.474e-01 4.235e-01 5.123e-01 164 8.20% 79 7.90% 85 8.50%
DPA1*02:01 6.217e-01 1.000e+00 -6.961e-02 0.1410 -3.464e-01 2.068e-01 -4.935e-01 279 13.95% 143 14.30% 136 13.60%
DPB1*03:01 7.087e-01 1.000e+00 -6.984e-02 0.1869 -4.374e-01 2.967e-01 -3.736e-01 132 6.60% 68 6.80% 64 6.40%
DPB1*02:01 7.233e-01 1.000e+00 -5.016e-02 0.1417 -3.281e-01 2.275e-01 -3.541e-01 275 13.75% 140 14.00% 135 13.50%
A*24:02 7.586e-01 1.000e+00 4.725e-02 0.1537 -2.541e-01 3.490e-01 3.074e-01 216 10.80% 106 10.60% 110 11.00%
C*05:01 7.899e-01 1.000e+00 -4.732e-02 0.1776 -3.963e-01 3.011e-01 -2.664e-01 149 7.45% 76 7.60% 73 7.30%
DQB1*06:03 8.385e-01 1.000e+00 4.153e-02 0.2038 -3.585e-01 4.423e-01 2.038e-01 108 5.40% 53 5.30% 55 5.50%
DQB1*05:01 8.724e-01 1.000e+00 2.578e-02 0.1606 -2.892e-01 3.410e-01 1.606e-01 192 9.60% 95 9.50% 97 9.70%
DQA1*03:03 9.248e-01 1.000e+00 -1.780e-02 0.1887 -3.885e-01 3.526e-01 -9.434e-02 129 6.45% 65 6.50% 64 6.40%
C*06:02 9.348e-01 1.000e+00 -1.338e-02 0.1636 -3.344e-01 3.075e-01 -8.178e-02 183 9.15% 92 9.20% 91 9.10%
C*04:01 9.396e-01 1.000e+00 1.147e-02 0.1515 -2.856e-01 3.086e-01 7.573e-02 225 11.25% 112 11.20% 113 11.30%
A*01:01 1.000e+00 1.000e+00 0.000e+00 0.1522 -2.985e-01 2.985e-01 0.000e+00 222 11.10% 111 11.10% 111 11.10%