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The HLA, or so-called “Human Leukocyte Antigen”, region is the most polymorphic section of the human genome, with 40,623 allelic variants identified across 46 loci. The key roles played by the class I and class II HLA genes in stem-cell therapy and transplantation, disease association research, evolutionary biology, and population genetics result in constant discovery of new allele variants. These data are curated and maintained by the ImmunoPolymorphism Database-IMmunoGeneTics/HLA (IPD-IMGT/HLA) Database and made available on the Anthony Nolan HLA Informatics Group (ANHIG)/IMGTHLA GitHub repository as static text files, which are updated every three months. Standardized use of the data in this key resource can be challenging. To address this, we have developed HLAtools, an R package that automates the consumption of IPD-IMGT/HLA resources, renders them computable, and makes them available alongside tools for data analysis, visualization and investigation. Tthe package is compatible with all IPD-IMGT/HLA Database release versions up to release 3.58.0.
HLAtools version 1.2.0 is available on the CRAN repository at https://cran.r-project.org/package=HLAtools.
Developmental version 1.3.0 of the package (in this repository) can be installed using the xfun::install_github(sjmack/HLAtools) command.
The package includes five data objects that foster computation on IPD-IMGT/HLA resources.
HLAgazeteer, HLAatlas, and alleleListHistory can be updated with each IPD-IMGT/HLA Database release.
In addition, the alignmentFull() function builds the ‘HLAalignments’ object, which includes computable versions of the protein, codon, coding nucleotide and genomic alignments available in the IMGTHLA GitHub repository, as specified by the user. ‘HLAalignments’ is not included the package, but can be built for IPD-IMGT/HLA Database releases 3.00.0 to 3.58.0.
The package includes a suite of functions for dissecting and describing similarities and differences between alleles and across loci.
alleleTrim(allele = "A*03:01:01", resolution = 2)
[1] "A*03:01"
alleleTrim(allele = "A*030101", resolution = 2,version = 2)
[1] "A*0301"
alleles <- c("A*01010102L","DRB1*1613N","HLA-Cw*0322Q")
multiAlleleTrim(alleles,1,2,TRUE)
[1] "A*01L" "DRB1*16N" "HLA-Cw*03Q"
compareSequences(alignType = "gen", alleles = c("DPA1*01:03:01:04","DPA1*01:03:38:01"))
allele_name 51 1544 1723 3318 4149
1 DPA1*01:03:01:04 C A A G C
2 DPA1*01:03:38:01 T G G C G
customAlign("prot",c("DQA1*01:01:01:01","DQB1*05:01:01:01","DPB1*01:01:01:01"),list(1:4,5:8,5:8))
DQA1 1 2 3 4
1 DQA1*01:01:01:01 E D I V
2 DQB1 5 6 7 8
3 DQB1*05:01:01:01 E D F V
4 DPB1 5 6 7 8
5 DPB1*01:01:01:01 E N Y V
customAlign("codon",c("DRB1*01:01","DQB1*02:01","DPB1*01:01"),c(1,2,3,7,8,9,13,14,15))
Allele 1 2 3 7 8 9 13 14 15
1 DRB1*01:01 GGG GAC ACC TTC TTG TGG TTT GAA TGT
2 DQB1*02:01 AGA GAC TCT TTC GTG TAC GGC ATG TGC
3 DPB1*01:01 AGG GCC ACT TAC GTG TAC CAG GAA TGC
customAlign("prot",c("DPB1*01:01:01:01","DQA1*01:01:01:01","DQB1*05:01:01:01"),list(19:35,1:4,5:8))
DPB1 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
1 DPB1*01:01:01:01 N G T Q R F L E R Y I Y N R E E Y
2 DQA1 1 2 3 4
3 DQA1*01:01:01:01 E D I V
4 DQB1 5 6 7 8
5 DQB1*05:01:01:01 E D F V
motifMatch("A*-21M~2P","prot")
[1] "A*02:774" "A*11:284" "A*11:417N" "A*68:216N"
motifMatch("A*196G~301A~3046T","gen",FALSE)
[1] "A*01:09"
motifMatch("A*196G~301A~3046T","gen",TRUE)
[1] "A*01:09:01:01" "A*01:09:01:02"
queryRelease("3.30.0","DRB9",FALSE)
[1] 1
queryRelease("3.30.0","DRB9",TRUE)
[1] "DRB9*01:01"
queryRelease("3.31.0","DRB9",FALSE)
[1] 6
queryRelease("1.05.0","304",TRUE)
[1] "A*0304" "A*3304" "B*1304" "Cw*03041" "Cw*03042" "DQB1*0304" "DRB1*0304" "DRB1*1304" "B*5304" "A*2304"
multiQueryRelease("3.58.0",c("DPB","2N"),TRUE)
[1] "DPB1*786:01:02N" "DPB1*401:01:02N"
validateAllele("A*01:01:01:117")
[1] TRUE
validateAllele("A*01:01:01")
A*01:01:01 is not found in version 3.55.0 alignments.
[1] FALSE
verifyAllele("A*01:01:01:01")
[1] TRUE
verifyAllele("A*01:01:01:01",TRUE)
[1] "TRUE" "3.55.0"
verifyAllele("A*010101",TRUE)
[1] "TRUE" "2.09.0"
verifyAllele("A*0101",TRUE)
[1] "TRUE" "1.06.0"
The package includes functions that convert Genotype List (GL) String Codes across IPD/IMGT-HLA Database release versions and nomenclature epochs, inter-convert between GL String and UNIFORMAT formats, and translate data frames and vectors of HLA allele name data across IPD-IMGT/HLA Database release versions.
GLupdate("hla#1.07.0#HLA-B*35011", "2.05.0")
[1] "hla#2.05.0#HLA-B*350101"
GLupdate("hla#2.05.0#HLA-B*350101", "3.05.0")
[1] "hla#3.05.0#HLA-B*35:01:01:01"
GLupdate("hla#3.55.0#HLA-B*44:02:01:01","1.05.0")
[1] "hla#1.05.0#HLA-B*4402"
GLupdate("hla#3.25.0#HLA-A*01:01:01:01/HLA-A*01:02+HLA-A*24:02:01:01","3.55.0")
[1] "hla#3.55.0#HLA-A*01:01:01:01/HLA-A*01:02:01:01+HLA-A*24:02:01:01"
GLupdate("hla#3.25.0#HLA-A*01:01:01:01/HLA-A*01:02+HLA-A*24:02:01:01","1.05.0")
[1] "hla#1.05.0#HLA-A*0101/HLA-A*0102+HLA-A*2402101"
GLStoUNI("HLA-A*02:01/HLA-A*02:02+HLA-A*03:01/HLA-A*03:02")
[1] "A*02:01,A*03:01|A*02:01,A*03:02|A*02:02,A*03:01|A*02:02,A*03:02"
UNItoGLS("A*02:01,A*03:01|A*02:01,A*03:02|A*02:02,A*03:01|A*02:02,A*03:02")
[1] "HLA-A*02:01/HLA-A*02:02+HLA-A*03:01/HLA-A*03:02"
GIANT(c("A*01:01:01:01","DQA1*01:01:01:01"),"3.56.0","3.00.0")
[1] "A*01:01:01:01" "DQA1*01:01:01"
GIANT(c("A*01:01:01:01","DQA1*01:01:01:01"),"3.56.0","2.20.0")
[1] "A*01010101" "DQA1*010101"
GIANT(c("A*01:01:01:01","DQA1*01:01:01:01"),"3.56.0","1.09.0")
[1] "A*01011" "DQA1*0101"
GIANT(sHLAdata,"3.56.0","2.23.0")[1:5,1:14]
Subject Status A A.1 C C.1 B B.1 DRB1 DRB1.1 DQA1 DQA1.1 DQB1 DQB1.1
1 UT900-23 0 <NA> <NA> 010201 020205 1301 180102 160201 0404 050101 050102 030101 0202
2 UT900-24 0 01010101 02010101 0307 0605 1401 390201 0402 160201 040101 050101 060101 030101
3 UT900-25 0 0210 030102 0712 010201 1520 1301 080201 040701 0201 050102 030302 0202
4 UT900-26 0 01010101 0218 0804 120201 350901 4005 090102 080201 030101 0201 0304 030302
5 UT910-01 0 250101 02010101 1507 0307 510103 1401 110101 090102 050102 030101 050301 0304
The package includes three data-analysis functions that accept Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG)-formatted genotype datasets as input.
To facilitate testing and experimentation with these functions, the ‘sHLAdata’ data object is included in the package. This BIGDAWG-formatted HLA genotype data object represents completely synthetic IPD-IMGT/HLA release 3.56.0 HLA-A, -C, -B, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1 genotype data for 24 control subjects and 23 case subjects, and does not represent any true human population.
rr <- relRisk(sHLAdata)
rr$alleles[[1]][c(1,3),]
Locus Variant Status_1 Status_0 RelativeRisk CI.low CI.high p.value Significant
1 A 01:01:01:01 5 7 0.833333333333333 0.411641930809013 1.68701094924813 0.59291160
2 A 02:01:01:01 8 11 0.830409356725146 0.467284553053116 1.4757168736504 0.50779167
3 A 02:10 4 5 0.9 0.419645026972693 1.93020278553833 0.77978869
rr$genotypes[[1]][c(1:3),]
Locus Variant Status_1 Status_0 RelativeRisk CI.low CI.high p.value Significant
1 A 01:01:01:01+02:01:01:01 0 2 0 0 NaN 0.161777420
2 A 01:01:01:01+02:10 1 0 2.0952380 1.5379358 2.85449005 0.306556273
3 A 01:01:01:01+02:18 0 4 0 0 NaN 0.042730188 *
HLA_data.multi.strat <- BDstrat(sHLAdata,c("DRB1*16:02:01:01","DRB1*04:07:01:01","A*25:01:01:01"),15)
HLA_data.multi.strat$`DRB1*16:02:01:01+DRB1*04:07:01:01+A*25:01:01:01-positive`[1:2,1:8]
Subject Status A A.1 C C.1 B B.1
1 UT900-23 0 <NA> <NA> 01:02:01:01 02:10:06 13:01:01:01 18:01:02
2 UT900-24 0 01:01:01:01 02:01:01:01 03:07:01:01 06:05 14:01:01:01 39:02:01:01
HLA_data.multi.strat$`DRB1*16:02:01:01+DRB1*04:07:01:01+A*25:01:01:01-negative`[1:2,1:8]
Subject Status A A.1 C C.1 B B.1
4 UT900-26 0 01:01:01:01 02:18 08:04:01:01 12:02:01 35:09:01:01 40:05:01:01
6 UT910-02 0 02:10 32:04 18:01:01:01 01:02:01:01 78:02:01 13:01:01:01
HLAdata.PP <- BDtoPyPop(sHLAdata,"sHLA",FALSE)
HLAdata.PP$sHLA.neagtive[1:3,1:10]
Subject Status A_1 A_2 C_1 C_2 B_1 B_2 DRB1_1 DRB1_2
1 UT900-23 0 **** **** 01:02:01:01 02:10:06 13:01:01:01 18:01:02 16:02:01:01 04:04:01:01
2 UT900-24 0 01:01:01:01 02:01:01:01 03:07:01:01 06:05 14:01:01:01 39:02:01:01 04:02:01 16:02:01:01
3 UT900-25 0 02:10 03:01:02 07:12 01:02:01:01 15:20 13:01:01:01 08:02:01:01 04:07:01:01
HLAdata.PP$sHLA.positive[1:3,1:10]
Subject Status A_1 A_2 C_1 C_2 B_1 B_2 DRB1_1 DRB1_2
25 UT910-30 1 02:18 02:18 01:02:01:01 03:07:01:01 40:05:01:01 14:01:01:01 11:01:01:01 04:07:01:01
26 UT910-31 1 **** **** 03:07:01:01 **** 14:01:01:01 78:02:01 04:02:01 08:02:01:01
27 UT910-32 1 03:01:02 03:01:02 06:05 03:07:01:01 39:02:01:01 14:01:01:01 08:02:01:01 08:02:01:01
These binaries (installable software) and packages are in development.
They may not be fully stable and should be used with caution. We make no claims about them.