HAL Id: inserm-02161790
https://www.hal.inserm.fr/inserm-02161790
Submitted on 21 Jun 2019
HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-entific research documents, whether they are pub-lished or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.
L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Easy-HLA : an online software suite to reveal the full details of HLA typing for genetic analyses
Estelle Geffard, Alexandre Walencik, Federico Garnier, Anne Cesbron, Nicolas Vince, Pierre-Antoine Gourraud
To cite this version:
Estelle Geffard, Alexandre Walencik, Federico Garnier, Anne Cesbron, Nicolas Vince, et al.. Easy-HLA : an online software suite to reveal the full details of Easy-HLA typing for genetic analyses. Assises de génétique humaine et médicale 2018, Jan 2018, Nantes, France. �inserm-02161790�
Easy-HLA presentation
HLA-Upgrade validation
A B DRB1 DQB1 (A1,A2) (B15,B17) (DR4,DR7) (DQ3,DQ3) A B DRB1 DQB1 01:01 15:01 04:01 03:02 02:01 57:01 07:01 03:03 A B C DRB1 DQB1 01:01 15:01 03:04 04:01 03:02 02:01 57:01 06:02 07:01 03:03 HLA-2-Haplo :Haplotypes pair prediction
HLA-Upgrade :
High resolution genotype prediction
HLA-Upgrade :
Untyped HLA-C locus prediction
A B C DRB1 DQB1
01:01-57:01-06:02-07:01-03:03 02:01-15:01-03:04-04:01-03:02
http://hla.univ-nantes.fr
Easy-HLA : an online software suite to reveal the full details
of HLA typing for genetic analyses.
Estelle Geffard1,2, Alexandre Walencik1,2,4, Federico Garnier3, Anne Cesbron4, Nicolas Vince1,2, Pierre-Antoine Gourraud1,2
1Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France
2Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
3Agence de la Biomédecine, Saint-Denis La Plaine, France 4EFS Pays de la Loire, Nantes, France
1579 individuals from
European ancestry
917 individuals from African ancestry
In this example, a given HLA serological typing (HLA-A~B~DRB1~DQB1) is processed by Easy-HLA. HLA-Upgrade statistically predicts high resolution typing by leveling-up the HLA genotype and also predict an untyped locus such as HLA-C. HLA-2-Haplo imputes the corresponding haplotypes pair.
HLA-2-Haplo validation
Call rate
Accur
acy EUR AFA
Accur acy Accur acy Genes Genes Accu racy Accur acy Call rate Call rate
The HLA has a pivotal role between clinic and research. The determination of HLA alleles of an individual is required in transplantation. Moreover the HLA is described as associated with countless immune pathologies described by association studies. As the HLA system is the most polymorphic one, both nomenclature and methods constantly refined since the discovery of HLA antigens, leading to difficulties to use old archived typings. We developed a web application called Easy-HLA to facilitate the comprehension of HLA typing. Easy-HLA is based on validated and published HLA haplotypes frequencies. HLA haplotypes frequencies are used to solve typing ambiguities, predict HLA typing of loci (HLA-Upgrade) as well as haplotypes pairs (HLA-2-Haplo) or search for matched HSCT donors (EasyMatch-R). It provides new functional immunogenomics parameters: HLA-Cexpr imputes HLA-C expression, HLA-AA provides amino acid equivalence of HLA alleles and HLA-KIRlig gives KIR ligand classification of HLA alleles.
Our results validate the haplotypes efficiency in predicting high resolution
HLA typing and determining haplotypes pairs. Our tools can be used in
multiple conditions both in clinic and research to: update cohorts, help HSCT donor matching search, bring new parameters for association studies. Both HLA-Upgrade and HLA-2-Haplo show good performance in term of accuracy.
Easy-HLA is tuned to deliver updated HLA information from all HLA typing resolution. These predictions are all done in silico and as such do not require additional typing in the laboratory. Our software will continue improving as we will update our database with additional HLA haplotypes. HLA-Upgrade can predict successfully HLA-A~B~C~DRB1~DQB1 high
resolution typing in different populations from low resolution/partially known
HLA typing. The accuracy of the most probable prediction increases as the call
rate is reduced. The prediction accuracy by locus is on average 10% above for European compared to African-American.
HLA-2-Haplo imputes haplotypes pairs with high confidence: >70% of haplotypes pairs correctly predicted. There is no significant difference of prediction accuracy between population.
HLA-2-Haplo accuracy relies on the number of haplotypes in the database, it performs haplotyping one sample at a time regardless of the input sample size.
prediction accuracy based on call rate
prediction accuracy for each locus
HLA-Upgrade
HLA-2-Haplo
- 2 datasets with high-resolution HLA typing downgraded to low resolution
Low resolution, partial or ambiguous HLA genotype
100 90 80 70 60 50 40 100 90 80 70 100
- Prediction compared to familial determined haplotypes
- 273 individuals from European ancestry and 116 from African ancestry
100 80 60 40 20 0 100 80 60 40 20 0 20 40 60 80 100 20 40 60 80 A B C DRB1 DQB1 A B C DRB1 DQB1 100 100 75 75 50 50 25 0 25 0
Easy-HLA conclusion
Contact : estelle.geffard@univ-nantes.frABDR ABCDR ABCDRDQ
Genotypes input :
